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PAOLO FRIGIO NICHELLI

CULTORE DELLA MATERIA
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Neuroscienze

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Pubblicazioni

2023 - "When You're Smiling": How Posed Facial Expressions Affect Visual Recognition of Emotions [Articolo su rivista]
Benuzzi, Francesca; Ballotta, Daniela; Casadio, Claudia; Zanelli, Vanessa; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Lui, Fausta
abstract

Facial imitation occurs automatically during the perception of an emotional facial expression, and preventing it may interfere with the accuracy of emotion recognition. In the present fMRI study, we evaluated the effect of posing a facial expression on the recognition of ambiguous facial expressions. Since facial activity is affected by various factors, such as empathic aptitudes, the Interpersonal Reactivity Index (IRI) questionnaire was administered and scores were correlated with brain activity. Twenty-six healthy female subjects took part in the experiment. The volunteers were asked to pose a facial expression (happy, disgusted, neutral), then to watch an ambiguous emotional face, finally to indicate whether the emotion perceived was happiness or disgust. As stimuli, blends of happy and disgusted faces were used. Behavioral results showed that posing an emotional face increased the percentage of congruence with the perceived emotion. When participants posed a facial expression and perceived a non-congruent emotion, a neural network comprising bilateral anterior insula was activated. Brain activity was also correlated with empathic traits, particularly with empathic concern, fantasy and personal distress. Our findings support the idea that facial mimicry plays a crucial role in identifying emotions, and that empathic emotional abilities can modulate the brain circuits involved in this process.

2021 - Uncover the Offensive Side of Disparagement Humor: An fMRI Study [Articolo su rivista]
Bartolo, A.; Ballotta, D.; Nocetti, L.; Baraldi, P.; Nichelli, P. F.; Benuzzi, F.
abstract

Disparagement humor is a kind of humor that denigrates, belittles an individual or a social group. In the aim to unveil the offensive side of these kinds of jokes, we have run an event-related fMRI study asking 30 healthy volunteers to judge the level of fun of a series of verbal stimuli that ended with a sentence that was socially inappropriate but funny (disparagement joke -DJ), socially inappropriate but not funny (SI) or neutral (N). Behavioral results showed disparagement jokes are perceived as funny and at the same time offensive. However, the level of offense in DJ is lower than that registered in SI stimuli. Functional data showed that DJ activated the insula, the SMA, the precuneus, the ACC, the dorsal striatum (the caudate nucleus), and the thalamus. These activations suggest that in DJ a feeling of mirth (and/or a desire to laugh) derived from the joke (e.g., SMA and precuneus) and the perception of the jokes’ social inappropriateness (e.g., ACC and insula) coexist. Furthermore, DJ and SI share a common network related to mentalizing and to the processing of negative feelings, namely the medial prefrontal cortex, the putamen and the right thalamus.

2020 - Voxel sensitivity to kinematic and object-related features during action observation [Poster]
Simonelli, Francesca; Handjaras, Giacomo; Benuzzi, Francesca; Bernardi, Giulio; Leo, Andrea; Duzzi, Davide; Cecchetti, Luca; Nichelli, Paolo F.; Porro, Carlo A.; Pietrini, Pietro; Lui, Fausta; Ricciardi, Emiliano
abstract

2019 - “When you’re smiling”: how facial expressions affect visual recognition of emotions [Poster]
Benuzzi, Francesca; Ballotta, Daniela; Porro, Carlo Adolfo; Nichelli, Paolo F.; Lui, Fausta
abstract

Introduction: Facial expressions can elicit simulation in onlookers, and can thus trigger the subjective experience of the same emotion. Moreover, facial muscles activity occurs automatically during the perception of an emotional facial expression (Dimberg and Thunberg, 1998) and preventing it may interfere with the accuracy of emotion recognition (Ponari et al. 2012). However, whether posing a facial expression can shift the perception of ambiguous expressions, and the possible neural basis of this phenomenon, have not been studied. In the present fMRI study we evaluated the effect of posing a facial expression on the recognition of ambiguous emotional faces. Methods: Twenty-six healthy female subjects (mean age 24 + 5,15 years) took part in the experiment. An fMRI event-related paradigm was used. The volunteers were asked to pose a facial expression (happy -H; disgusted –D; neutral -N) according to an emoticon shown on the screen, then to watch a real face expressing an emotion, finally to indicate whether the emotion perceived was happiness (h) or disgust (d). As stimuli, six different ambiguous emotional faces were used; they were a blend of happy and disgusted faces, built from pictures from the Ekman series (Ekman and Friesen, 1976). Three neutral faces (Ekman and Friesen, 1976) were used as controls. The Interpersonal Reactivity Index (IRI, Albiero et al. 2006) questionnaire for empathy was also administered. Functional data were acquired using a Philips Achieva system at 3T and a gradient-echo echo-planar sequence from 30 axial contiguous slices (TR=2000 ms; 326 volumes x 4 sessions; in-plane matrix= 64x64; voxel size: 3x3x4). fMRI analysis was performed using SPM12 (Wellcome Department of Imaging Neuroscience, London, UK). A double statistical threshold (single-voxel statistics and spatial extent) was used to achieve a combined (i.e., corrected for multiple comparisons) significance level of α < 0.05 (3dClustSim AFNI routine). Results: Behavioural results: Posing a disgusted face increased the percentages of d responses (X2=675,2; p< 0.001; Fig. 1a); whereas posing a happy face increased the h responses (X2=119,3; p< 0.001; Fig. 1a) Functional results: Posing happiness and perceiving disgust with respect to posing happiness and perceiving happiness (Hd vs Hh) activated a widespread functional network comprising several left regions (frontal operculum, insula, SMA, medial frontal gyrus, ACC, and basal ganglia, angular gyrus) as well as the right inferior frontal cortex (Figure 1b top). These areas are known to be involved in the a-modal processing of emotions. Posing a neutral face and perceiving happiness with respect to posing a neutral face and perceiving disgust (Nh vs Nd) activated the right posterior insula (Figure 1b bottom). Finally, in several contrasts we found some clusters of increased activity correlating with scores of some subscales of the IRI questionnaire: in particular, high scores in Empathic Concern correlated with the activity of the precuneus in the Ff vs Fd contrast; Fantasy scores correlated with the activity of the right anterior insula within the Df vs Ff contrast and with posterior cingulate and precuneus in the Dd vs Ff contrast. Conclusions: Perceiving a positive, happy face activated the posterior insula, an area consistently activated by pleasurable touch (Morrison, 2016). Behaviourally, posing an emotion shifts the visual perception of ambiguous expressions towards that same emotion. This effect is modulated by the neural system comprising medial and lateral regions of the prefrontal cortex. We can speculate that a cognitive top-down process from the prefrontal cortex could prevent the sensory-motor simulation elicited by the facial expression in being effective on the recognition of others' facial emotions. References Albiero, P. et al. (2006), Contributo all’adattamento italiano dell’Interpersonal Reactivity Inde

2018 - Acute coronary syndrome associated with alemtuzumab infusion in multiple sclerosis [Articolo su rivista]
Ferraro, Diana; Camera, Valentina; Vitetta, Francesca; Zennaro, Mauro; Ciolli, Ludovico; Nichelli, Paolo Frigio; Sola, Patrizia
abstract

no abstract available

2018 - Central pontine myelinolysis and poorly controlled diabetes: MRI’s hints for pathogenesis [Articolo su rivista]
Fasano, Antonio; Cavallieri, Francesco; Mandrioli, Jessica; Chiari, Annalisa; Nichelli, Paolo
abstract

Dear Sir, Central pontine myelinolysis (CPM) is usually associated with a rapid correction of hyponatremia [1, 2]. In a patient with chronic hyponatremia, oligodendrocytes in the pons decrease their inner osmolarity to protect them from swelling. Thereafter, any rapid osmotic shift in the opposite direction caused by the hypertonic fluid can induce the swollen cells to shrink, leading to osmotic demyelination [1, 2]. Typical MRI features in CPM are characterized by cytotoxic edema (DWI hyperintensity and ADC hypointensity) consistent with shrinkage of the pontine cells [3]. We describe a case of CPM due to poorly controlled diabetes with brain MRI features compatible with vasogenic edema (DWI and ADC hyperintensity) that may suggest an extracellular space expansion rather than shrinkage of the pontine cells

2018 - Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study (Journal of Neuro-Oncology, (2016), 128, 1, (157-162), 10.1007/s11060-016-2093-1) [Articolo su rivista]
Franceschi, Enrico; Depenni, Roberta; Paccapelo, Alexandro; Ermani, Mario; Faedi, Marina; Sturiale, Carmelo; Michiara, Maria; Servadei, Franco; Pavesi, Giacomo; Urbini, Benedetta; Pisanello, Anna; Crisi, Girolamo; Cavallo, Michele A.; Dazzi, Claudio; Biasini, Claudia; Bertolini, Federica; Mucciarini, Claudia; Pasini, Giuseppe; Baruzzi, Agostino; Brandes, Alba A.; Baruzzi, A.; Albani, F.; Calbucci, F.; D’Alessandro, R.; Michelucci, R.; Brandes, A.; Eusebi, V.; Ceruti, S.; Fainardi, E.; Tamarozzi, R.; Emiliani, E.; Cavallo, M.; Franceschi, E.; Tosoni, A.; Cavallo, Marino; Fiorica, F.; Valentini, A.; Depenni, R.; Mucciarini, C.; Crisi, G.; Sasso, Enrico; Biasini, C.; Cavanna, L.; Guidetti, D.; Marcello, Norina; Pisanello, A.; Cremonini, A. M.; Guiducci, G.; de Pasqua, S.; Testoni, S.; Agati, R.; Ambrosetto, G.; Bacci, A.; Baldin, E.; Baldrati, A.; Barbieri, E.; Bartolini, Stefano; Bellavista, E.; Bisulli, F.; Bonora, E.; Bunkheila, F.; Carelli, V.; Crisci, M.; Dall’Occa, P.; de Biase, D.; Ferro, S.; Franceschi, C.; Frezza, G.; Grasso, Vincenzo; Leonardi, M.; Marucci, G.; Morandi, L.; Mostacci, B.; Palandri, G.; Pasini, E.; Pastore Trossello, M.; Pession, A.; Poggi, R.; Riguzzi, P.; Rinaldi, R.; Rizzi, S.; Romeo, G.; Spagnolli, F.; Tinuper, P.; Trocino, C.; Dall’Agata, M.; Frattarelli, M.; Gentili, G.; Giovannini, A.; Iorio, P.; Pasquini, U.; Galletti, G.; Guidi, C.; Neri, W.; Patuelli, A.; Strumia, S.; Faedi, M.; Casmiro, M.; Gamboni, A.; Rasi, F.; Cruciani, Giuseppe; Cenni, P.; Dazzi, C.; Guidi, A. R.; Zumaglini, F.; Amadori, A.; Pasini, G.; Pasquinelli, Mario; Pasquini, Elena; Polselli, A.; Ravasio, A.; Viti, B.; Sintini, M.; Ariatti, A.; Bertolini, F.; Bigliardi, G.; Carpeggiani, P.; Cavalleri, F.; Meletti, S.; Nichelli, P.; Pettorelli, E.; Pinna, Greta; Zunarelli, E.; Artioli, F.; Bernardini, I.; Costa, M.; Greco, G.; Guerzoni, R.; Stucchi, C.; Iaccarino, Corrado; Ragazzi, M.; Rizzi, R.; Zuccoli, G.; Api, P.; Cartei, F.; Colella, Margherita; Fallica, E.; Farneti, M.; Frassoldati, A.; Granieri, E.; Latini, F.; Monetti, C.; Saletti, A.; Schivalocchi, R.; Sarubbo, S.; Seraceni, S.; Tola, M. R.; Urbini, B.; Zini, G.; Giorgi, C.; Montanari, E.; Cerasti, D.; Crafa, P.; Dascola, I.; Florindo, I.; Giombelli, E.; Mazza, S.; Ramponi, V.; Servadei, F.; Silini, E. M.; Torelli, P.; Immovilli, P.; Morelli, N.; Vanzo, C.; Nobile, C.
abstract

The members of the PERNO Study Group were not individually captured in the metadata of the original publication. They are included in the metadata of this publication.

2018 - Eight weddings and six funerals: An fMRI study on autobiographical memories [Articolo su rivista]
Benuzzi, F.; Ballotta, D.; Handjaras, G.; Leo, A.; Papale, P.; Zucchelli, M.; Molinari, M. A.; Lui, F.; Cecchetti, L.; Ricciardi, E.; Sartori, G.; Pietrini, P.; Nichelli, P. F.
abstract

“Autobiographical memory” (AM) refers to remote memories from one's own life. Previous neuroimaging studies have highlighted that voluntary retrieval processes from AM involve different forms of memory and cognitive functions. Thus, a complex and widespread brain functional network has been found to support AM. The present functional magnetic resonance imaging (fMRI) study used a multivariate approach to determine whether neural activity within the AM circuit would recognize memories of real autobiographical events, and to evaluate individual differences in the recruitment of this network. Fourteen right-handed females took part in the study. During scanning, subjects were presented with sentences representing a detail of a highly emotional real event (positive or negative) and were asked to indicate whether the sentence described something that had or had not really happened to them. Group analysis showed a set of cortical areas able to discriminate the truthfulness of the recalled events: medial prefrontal cortex, posterior cingulate/retrosplenial cortex, precuneus, bilateral angular, superior frontal gyri, and early visual cortical areas. Single-subject results showed that the decoding occurred at different time points. No differences were found between recalling a positive or a negative event. Our results show that the entire AM network is engaged in monitoring the veracity of AMs. This process is not affected by the emotional valence of the experience but rather by individual differences in cognitive strategies used to retrieve AMs.

2018 - Modulation of neural circuits underlying temporal production by facial expressions of pain [Articolo su rivista]
Ballotta, Daniela; Lui, Fausta; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

2018 - Neural correlates of anosognosia in Alzheimer’s disease and mild cognitive impairment: A multi-method assessment [Articolo su rivista]
Tondelli, M.; Barbarulo, Anna Maria; Vinceti, G.; Vincenzi, Chiara; Chiari, A.; Nichelli, P. F.; Zamboni, G.
abstract

Patients with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) may present anosognosia for their cognitive deficits. Three different methods have been usually used to measure anosognosia in patients with AD and MCI, but no studies have established if they share similar neuroanatomical correlates. The purpose of this study was to investigate if anosognosia scores obtained with the three most commonly used methods to assess anosognosia relate to focal atrophy in AD and MCI patients, in order to improve understanding of the neural basis of anosognosia in dementia. Anosognosia was evaluated in 27 patients (15 MCI and 12 AD) through clinical rating (Clinical Insight Rating Scale, CIRS), patient-informant discrepancy (Anosognosia Questionnaire Dementia, AQ-D), and performance discrepancy on different cognitive domains (self-appraisal discrepancies, SADs). Voxel-based morphometry correlational analyses were performed on magnetic resonance imaging (MRI) data with each anosognosia score. Increasing anosognosia on any anosognosia measurement (CIRS, AQ-D, SADs) was associated with increasing gray matter atrophy in the medial temporal lobe including the right hippocampus. Our results support a unitary mechanism of anosognosia in AD and MCI, in which medial temporal lobes play a key role, irrespectively of the assessment method used. This is in accordance with models suggesting that anosognosia in AD is primarily caused by a decline in mnemonic processes.

2017 - A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment [Articolo su rivista]
Vinceti, Marco; Chiari, Annalisa; Eichmüller, Marcel; Rothman, Kenneth J; Filippini, Tommaso; Malagoli, Carlotta; Weuve, Jennifer; Tondelli, Manuela; Zamboni, Giovanna; Nichelli, Paolo F; Michalke, Bernhard
abstract

Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form.

2017 - Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome [Articolo su rivista]
Ferraro, Diana; Galli, Veronica; Simone, ANNA MARIA; Bedin, Roberta; Vitetta, Francesca; Merelli, Elisa; Nichelli, Paolo Frigio; Sola, Patrizia
abstract

Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.

2017 - Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy [Articolo su rivista]
Baldin, Elisa; Testoni, Stefania; de Pasqua, Silvia; Ferro, Salvatore; Albani, Fiorenzo; Baruzzi, Agostino; D’Alessandro, Roberto; On behalf of PERNO study group, Null; Baruzzi, A.; Albani, F.; Calbucci, F.; D’Alessandro, R.; Michelucci, R.; Brandes, A.; Eusebi, V.; Ceruti, S.; Fainardi, E.; Tamarozzi, R.; Emiliani, E.; Cavallo, M.; Franceschi, E.; Tosoni, A.; Cavallo, M.; Fiorica, F.; Valentini, A.; Depenni, R.; Mucciarini, C.; Crisi, G.; Sasso, E.; Biasini, C.; Cavanna, L.; Guidetti, D.; Marcello, N.; Pisanello, A.; Cremonini, A. M.; Guiducci, G.; de Pasqua, S.; Testoni, S.; Agati, R.; Ambrosetto, G.; Bacci, A.; Baldin, E.; Baldrati, A.; Barbieri, E.; Bartolini, S.; Bellavista, E.; Bisulli, F.; Bonora, E.; Bunkheila, F.; Carelli, V.; Crisci, M.; Dall’Occa, P.; Ferro, S.; Franceschi, C.; Frezza, G.; Grasso, V.; Leonardi, M.; Mostacci, B.; Palandri, G.; Pasini, E.; Pastore Trossello, M.; Poggi, R.; Riguzzi, P.; Rinaldi, R.; Rizzi, S.; Romeo, G.; Spagnolli, F.; Tinuper, P.; Trocino, C.; Dall’Agata, M.; Faedi, M.; Frattarelli, M.; Gentili, G.; Giovannini, A.; Iorio, P.; Pasquini, U.; Galletti, G.; Guidi, C.; Neri, W.; Patuelli, A.; Strumia, S.; Casmiro, M.; Gamboni, A.; Rasi, F.; Cruciani, G.; Cenni, P.; Dazzi, C.; Guidi, A. R.; Zumaglini, F.; Amadori, A.; Pasini, G.; Pasquinelli, M.; Pasquini, E.; Polselli, A.; Ravasio, A.; Viti, B.; Sintini, M.; Ariatti, A.; Bertolini, F.; Bigliardi, G.; Carpeggiani, P.; Cavalleri, F.; Meletti, Stefano; Nichelli, Paolo Frigio; Pettorelli, E.; Pinna, G.; Zunarelli, E.; Artioli, F.; Bernardini, I.; Costa, M.; Greco, G.; Guerzoni, R.; Stucchi, C.; Iaccarino, C.; Ragazzi, M.; Rizzi, R.; Zuccoli, G.; Api, P.; Cartei, F.; Fallica, E.; Granieri, E.; Latini, F.; Lelli, G.; Monetti, C.; Saletti, A.; Schivalocchi, R.; Seraceni, S.; Tola, M. R.; Urbini, B.; Giorgi, C.; Montanari, E.; Cerasti, D.; Crafa, P.; Dascola, I.; Florindo, I.; Giombelli, E.; Mazza, S.; Ramponi, V.; Servadei, F.; Silini, E. M.; Torelli, P.; Immovilli, P.; Morelli, N.; Vanzo, C.; Nobile, C.
abstract

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4–11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3–10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4–0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3–8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.

2017 - Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies [Articolo su rivista]
Galassi, Giuliana; Tondelli, Manuela; Ariatti, Alessandra; Benuzzi, Francesca; Nichelli, Paolo Frigio; Valzania, Franco
abstract

Aim of the study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. Materials and Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.

2017 - Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study [Articolo su rivista]
Rosafio, Francesca; Lelli, Nicoletta; Mimmi, Stefano; Vandelli, Laura; Bigliardi, Guido; Dell'Acqua, Maria Luisa; Picchetto, Livio; Pentore, Roberta; Ferraro, Diana; Trenti, Tommaso; Nichelli, Paolo Frigio; Zini, Andrea
abstract

Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms. Methods: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms. Results: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found. Conclusion: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies.

2017 - Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study [Articolo su rivista]
Agostini, A.; Ballotta, D.; Righi, S.; Moretti, M.; Bertani, A.; Scarcelli, A.; Sartini, A.; Ercolani, M.; Nichelli, P.; Campieri, M.; Benuzzi, F.
abstract

Background: In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. Methods: 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Key Results: Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). Conclusions &amp; Inferences: The MCC integrate “high” emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.

2016 - Cerebrospinal fluid amounts of HLA-G in dimeric form are strongly associated to patients with MRI inactive multiple sclerosis [Articolo su rivista]
Fainardi, Enrico; Bortolotti, Daria; Bolzani, Silvia; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Baldi, Eleonora; Caniatti, Maria Luisa; Casetta, Ilaria; Gentili, Valentina; Granieri, Enrico; Rizzo, Roberta; Tola, M. R.; Dallocchio, F.; Bellini, T.; Rotola, A.; Di Luca, D.; Seraceni, S.; Contini, C.; Sabbioni, S.; Negrini, M.; Tognon, M.; Antonelli, T.; Groppo, E.; Gentile, M.; Ceruti, S.; Manfrinato, M. R.; Trentini, A.; Miotto, E.; Ferracin, M.; Mazzoni, E.; Pietrobon, S.; Masini, I.; Rotondo, J. C.; Martini, F.; Baruzzi, A.; Roberto D'Alessandro, R.; Michelucci, R.; Salvi, F.; Stecchi, S.; Scandellari, C.; Terzano, G.; Granella, F.; Nichelli, Paolo Frigio; Sola, P.; Ferraro, Diana; Vitetta, F.; Simone, ANNA MARIA; Bedin, Roberta; Marcello, N.; Motti, L.; Montepietra, S.; Guidetti, D.; Immovilli, P.; Montanari, E.; Pesci, I.; Guareschi, A.; Greco, G.; Santangelo, M.; Mauro, A. M.; Malagù, S.; Rasi, F.; Spadoni, M.; Galeotti, M.; Fiorani, L.; Neri, W.; Ravasio, A.; Pasquinelli, M.; Gutman, S.; Monaldini, C.
abstract

Background: The relevance of human leukocyte antigen (HLA)-G in dimeric form in multiple sclerosis (MS) is still unknown. Objective: To investigate the contribution of cerebrospinal fluid (CSF) HLA-G dimers in MS pathogenesis. Methods: CSF amounts of 78-kDa HLA-G dimers were measured by western blot analysis in 80 MS relapsing-remitting MS (RRMS) patients and in 81 inflammatory and 70 non-inflammatory controls. Results: CSF amounts of 78kDa HLA-G dimers were more frequent in RRMS than in inflammatory (p<0.01) and non-inflammatory controls (p<0.001) and in magnetic resonance imaging (MRI) inactive than in MRI active RRMS (p<0.00001). Conclusion: Our findings suggest that HLA-G dimers may be implicated in termination of inflammatory response occurring in MS.

2016 - Familial paraganglioma syndrome: a rare cause of carotid artery occlusion [Articolo su rivista]
Rosafio, Francesca; Dell’Acqua, Maria Luisa; Madeo, Bruno; Kara, Elda; Vandelli, Laura; Vallone, Stefano; Bigliardi, Guido; Picchetto, Livio; Nichelli, Paolo Frigio; Zini, Andrea
abstract

We describe the case of a carotid body paraganglioma who was admitted for sudden onset of left-sided throbbing headache and visual impairment. We suggest to follow-up and treat CBPs, in order to avoid not only symptoms due to compressing and secreting effects, but also possible thrombotic complications in case of an aggressive course.

2016 - Serum IgG against Simian Virus 40 antigens are hampered by high levels of sHLA-G in patients affected by inflammatory neurological diseases, as multiple sclerosis [Articolo su rivista]
Rizzo, Roberta; Pietrobon, Silvia; Mazzoni, Elisa; Bortolotti, D.; Martini, Fernanda; Castellazzi, Massimiliano; Casetta, Ilaria; Fainardi, Enrico; Luca, Dario; Granieri, Enrico; Tognon, Mauro; Granieri, E.; Castellazzi, M.; Casetta, I.; Tola, M. R.; Fainardi, E.; Dallocchio, F.; Bellini, T.; Rizzo, R.; Rotola, A.; Di Luca, D.; Seraceni, S.; Contini, C.; Sabbioni, S.; Negrini, M.; Tognon, M.; Antonelli, T.; Groppo, E.; Gentile, M.; Baldi, E.; Caniatti, M. L.; Ceruti, S.; Manfrinato, M. R.; Trentini, A.; Miotto, E.; Ferracin, M.; Mazzoni, E.; Pietrobon, S.; Masini, I.; Rotondo, J. C.; Martini, F.; Baruzzi, A.; Roberto D'Alessandro, R.; Michelucci, R.; Salvi, F.; Stecchi, S.; Scandellari, C.; Terzano, G.; Granella, F.; Nichelli, Paolo Frigio; Sola, P.; Ferraro, Diana; Vitetta, F.; Simone, ANNA MARIA; Bedin, Roberta; Marcello, N.; Motti, L.; Montepietra, S.; Guidetti, D.; Immovilli, P.; Montanari, E.; Pesci, I.; Guareschi, A.; Greco, G.; Santangelo, M.; Mauro, A. M.; Malagù, S.; Rasi, F.; Spadoni, M.; Galeotti, M.; Fiorani, L.; Neri, W.; Ravasio, A.; Pasquinelli, M.; Gutman, S.; Monaldini, C.
abstract

Background: Many investigators detected the simian polyomavirus SV40 footprints in human brain tumors and neurologic diseases and recently it has been indicated that SV40 seems to be associated with multiple sclerosis (MS) disease. Interestingly, SV40 interacts with human leukocyte antigen (HLA) class I molecules for cell entry. HLA class I antigens, in particular non-classical HLA-G molecules, characterized by an immune-regulatory function, are involved in MS disease, and the levels of these molecules are modified according with the disease status. Objective: We investigated in serum samples, from Italian patients affected by MS, other inflammatory diseases (OIND), non-inflammatory neurological diseases (NIND) and healthy subjects (HS), SV40-antibody and soluble sHLA-G and the association between SV40-prevalence and sHLA-G levels. Methods: ELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples. Results: The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of OIND (N = 8/77) and 15 % of NIND (N = 9/59), which is suggestive of a lower prevalence in respect to HS (22 %, N = 18/83). MS patients are characterized by higher sHLA-G serum levels (13.9 ± 0.9 ng/ml; mean ± St. Error) in comparison with OIND (6.7 ± 0.8 ng/ml), NIND (2.9 ± 0.4 ng/ml) and HS (2.6 ± 0.7 ng/ml) subjects. Interestingly, we observed an inverse correlation between SV40 antibody prevalence and sHLA-G serum levels in MS patients. Conclusion: The data obtained showed a low prevalence of SV40 antibodies in MS patients. These results seems to be due to a generalized status of inability to counteract SV40 infection via antibody production. In particular, we hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides.

2016 - The wide spectrum of cerebrotendinous xanthomatosis: Case report of a rare but treatable disease [Articolo su rivista]
Rosafio, Francesca; Cavallieri, Francesco; Guaraldi, Pietro; Taroni, Franco; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive disorder of lipid storage caused by mutations in the CYP27A1 gene, coding for a sterol 27-hydroxylase, leading to increased deposition of cholesterol in multiple tissues. CTX is characterized by the association of early non-neurological manifestations and adult-onset neurological dysfunctions (spastic ataxia, dementia, psychiatric disorders, peripheral neuropathy). Early and long-term treatment with chenodeoxycholic acid (CDCA) can slow down neurological symptoms progression, but diagnosis usually has a delay of several years. We report two Italian siblings having quite different phenotypes associated to a G-to-A transition in the c-1263 terminal causing a splicing alteration. This mutation has not been described before in Italy, and has been reported once in Japan. This case widens the clinical and genetic spectrum of Cerebrotendinous Xantomatosis in Italy and would like to suggest the importance of genetic testing in patients with autosomal recessive spastic paraparesis associated with typical non-neurological symptoms.

2016 - Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study [Articolo su rivista]
Franceschi, Enrico; Depenni, R.; Paccapelo, Alexandro; Ermani, Mario; Faedi, M.; Sturiale, Carmelo; Michiara, Maria; Servadei, F.; Pavesi, Giacomo; Urbini, B.; Pisanello, A.; Crisi, G.; Cavallo, Michele A.; Dazzi, C.; Biasini, C.; Bertolini, F.; Mucciarini, C.; Pasini, G.; Baruzzi, Agostino; Brandes, Alba A; Albani, F.; Calbucci, F.; D’Alessandro, R.; Michelucci, R.; de Pasqua, S.; Testoni, S.; Brandes, A.; Franceschi, E.; Tosoni, A.; Eusebi, V.; Ceruti, S.; Fainardi, E.; Tamarozzi, R.; Emiliani, E.; Cavallo, M.; Fiorica, F.; Sasso, E.; Cavanna, L.; Guidetti, D.; Marcello, N.; Cremonini, A. M.; Guiducci, G.; Agati, R.; Ambrosetto, G.; Bacci, A.; Baldin, E.; Baldrati, A.; Barbieri, E.; Bartolini, S.; Bellavista, E.; Bisulli, F.; Bonora, E.; Bunkheila, F.; Carelli, V.; Crisci, M.; Dall’Occa, P.; de Biase, D.; Ferro, S.; Franceschi, C.; Frezza, G.; Grasso, V.; Leonardi, M.; Marucci, G.; Morandi, L.; Mostacci, B.; Palandri, G.; Pasini, E.; Pastore Trossello, M.; Pession, A.; Poggi, R.; Riguzzi, P.; Rinaldi, R.; Rizzi, S.; Romeo, G.; Spagnolli, F.; Tinuper, P.; Trocino, C.; Dall’Agata, M.; Frattarelli, M.; Gentili, G.; Giovannini, A.; Iorio, P.; Pasquini, U.; Galletti, G.; Guidi, C.; Neri, W.; Patuelli, A.; Strumia, S.; Casmiro, M.; Gamboni, A.; Rasi, F.; Cruciani, G.; Cenni, P.; Guidi, A. R.; Zumaglini, F.; Amadori, A.; Pasquinelli, M.; Pasquini, E.; Polselli, A.; Ravasio, A.; Viti, B.; Sintini, M.; Ariatti, A.; Bigliardi, G.; Carpeggiani, P.; Cavalleri, F.; Meletti, Stefano; Nichelli, Paolo Frigio; Pettorelli, E.; Pinna, G.; Zunarelli, E.; Artioli, F.; Bernardini, I.; Costa, M.; Greco, G.; Guerzoni, R.; Stucchi, C.; Iaccarino, C.; Ragazzi, M.; Rizzi, R.; Zuccoli, G.; Api, P.; Cartei, F.; Colella, M.; Fallica, E.; Farneti, M.; Frassoldati, A.; Granieri, E.; Latini, F.; Monetti, C.; Saletti, A.; Schivalocchi, R.; Sarubbo, S.; Seraceni, S.; Tola, M. R.; Zini, G.; Giorgi, C.; Montanari, E.; Cerasti, D.; Crafa, P.; Dascola, I.; Florindo, I.; Giombelli, E.; Mazza, S.; Ramponi, V.; Silini, E. M.; Torelli, P.; Immovilli, P.; Morelli, N.; Vanzo, C.; Nobile, C.
abstract

The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients &gt;70&nbsp;years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age &gt;70&nbsp;years; PS 0–3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1&nbsp;months (95&nbsp;% CI 8.8–13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6&nbsp;months (95&nbsp;% CI 8.6–14.6), and 9.3&nbsp;months (95&nbsp;% CI 8.1–10.6) in patients treated with RT alone (P&nbsp;=&nbsp;0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2&nbsp;months, 95&nbsp;% CI 11.5–22.9) (P&nbsp;=&nbsp;0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.

2016 - e-NIHSS: an Expanded National Institutes of Health Stroke Scale Weighted for Anterior and Posterior Circulation Strokes [Articolo su rivista]
Olivato, Silvia; Nizzoli, Silvia; Cavazzuti, Milena; Casoni, Federica; Nichelli, Paolo Frigio; Zini, Andrea
abstract

Background The National Institutes of Health Stroke Scale (NIHSS) is the most widespread clinical scale used in patients presenting with acute stroke. The merits of the NIHSS include simplicity, quickness, and agreement between clinicians. The clinical evaluation on posterior circulation stroke remains still a limit of NIHSS. Methods We assessed the application of a new version of NIHSS, the e-NIHSS (expanded NIHSS), adding specific elements in existing items to explore signs/symptoms of a posterior circulation stroke. A total of 22 consecutive patients with suspected vertebrobasilar stroke were compared with 25 patients with anterior circulation stroke using NIHSS and e-NIHSS. Results We compared the NIHSS and e-NIHSS scores obtained by the 2 examiners, in patients with posterior circulation infarct (POCI), using the Wilcoxon test. Patients with POCI evaluated with e-NIHSS had an average of 2 points higher than patients evaluated with classical NIHSS. The difference was statistically significant (P &lt; .05), weighted by the new expanded items. Conclusions The NIHSS is a practical scale model, with high reproducibility between trained, different examiners, focused on posterior circulation strokes, with the same total score and number of items of the existing NIHSS. The e-NHISS could improve the sensitivity of NIHSS in posterior circulation stroke and could have an impact on clinical trials, as well as on outcomes. Further studies are needed to investigate a larger number of patients and the correlation between the e-NIHSS score and neuroimaging findings.

2016 - “Opening the Unopenable”: Endovascular Treatment in a Patient with Three Months' Internal Carotid Artery Occlusion and Hemispheric Symptomatic Hypoperfusion [Articolo su rivista]
Bigliardi, Guido; Dell'Acqua, Maria Luisa; Vallone, Stefano; Barbi, Filippo; Pentore, Roberta; Picchetto, Livio; Carpeggiani, Paolo; Nichelli, Paolo Frigio; Zini, Andrea
abstract

Background Internal carotid artery occlusion (ICAO) is defined as “untouchable” by all specialists; no treatment is indicated because intervention risks (carotid endarterectomy (CEA) or endovascular treatment) are usually much more than benefits. We report the case of a patient admitted to our hospital with an atherothrombotic ischemic stroke due to symptomatic acute ICAO, who developed a recurrent stroke with hemispheric hypoperfusion and was treated in the emergency department with ICAO revascularization after 60 days of occlusion finding. Case Description D.G., a 62-year-old man, came to our attention for a transient episode of left weakness and hypoesthesia. The electrocardiogram revealed a new diagnosis of atrial fibrillation. CT angiography showed right ICAO; computed tomography and magnetic resonance imaging studies with perfusion imaging revealed a severe hemispheric hypoperfusion. Full anticoagulation therapy was started, and antihypertensive therapy was reduced to help collateral circulation. Some weeks later, the patient was readmitted to the stroke unit for 2 episodes of left-hand weakness. Cerebral angiography confirmed right ICAO from the proximal tract to the siphon. After some days, the patient suffered a femoral hemorrhagic lesion, with active bleeding, and was treated with surgical intervention. On the following day, the patient presented with left hemiplegia with hemianesthesia (National Institutes of Health Stroke Scale score = 14). The patient was treated in the emergency department with a complex endovascular treatment with complete recanalization of ICAO by positioning 3 stents through the intravenous infusion of abciximab. After intensive rehabilitation, at the 3- and 6-month follow-up evaluations, the patient regained autonomy. Conclusion In literature, treatment of chronic ICAO is not indicated. Endovascular recanalization may be beneficial to patients with chronic cerebral hypoperfusion due to ICAO, when all conservative medical therapies have failed.

2015 - A one-year prospective study of refractory status epilepticus in Modena, Italy [Articolo su rivista]
Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus".

2015 - A topographical organization for action representation in the human brain [Articolo su rivista]
Handjaras, G.; Bernardi, G.; Benuzzi, F.; Nichelli, P. F.; Pietrini, P.; Ricciardi, E.
abstract

How the human brain represents distinct motor features into a unique finalized action still remains undefined. Previous models proposed the distinct features of a motor act to be hierarchically organized in separated, but functionally interconnected, cortical areas. Here, we hypothesized that distinct patterns across a wide expanse of cortex may actually subserve a topographically organized coding of different categories of actions that represents, at a higher cognitive level and independently from the distinct motor features, the action and its final aim as a whole. Using functional magnetic resonance imaging and pattern classification approaches on the neural responses of 14 right-handed individuals passively watching short movies of hand-performed tool-mediated, transitive, and meaningful intransitive actions, we were able to discriminate with a high accuracy and characterize the category-specific response patterns. Actions are distinctively coded in distributed and overlapping neural responses within an action-selective network, comprising frontal, parietal, lateral occipital and ventrotemporal regions. This functional organization, that we named action topography, subserves a higher-level and more abstract representation of finalized actions and has the capacity to provide unique representations for multiple categories of actions.

2015 - Absence of change in the gray matter volume of patients with ulcerative colitis in remission: a voxel based morphometry study [Articolo su rivista]
Agostini, Alessandro; Campieri, Massimo; Bertani, Angela; Scarcelli, Antonella; Ballotta, Daniela; Calabrese, Carlo; Rizzello, Fernando; Gionchetti, Paolo; Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

Background: Recent neuroimaging studies have investigated the brain involvement in patients with Crohn's disease (CD) and Ulcerative Colitis (UC). Functional studies found abnormalities in cognitive and emotional functions in CD and UC, while a voxel based morphometry (VBM) study found morphological changes in CD. We conducted a VBM study to compare the gray matter (GM) volume of UC patients and controls. Methods: Eighteen UC patients in remission and eighteen healthy controls underwent structural MRI. VBM is a fully automated technique allowing identification of regional differences in the amount of GM, which enables an objective analysis of the whole brain. VBM was used for comparisons between patients and controls. Results: UC patients were all in remission and had a mild clinical course. There were no differences between patients and controls in GM volume. Conclusion: The brain morphology of patients with UC in remission is similar to controls. The lack of GM abnormalities in UC patients might reflect the mild clinical course of the inflammatory bowel disorder. Further research involving patients with different degrees of disease severity or during flares could shed more light on potential brain structural changes in UC.

2015 - An EEG-fMRI Study on the Termination of Generalized Spike-And-Wave Discharges in Absence Epilepsy [Articolo su rivista]
Benuzzi, Francesca; Ballotta, Daniela; Mirandola, Laura; Ruggieri, Andrea; Vaudano, Anna Elisabetta; Zucchelli, Micaela Maria; Ferrari, Elisabetta; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

INTRODUCTION: Different studies have investigated by means of EEG-fMRI coregistration the brain networks related to generalized spike-and-wave discharges (GSWD) in patients with idiopathic generalized epilepsy (IGE). These studies revealed a widespread GSWD-related neural network that involves the thalamus and regions of the default mode network. In this study we investigated which brain regions are critically involved in the termination of absence seizures (AS) in a group of IGE patients. METHODS: Eighteen patients (6 male; mean age 25 years) with AS were included in the EEG-fMRI study. Functional data were acquired at 3T with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at single-subject and at group level with a second level random effect analysis. RESULTS: A mean of 17 events for patient was recorded (mean duration of 4.2 sec). Group-level analysis related to GSWD onset respect to rest confirmed previous findings revealing thalamic activation and a precuneus/posterior cingulate deactivation. At GSWD termination we observed a decrease in BOLD signal over the bilateral dorsolateral frontal cortex respect to the baseline (and respect to GSWD onset). The contrast GSWD offset versus onset showed a BOLD signal increase over the precuneus-posterior cingulate region bilaterally. Parametric correlations between electro-clinical variables and BOLD signal at GSWD offset did not reveal significant effects. CONCLUSION: The role of the decreased neural activity of lateral prefrontal cortex at GSWD termination deserve future investigations to ascertain if it has a role in promoting the discharge offset, as well as in the determination of the cognitive deficits often present in patients with AS. The increased BOLD signal at precuneal/posterior cingulate cortex might reflect the recovery of neural activity in regions that are "suspended" during spike and waves activity, as previously hypothesized.

2015 - Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis [Articolo su rivista]
Ferraro, Diana; Galli, Veronica; Vitetta, Francesca; Simone, Anna Maria; Bedin, Roberta; Del Giovane, Cinzia; Morselli, Franca; Filippini, Maria Maddalena; Nichelli, Paolo Frigio; Sola, Patrizia
abstract

Cerebrospinal fluid (CSF) CXCL13 was shown to correlate with markers of intrathecal inflammation and CSF oligoclonal IgM bands (IgMOB) have been associated with a more severe Multiple Sclerosis (MS) course.We correlated CSF CXCL13 levels with clinical, MRI and CSF parameters, including CSF IgMOB, in 110 Clinically Isolated Syndrome (CIS) patients.CSF CXCL13 levels correlated with CSF cell count, total protein, IgG Index and with the presence of CSF IgGOB and IgMOB.CSF CXCL13 levels ≥. 15.4. pg/ml showed a good positive predictive value and specificity for a MS diagnosis and for a clinical relapse within one year from onset.

2015 - Cerebrospinal fluid tau proteins in status epilepticus [Articolo su rivista]
Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo Frigio; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa
abstract

Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR=32.5, p=0.004) and chronic epilepsy (OR=12; p=0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus".

2015 - Corrigendum to Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III [Mol. Oncol. 8 (2) (2014) 417-30] [Articolo su rivista]
Visani, M.; de Biase, D.; Marucci, G.; Cerasoli, S.; Nigrisoli, E.; Bacchi Reggiani, M. L.; Albani, F.; Baruzzi, A.; Pession, A.; Agati, R.; Ambrosetto, G.; Bacci, A.; Baldin, E.; Baldrati, A.; Barbieri, E.; Bartolini, S.; Bellavista, E.; Bisulli, F.; Bonora, E.; Bunkheila, F.; Carelli, V.; Crisci, M.; Dall'Occa, P.; Ferro, S.; Franceschi, C.; Frezza, G.; Grasso, V.; Leonardi, M.; Morandi, L.; Mostacci, B.; Palandri, G.; Pasini, E.; Pastore Trossello, M.; Poggi, R.; Riguzzi, P.; Rinaldi, R.; Rizzi, S.; Romeo, G.; Spagnolli, F.; Tinuper, P.; Trocino, C.; Frattarelli, M.; Giovannini, A.; Iorio, P.; Pasquini, U.; Galletti, G.; Guidi, C.; Neri, W.; Patuelli, A.; Strumia, S.; Dall'Agata, M.; Faedi, M.; Gentili, G.; Zumaglini, F.; Casmiro, M.; Gamboni, A.; Rasi, F.; Cruciani, G.; Cenni, P.; Dazzi, C.; Guidi, A. R.; Amadori, A.; Pasini, G.; Pasquinelli, M.; Pasquini, E.; Polselli, A.; Ravasio, A.; Viti, B.; Sintini, M.; Ariatti, A.; Bertolini, F.; Bigliardi, G.; Carpeggiani, P.; Cavalleri, F.; Meletti, S.; Nichelli, P.; Pettorelli, E.; Pinna, G.; Zunarelli, E.; Artioli, F.; Bernardini, I.; Costa, M.; Greco, G.; Guerzoni, R.; Stucchi, C.; Ragazzi, M.; Iaccarino, C.; Rizzi, R.; Zuccoli, G.; Api, P.; Cartei, F.; Fallica, E.; Granieri, E.; Latini, F.; Lelli, G.; Monetti, C.; Saletti, A.; Schivalocchi, R.; Seraceni, S.; Tola, M. R.; Urbini, B.; Giorgi, C.; Montanari, E.; Cerasti, D.; Crafa, P.; Dascola, I.; Florindo, I.; Giombelli, E.; Mazza, S.; Ramponi, V.; Servadei, F.; Silini, E. M.; Torelli, P.; Immovilli, P.; Morelli, N.; Vanzo, C.; Nobile, C.
abstract

2015 - MRI correlates of Parkinson's disease progression: A voxel based morphometry study [Articolo su rivista]
Fioravanti, V.; Benuzzi, F.; Codeluppi, L.; Contardi, S.; Cavallieri, F.; Nichelli, P.; Valzania, F.
abstract

We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients.

2015 - Mapping (and modeling) physiological movements during EEG-fMRI recordings: the added value of the video acquired simultaneously [Articolo su rivista]
Ruggieri, Andrea; Vaudano, Anna Elisabetta; Benuzzi, Francesca; Serafini, Marco; Gessaroli, Giuliana; Farinelli, Valentina; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Background: During resting-state EEG-fMRI studies in epilepsy, patients' spontaneous head-face movements occur frequently. We tested the usefulness of synchronous video recording to identify and model the fMRI changes associated with non-epileptic movements to improve sensitivity and specificity of fMRI maps related to interictal epileptiform discharges (IED). New methods: Categorization of different facial/cranial movements during EEG-fMRI was obtained for 38 patients [with benign epilepsy with centro-temporal spikes (BECTS, n = 16); with idiopathic generalized epilepsy (IGE, n = 17); focal symptomatic/cryptogenic epilepsy (n = 5)]. We compared at single subject-and at group-level the IED-related fMRI maps obtained with and without additional regressors related to spontaneous movements. As secondary aim, we considered facial movements as events of interest to test the usefulness of video information to obtain fMRI maps of the following face movements: swallowing, mouth-tongue movements, and blinking. Results: Video information substantially improved the identification and classification of the artifacts with respect to the EEG observation alone (mean gain of 28 events per exam). Comparison with existing method: Inclusion of physiological activities as additional regressors in the GLM model demonstrated an increased Z-score and number of voxels of the global maxima and/or new BOLD clusters in around three quarters of the patients. Video-related fMRI maps for swallowing, mouth-tongue movements, and blinking were comparable to the ones obtained in previous task-based fMRI studies. Conclusions: Video acquisition during EEG-fMRI is a useful source of information. Modeling physiological movements in EEG-fMRI studies for epilepsy will lead to more informative IED-related fMRI maps in different epileptic conditions.

2015 - Methylprednisolone-induced toxic hepatitis after intravenous pulsed therapy for multiple sclerosis relapses [Articolo su rivista]
Ferraro, Diana; Mirante, Vincenzo G.; Losi, Luisa; Villa, Erica; Simone, ANNA MARIA; Vitetta, Francesca; Federzoni, Lucia; Nichelli, Paolo Frigio; Sola, Patrizia
abstract

High-dose, intravenous methylprednisolone (MP) is the only recommended first-line treatment for multiple sclerosis relapses. However, there are increasing reports on liver toxicity induced by this treatment regimen. We report of 4 multiple sclerosis patients with no history of viral/metabolic liver disorders or alcohol/hepatotoxic drug intake, who developed hypertransaminasaemia following intravenous MP. In 2 of the patients, liver biopsy showed periportal fibrosis, piecemeal necrosis, and inflammatory cell infiltrates. A rechallenge test confirmed a causal association in 1 case. MP-induced liver toxicity may be more frequent than commonly thought and it is important to report this adverse reaction, which is potentially lethal, and to raise awareness on the potential hepatotoxicity of corticosteroid pulses.

2015 - Neural correlates in intertemporal choice of gains and losses [Articolo su rivista]
Faralla, Valeria; Benuzzi, Francesca; Lui, Fausta; Baraldi, Patrizia; Dimitri, Nicola; Nichelli, Paolo Frigio
abstract

Intertemporal choices are decisions involving trade-offs among payoffs available at different points in time. We used event-related functional MRI to investigate the neural mechanisms underlying intertemporal preference for symmetric monetary gains and losses, by asking subjects to choose between 2 gains or 2 losses available at different time delays. We also explored how neural networks are modulated by time delay and by the monetary difference between the 2 alternatives. Our findings indicate that a common widespread neural network involving occipital, parietal, and prefrontal cortex is activated in the processing of both gains and losses, thus suggesting that the same brain structures support different economically relevant behaviors, independently of the sign of the outcome. Two different neural circuits were found to be engaged in processing immediate and delayed monetary outcomes. Regions of the emotional system, namely, posterior cingulate and medial prefrontal cortex, were recruited when an immediate option (gain/loss) was chosen. In contrast, occipital and parietal cortex, in association with lateral and dorsolateral prefrontal cortex, were engaged in delayed choices.

2015 - Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study [Articolo su rivista]
Tondelli, Manuela; Bedin, Roberta; Chiari, Annalisa; Molinari, Maria Angela; Bonifacio, GUENDALINA BEATRICE; Lelli, Nicoletta; Trenti, Tommaso; Nichelli, Paolo Frigio
abstract

Abstract Background: Cerebrospinal fluid (CSF) levels assessment of Aβ1-42 and Tau proteins may be accurate diagnostic biomarkers for the differentiation of preclinical Alzheimer's disease (AD) from age-associated memory impairment, depression and other forms of dementia in patients with mild cognitive impairment (MCI). The aim of our study was to explore the utility of CSF biomarkers in combination with common cognitive markers as predictors for the risk of AD development, and other forms of dementia, and the time to conversion in community patients with MCI. Methods: A group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tau181, Aβ1-42. We investigated baseline CSF and neuropsychological biomarker patterns according to groups stratified with later diagnoses of AD conversion (MCI-AD), other dementia (MCI-NAD) conversion, or clinical stability (sMCI). Results: Baseline Aβ1-42 CSF levels were significantly lower in MCI-AD patients compared to both sMCI and MCI-NAD. Additionally, p-tau181 was higher in the MCI-AD group compared to sMCI. The MCI-AD subgroup analysis confirmed the role of Aβ1-42 in its predictive role of time to conversion: rapid converters had lower Aβ1-42 levels compared to slow converters. Logistic regression and survival analysis further supported the key predictive role of baseline Aβ1-42 for incipient AD and dementia-free survival. Conclusions: Our results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting.

2015 - The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy [Articolo su rivista]
Meletti, Stefano; Vaudano, Anna Elisabetta; Pizza, Fabio; Ruggieri, Andrea; Vandi, Stefano; Teggi, Alberto; Franceschini, Christian; Benuzzi, Francesca; Nichelli, Paolo Frigio; Plazzi, Giuseppe
abstract

The brain suprapontine mechanisms associated with human cataplexy have not been clarified. Animal data suggest that the amygdala and the ventromedial prefrontal cortex are key regions in promoting emotion-induced cataplectic attacks. Twenty-one drug-naive children/adolescent (13 males, mean age 11 years) with recent onset of narcolepsy type 1 (NT1) were studied with fMRI while viewing funny videos using a "naturalistic" paradigm. fMRI data were acquired synchronously with EEG, mylohyoid muscle activity, and the video of the patient's face. Whole-brain hemodynamic correlates of (1) a sign of fun and amusement (laughter) and of (2) cataplexy were analyzed and compared. Correlations analyses between these contrasts and disease-related variables and behavioral findings were performed.

2014 - Epilepsy-related brain networks in ring chromosome 20 syndrome: An EEG-fMRI study [Articolo su rivista]
Vaudano, ANNA ELISABETTA; Ruggieri, Andrea; Aglaia, Vignoli; Avanzini, Pietro; Benuzzi, Francesca; Giuliana, Gessaroli; Nichelli, Paolo Frigio; Francesca, Darra; Gaetano, Cantalupo; Massimo, Mastrangelo; Bernardo Dalla Bernardina, ; Maria Paola Canevini, ; Meletti, Stefano
abstract

To identify the brain networks that are involved in the different electroencephalography (EEG) abnormalities in patients with ring chromosome 20 [r(20)] syndrome. We hypothesize the existence of both distinctive and common brain circuits for the paroxysmal high voltage sharp waves (hSWs), the seizures, and the slow-wave 3-7 Hz rhythm that characterize this condition. METHODS: Thirteen patients with [r(20)] syndrome were studied by means of EEG simultaneously recorded with functional magnetic resonance imaging (EEG-fMRI). EEG traces were reviewed in order to detect the pathologic interictal (hSWs) and ictal activities; the 3-7 Hz theta-delta power was derived using a fast Fourier transform. A group-level analysis was performed for each type of EEG abnormality separately using a fixed-effect model and a conjunction analysis. Finally, a second-level random-effect model was applied considering together the different EEG abnormalities, without distinction between hSW, seizures, or theta-delta rhythms. RESULTS: Subcontinuous theta-delta rhythm was recorded in seven patients, seizures in two, and hSWs in three patients. The main results are the following: (1) the slow-wave rhythm was related to blood oxygen level-dependent (BOLD) increases in the premotor, sensory-motor, and temporoparietal cortex, and to BOLD decrements involving the default mode (DMN) and the dorsal attention networks (DANs); (2) the ictal-related BOLD changes showed an early involvement of the prefrontal lobe; (3) increases in BOLD signal over the basal ganglia, either for interictal and ictal activities, were observed; (4) a common pattern of positive BOLD changes in the bilateral perisylvian regions was found across the different EEG abnormalities. SIGNIFICANCE: The BOLD increment in the perisylvian network and the decrease of the DMN and DAN could be the expression of the [r(20)] syndrome-related cognitive and behavioral deficits. The observed BOLD patterns are similar to the ones detected in other epileptic encephalopathies, suggesting that different epileptic disorders characterized by neurobehavioral regression are associated with dysfunction in similar brain networks. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

2014 - Low frequency mu-like activity characterizes cortical rhythms in epilepsy due to ring chromosome 20. [Articolo su rivista]
P., Avanzini; A. E., Vaudano; A., Vignoli; Ruggieri, Andrea; Benuzzi, Francesca; F., Darra; M., Mastrangelo; B. D., Bernardina; Nichelli, Paolo Frigio; M. P., Canevini; Meletti, Stefano
abstract

Objectives: To evaluate the spectral and spatial features of the cortical rhythms in patients affected by ring chromosome 20 - [r(20)]-syndrome. Methods: Twelve patients with [r(20)] syndrome were studied. As controls we enrolled 12 patients with idiopathic generalized epilepsy (IGE) and 12 healthy volunteers (HV). Blind source separation, spectral analyses and source reconstruction were applied in all cases in order to identify reliable spatio-temporal patterns of cortical activity. Results: A theta-delta EEG rhythm was identified in [r(20)] patients, with spectral peak ranging between 3 and 7 Hz and whose generators mapped over the sensory-motor cortices. A second peak laying at a frequency about double with respect to the first one was present in 6 cases. Analogue methodological approach in HV and IGE groups failed to show similar findings. Conclusions: EEG of [r(20)] patients reveals the existence of a highly reproducible EEG pattern arising from the sensory-motor system. Significance: The recognition of this peculiar EEG pattern could help the diagnostic work-up. Additionally, our findings supports the existence of a parallelism between this EEG trait and the physiological "mu" rhythm which is generate by the sensory-motor system. Such link suggests a sensory-motor system dysfunction in [r(20)] patients. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

2014 - Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center? [Articolo su rivista]
Brandes, Alba A; Franceschi, Enrico; Ermani, Mario; Tosoni, Alicia; Albani, Fiorenzo; Depenni, Roberta; Faedi, Marina; Pisanello, Anna; Crisi, Girolamo; Urbini, Benedetta; Dazzi, Claudio; Cavanna, Luigi; Mucciarini, Claudia; Pasini, Giuseppe; Bartolini, Stefania; Marucci, Gianluca; Morandi, Luca; Zunarelli, Elena; Cerasoli, Serenella; Gardini, Giorgio; Lanza, Giovanni; Silini, Enrico Maria; Cavuto, Silvio; Baruzzi, Agostino; Baruzzi, A; Albani, F; Calbucci, F; D'Alessandro, R; Michelucci, R; Brandes, A; Eusebi, V; Ceruti, S; Fainardi, E; Tamarozzi, R; Emiliani, E; Cavallo, M; Franceschi, E; Tosoni, A; Cavallo, M; Fiorica, F; Valentini, A; Depenni, R; Mucciarini, C; Crisi, G; Sasso, E; Biasini, C; Cavanna, L; Guidetti, D; Marcello, N; Pisanello, A; Cremonini, A. M; Guiducci, G; de Pasqua, S; Testoni, S; Agati, R; Ambrosetto, G; Bacci, A; Baldin, E; Baldrati, A; Barbieri, E; Bartolini, S; Bellavista, E; Bisulli, F; Bonora, E; Bunkheila, F; Carelli, V; Crisci, M; Dall'Occa, P; de Biase, D; Ferro, S; Franceschi, C; Frezza, G; Grasso, V; Leonardi, M; Marucci, G; Mazzocchi, V; Morandi, L; Mostacci, B; Palandri, G; Pasini, E; Pastore Trossello, M; Pession, A; Ragazzi, M; Riguzzi, P; Rinaldi, R; Rizzi, S; Romeo, G; Spagnolli, F; Tinuper, P; Trocino, C; Cerasoli, S; Dall'Agata, M; Faedi, M; Frattarelli, M; Gentili, G; Giovannini, A; Iorio, P; Pasquini, U; Galletti, G; Guidi, C; Neri, W; Patuelli, A; Strumia, S; Casmiro, M; Gamboni, A; Rasi, F; Cruciani, G; Cenni, P; Dazzi, C; Guidi, Ar; Zumaglini, F; Amadori, A; Pasini, G; Pasquinelli, M; Pasquini, E; Polselli, A; Ravasio, A; Viti, B; Sintini, M; Ariatti, A; Bertolini, F; Bigliardi, G; Carpeggiani, P; Cavalleri, F; Meletti, Stefano; Nichelli, Paolo Frigio; Pettorelli, E; Pinna, G; Zunarelli, E; Artioli, F; Bernardini, I; Costa, M; Greco, G; Guerzoni, R; Stucchi, C; Iaccarino, C; Rizzi, R; Zuccoli, G; Api, P; Cartei, F; Fallica, E; Granieri, E; Latini, F; Lelli, G; Monetti, C; Ramponi, V; Saletti, A; Schivalocchi, R; Seraceni, S; Tola, M. R; Urbini, B; Giorgi, C; Montanari, E; Cerasti, D; Crafa, P; Dascola, I; Florindo, I; Mazza, S; Servadei, F; Silini, Em; Torelli, P; Immovilli, P; Morelli, N; Vanzo, C.
abstract

BACKGROUND:As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

2014 - Pearls & Oy-sters: rapidly progressive dementia: prions or immunomediated? [Articolo su rivista]
Cavallieri, Francesco; Mandrioli, Jessica; Tondelli, Manuela; Vitetta, Francesca; Stipa, Carlotta; Vallone, Stefano; Georgoulopoulou, Eleni; Barbi, Filippo; Liguori, Rocco; Parchi, Piero; Nichelli, Paolo Frigio
abstract

The paper presentes a case report of a patient with rapidly progressive dementia. The discussion is focused on the differential diagnosis between Voltage-gated potassium channel antibody–associated encephalitis and sporadic Creutzfeldt-Jakob disease.

2014 - Progressive bilateral medial medullary infarction [Articolo su rivista]
Codeluppi, Luca; Giovannini, Giada; Carpeggiani, Paolo; Nichelli, Paolo Frigio; Zini, Andrea
abstract

This is the report of a rare case of blateral medial medullary infarction

2014 - Recovery from Emotion Recognition Impairment after Temporal Lobectomy [Articolo su rivista]
Benuzzi, Francesca; Zamboni, Giovanna; Meletti, Stefano; Serafini, Marco; Lui, Fausta; Baraldi, Patrizia; Duzzi, Davide; Rubboli, Guido; Albertotassinari, Carlo; Nichelli, Paolo Frigio
abstract

Mesial temporal lobe epilepsy (MTLE) can be associated with emotion recognition impairment that can be particularly severe in patients with early onset seizures (1–3). Whereas, there is growing evidence that memory and language can improve in seizure-free patients after anterior temporal lobectomy (ATL) (4), the effects of surgery on emotional processing are still unknown. We used functional magnetic resonance imaging (fMRI) to investigate short-term reorganization of networks engaged in facial emotion recognition in MTLE patients. Behavioral and fMRI data were collected from six patients before and after ATL. During the fMRI scan, patientswere asked to make a gender decision on fearful and neutral faces. Behavioral data demonstrated that two patients with early onset right MTLE were impaired in fear recognition while fMRI results showed they lacked specific activations for fearful faces. Post-ATL behavioral data showed improved emotion recognition ability, while fMRI demonstrated the recruitment of a functional network for fearful face processing. Our results suggest that ATL elicited brain plasticity mechanisms allowing behavioral and fMRI improvement in emotion recognition.

2014 - Severe anemia in a patient with multiple sclerosis treated with natalizumab [Articolo su rivista]
Simone, ANNA MARIA; Ferraro, Diana; Vitetta, Francesca; Marasca, Roberto; Bonacorsi, Goretta; Pinelli, Giovanni; Federzoni, Lucia; Nichelli, Paolo Frigio; Sola, Patrizia
abstract

The paper is a case report of a 51-year-old woman with a 16-year history of relapsing-remitting multiple sclerosis, who developed a severe anemia following a treatment with natalizumab

2014 - The visual system in eyelid myoclonia with absences [Articolo su rivista]
Vaudano, ANNA ELISABETTA; Ruggieri, Andrea; Tondelli, Manuela; Avanzini, Pietro; Benuzzi, Francesca; Giuliana, Gessaroli; Gaetano, Cantalupo; Massimo, Mastrangelo; Aglaia, Vignoli; Carlo Di Bonaventura, ; Maria Paola Canevini, ; Bernardo Dalla Bernardina, ; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

OBJECTIVE: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]). METHODS: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and between-groups comparisons were performed for fMRI and VBM data as appropriate. RESULTS: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE. INTERPRETATION: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes.

2013 - Causality within the Epileptic Network: An EEG-fMRI Study Validated by Intracranial EEG [Articolo su rivista]
Anna Elisabetta, Vaudano; Avanzini, Pietro; Laura, Tassi; Ruggieri, Andrea; Gaetano, Cantalupo; Benuzzi, Francesca; Nichelli, Paolo Frigio; Louis, Lemieux; Meletti, Stefano
abstract

Accurate localization of the Seizure Onset Zone (SOZ) is crucial in patients with drug-resistance focal epilepsy. EEG with fMRI recording (EEG-fMRI) has been proposed as a complementary non-invasive tool, which can give useful additional information in the pre-surgical work-up. However, fMRI maps related to interictal epileptiform activities (IED) often show multiple regions of signal change, or "networks," rather than highly focal ones. Effective connectivity approaches like Dynamic Causal Modeling (DCM) applied to fMRI data potentially offers a framework to address which brain regions drives the generation of seizures and IED within an epileptic network. Here, we present a first attempt to validate DCM on EEG-fMRI data in one patient affected by frontal lobe epilepsy. Pre-surgical EEG-fMRI demonstrated two distinct clusters of blood oxygenation level dependent (BOLD) signal increases linked to IED, one located in the left frontal pole and the other in the ipsilateral dorso-lateral frontal cortex. DCM of the IED-related BOLD signal favored a model corresponding to the left dorso-lateral frontal cortex as driver of changes in the fronto-polar region. The validity of DCM was supported by: (a) the results of two different non-invasive analysis obtained on the same dataset: EEG source imaging (ESI), and "psycho-physiological interaction" analysis; (b) the failure of a first surgical intervention limited to the fronto-polar region; (c) the results of the intracranial EEG monitoring performed after the first surgical intervention confirming a SOZ located over the dorso-lateral frontal cortex. These results add evidence that EEG-fMRI together with advanced methods of BOLD signal analysis is a promising tool that can give relevant information within the epilepsy surgery diagnostic work-up.

2013 - Centrotemporal spikes during NREM sleep: The promoting action of thalamus revealed by simultaneous EEG and fMRI coregistration [Articolo su rivista]
Mirandola, Laura; Gaetano, Cantalupo; Vaudano, ANNA ELISABETTA; Pietro, Avanzini; Ruggieri, Andrea; Francesco, Pisani; Giuseppe, Cossu; Carlo Alberto, Tassinari; Nichelli, Paolo Frigio; Benuzzi, Francesca; Meletti, Stefano
abstract

Benign childhood epilepsy with centrotemporal spikes (BECTS) has been investigated through EEG–fMRI with the aim of localizing the generators of the epileptic activity, revealing, in most cases, the activation of the sensory–motor cortex ipsilateral to the centrotemporal spikes (CTS). In this case report, we investigated the brain circuits hemodynamically involved by CTS recorded during wakefulness and sleep in one boy with CTS and a language disorder but without epilepsy. For this purpose, the patient underwent EEG–fMRI coregistration. During the “awake session”, fMRI analysis of right-sided CTS showed increments of BOLD signal in the bilateral sensory–motor cortex. During the “sleep session”, BOLD increments related to right-sided CTS were observed in a widespread bilateral cortical–subcortical network involving the thalamus, basal ganglia, sensory–motor cortex, perisylvian cortex, and cerebellum. In this patient, who fulfilled neither the diagnostic criteria for BECTS nor that for electrical status epilepticus in sleep (ESES), the transition from wakefulness to sleep was related to the involvement of a widespread cortical–subcortical network related to CTS. In particular, the involvement of a thalamic–perisylvian neural network similar to the one previously observed in patients with ESES suggests a common sleep-related network dysfunction even in cases with milder phenotypes without seizures. This finding, if confirmed in a larger cohort of patients, could have relevant therapeutic implication.

2013 - Cerebrospinal fluid oligoclonal IgM bands predict early conversion to clinically definite multiple sclerosis in patients with Clinically Isolated Syndrome. [Articolo su rivista]
Ferraro, Diana; Simone, ANNA MARIA; Bedin, Roberta; Galli, Veronica; Vitetta, F; Federzoni, L; D'Amico, Roberto; Merelli, E; Nichelli, Paolo Frigio; Sola, P.
abstract

We reviewed the records of 391 patients who had presented with a Clinically Isolated Syndrome and selected 205 who had performed a baseline spinal tap and MRI scan. We studied cerebrospinal fluid (CSF) and serum IgM oligoclonal bands (IgMOB) using agarose gel isoelectric focusing and analyzed the impact of baseline clinical, MRI and CSF variables on the risk of conversion to clinically definite multiple sclerosis, i.e. on the risk of a clinical relapse. At survival analysis, a lower age at onset, an onset with optic neuritis and the presence of CSF-restricted IgMOB increased the risk of a relapse. Only the presence of CSF-restricted IgMOB predicted a relapse within one year.

2013 - Definition of miRNAs expression profile in glioblastoma samples: the relevance of non-neoplastic brain reference. [Articolo su rivista]
M., Visani; D. d., Biase; G., Marucci; C., Taccioli; A., Baruzzi; A., Pession; A., Ariatti; B., Bertolini; G., Bigliardi; P., Carpeggiani; F., Cavalleri; Meletti, Stefano; Nichelli, Paolo Frigio; G., Pinna; E., Zunarelli; A., Pession; PERNO study, Group
abstract

Glioblastoma is the most aggressive brain tumor that may occur in adults. Regardless of the huge improvements in surgery and molecular therapy, the outcome of neoplasia remains poor. MicroRNAs are small molecules involved in several cellular processes, and their expression is altered in the vast majority of tumors. Several studies reported the expression of different miRNAs in glioblastoma, but one of the most critical point in understanding glioblastoma miRNAs profile is the comparison of these studies. In this paper, we focused our attention on the non-neoplastic references used for determining miRNAs expression. The aim of this study was to investigate if using three different non-neoplastic brain references (normal adjacent the tumor, commercial total RNA, and epileptic specimens) could provide discrepant results. The analysis of 19 miRNAs was performed using Real-Time PCR, starting from the set of samples described above and the expression values compared. Moreover, the three different normal RNAs were used to determine the miRNAs profile in 30 glioblastomas. The data showed that different non-neoplastic controls could lead to different results and emphasize the importance of comparing miRNAs profiles obtained using the same experimental condition.

2013 - Frequent early multiple sclerosis relapses during treatment with fingolimod: a paradoxical effect? [Articolo su rivista]
Ferraro, Diana; Federzoni, Lucia; Vitetta, F; Simone, ANNA MARIA; Cossarizza, Andrea; Nichelli, Paolo Frigio; Sola, P.
abstract

This is the case report of a multiple sclerosi patient who presented frequent relapses early after beginning a treatment with fingolimod

2013 - Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn's disease versus healthy controls [Articolo su rivista]
A., Agostini; N., Filippini; Benuzzi, Francesca; A., Bertani; A., Scarcelli; C., Leoni; V., Farinelli; D., Riso; R., Tambasco; C., Calabrese; F., Rizzello; P:, Gionchetti; M., Ercolani; Nichelli, Paolo Frigio; M., Campieri
abstract

In patients with Crohn's disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD

2013 - Gains and losses in intertemporal preferences: a behavioural study [Capitolo/Saggio]
V., Faralla; Benuzzi, Francesca; Nichelli, Paolo Frigio; N., Dimitri
abstract

The aim of this study was to investigate individual behavior in choosing symmetric monetary gains and losses under certainty. As in previous research, results showed that gains and losses are not equal and seem to be drawn by different internal principles of choice. Subjects preferred to lose sooner in time against average or high losses. Furthermore, considering the proportional difference between short and long-term alternatives of choice, the percentage of responses for early outcomes was increasing for losses and decreasing for gains.

2013 - Generalized spike-and-wave discharges offset is related to precuneal-posterior cingulate activity. [Poster]
Benuzzi, Francesca; Zuccheli, M.; Ferrari, E.; Vaudano, A. E.; Ruggieri, Andrea; Mirandola, Laura; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Introduction: Recent EEG-fMRI studies revealed that a widespread neural network subserves the generation of ictal and interictal activity in patients with generalized epilepsy (1-4). Different studies investigated the hemodynamic changes related to the onset and duration of generalized spike-and-wave discharges (GSWD) in human epilepsy. Conversely, the BOLD signal changes related to GSWD termination has not been addressed to date. Few studies have focused the mechanisms that promote seizures stop at molecular and cellular level (6). In particular, a recent single neuron recording study in human focal epilepsy (7) revealed that neuronal firing patterns change homogeneously at seizure offset suggesting that seizure termination is marked by an abrupt homogeneous change in neuronal firing. These data support a mechanism that acts at the neural network level. The present EEG-fMRI study aimed at evaluating the neural correlates of seizure termination studying the BOLD variations at GSWD offset in a large sample of patients with Idiopathic generalized epilepsy (IGE). Materials and methods: eighteen patients (6 male; mean age 25 yrs.) with IGE were included. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system. Functional data were acquired with a 3T Philips Intera System (TR=3000 ms) from 30 axial contiguous 4 mm slices (64 x 64 matrix) over two-three 10-min sessions per patient with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at a second level random effect analysis. Results: a mean of 17 events for each patient was recorded (mean duration= 4 s). Second-level random effect analysis related to onset and GSWD length confirmed previous findings (5) revealing a thalamus activation and a parietal and precuneus-posterior cingulate deactivation. GSWD onset respect to the offset showed BOLD increases in the prefrontal regions (inferior and middle frontal gyrus) mostly on the left side and in the bilateral primary visual cortex. Conversely, GSWD offset respect to the onset revealed significant hemodynamic changes over the precuneus-posterior cingulate region (Fig. 1). Conclusions: fMRI results showed that the neural network at GSWD termination involved precuneus-posterior cingulate region. These findings confirm an important role of this brain region in GSWD pathophysiology. Particularly, precuneal/posterior cingulate neuronal activity might participate actively to the GSWD termination or it might reflect the recovery of the awareness impaired during the pathological activity. BIBLIOGRAFY 1) Gotman J, Grova C, Bagshaw A, Kobayashi E, Aghakhani Y, Dubeau F. (2005) Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci USA, vol. 102, pp. 15236–15240. 2) Moeller F, Siebner HR, Wolff S, Muhle H, Boor R, Granert O, Jansen O, Stephani U, Siniatchkin M. (2008) Changes in activity of striato-thalamo- cortical network precede generalized spike wave discharges. Neuroimage vol. 39, pp. 1839–1849. 3) Vaudano AE, Laufs H, Kiebel SJ, Carmichael DW, Hamandi K, Guye M, Thornton R, Rodionov R, Friston KJ, Duncan JS, Lemieux L. (2009) Causal hierarchy within the thalamo-cortical network in spike and wave discharges. PLoS ONE vol. 4:e6475. 4) Carney PW, Masterton RA, Harvey AS, Scheffer IE, Berkovic SF, Jackson GD. (2010) The core network in absence epilepsy. Differences in cortical and thalamic BOLD response. Neurology vol. 75, pp. 904–911. 5) Benuzzi F, Mirandola L, Pugnaghi M, Farinelli V, Tassinari CA, Capovilla G, Cantalupo G, Beccaria F, Nichelli P, Meletti S (2012). Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies. Epilepsia, vol. 53(4

2013 - Hypoxia markers are expressed in interneurons exposed to recurrent seizures. [Articolo su rivista]
Gualtieri, Fabio; C., Marinelli; Longo, Daniela; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Meletti, Stefano; Biagini, Giuseppe
abstract

An early but transient decrease in oxygen availability occurs during experimentally induced seizures. Using pimonidazole, which probes hypoxic insults, we found that by increasing the duration of pilocarpine-induced status epilepticus (SE) from 30 min to 120 min, counts of pimonidazole-immunoreactive neurons also increased (P < 0.01, 120 vs 60 and 30 min). All the animals exposed to SE were immunopositive to pimonidazole, but a different scenario emerged during epileptogenesis when a decrease in pimonidazole immunostained cells occurred from 7 to 14 days, so that only 1 out of 4 rats presented with pimonidazole-immunopositive cells. Pimonidazole-immunoreactive cells robustly reappeared at 21 days post-SE induction when all animals (7 out of 7) had developed spontaneous recurrent seizures. Specific neuronal markers revealed that immunopositivity to pimonidazole was present in cells identified by neuropeptide Y (NPY) or somatostatin antibodies. At variance, neurons immunopositive to parvalbumin or cholecystokinin were not immunopositive to pimonidazole. Pimonidazoleimmunopositive neurons expressed remarkable immunoreactivity to hypoxia-inducible factor 1α (HIF-1α). Interestingly, surgical samples obtained from pharmacoresistant patients showed neurons co-labeled by HIF-1α and NPY antibodies. These interneurons, along with parvalbumin-positive interneurons that were negative to HIF-1α, showed immunopositivity to markers of cell damage, such as high-mobility group box 1 in the cytoplasm and cleaved caspase-3 in the nucleus. These findings suggest that interneurons are continuously endangered in rodent and human epileptogenic tissue. The presence of hypoxia and cell damage markers in NPY interneurons of rats and patients presenting with recurrent seizures indicates a mechanism of selective vulnerability in a specific neuronal subpopulation.

2013 - Lesions to right prefrontal cortex impair real-world planning through premature commitments. [Articolo su rivista]
Goel, V; Vartanian, O; Bartolo, Angela; Hakim, L; Ferraro, Am; Isella, V; Appollonio, I; Drei, S; Nichelli, Paolo Frigio
abstract

While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored)

2013 - New insights into the brain involvement in patients with Crohn’s disease: a voxel-based morphometry study [Articolo su rivista]
A., Agostini; Benuzzi, Francesca; N., Filippini; A., Bertani; A., Scarcelli; Farinelli, Valentina; C., Marchetta; C., Calabrese; F., Rizzello; P., Gionchetti; M., Ercolani; M., Campieri; Nichelli, Paolo Frigio
abstract

Background Crohn’s disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. Methods Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. Key Results With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. Conclusions & Inferences Crohn’s disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.

2013 - Obesity and the Risk of Intracerebral Hemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy. [Articolo su rivista]
Pezzini, A; Grassi, M; Paciaroni, M; Zini, Andrea; Silvestrelli, G; Iacoviello, L; Di Castelnuovo, A; Del Zotto, E; Caso, V; Nichelli, Paolo Frigio; Giossi, A; Volonghi, I; Simone, Am; Lanari, A; Costa, P; Poli, L; Pentore, R; Falzone, F; Gamba, M; Morotti, A; Ciccone, A; Ritelli, M; Guido, D; Colombi, M; De Gaetano, G; Agnelli, G; Padovani, A; on behalf of the Multicentre Study on Cerebral Hemorrhage in Italy, Investigators
abstract

BACKGROUND AND PURPOSE: The effect of obesity on the risk of intracerebral hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further address this issue, we investigated and quantified the correlations between obesity and obesity-related conditions in the causal pathways leading to ICH. METHODS: A total of 777 ICH cases >/= 55 years of age (287 lobar ICH and 490 deep ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy and compared with 2083 control subjects by a multivariate path analysis model. Separate analyses were conducted for deep and lobar ICH. RESULTS: Obesity was not independently associated with an increased risk of lobar ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-1.01) or deep ICH (OR, 1.18; 95% CI, 0.95-1.45) when compared with control subjects. The path analysis confirmed the nonsignificant total effect of obesity on the risk of lobar ICH (OR, 0.77; 95% CI, 0.58-1.02) but demonstrated a significant indirect effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03-1.57), mostly determined by hypertension (OR, 1.07; 95% CI, 1.04-1.11) and diabetes mellitus (OR, 1.04; 95% CI, 1.01-1.07). Obesity was also associated with an increased risk of deep ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14-2.31). CONCLUSIONS: Obesity increases the risk of deep ICH, mostly through an indirect effect on hypertension and other intermediate obesity-related comorbidities, but has no major influence on the risk of lobar ICH. This supports the hypothesis of different, vessel-specific, biological mechanisms underlying the relationship between obesity and cerebral hemorrhage.

2013 - Personality influence processing of social norms judgments. [Poster]
Zucchell, M.; Morlini, S.; Ferrari, E.; Molinari, M. A.; Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

Background: The knowledge of social norms (customary rules that govern behaviour in groups and societies) together with personality dispositions (traits) determines social decision behaviour in individual’s everyday life. Aim of the present fMRI study was to investigate the neural correlates of social norms processing and their bound with personality traits. Methods: Fourteen healthy right-handed subjects (13 female, mean age= 29 yrs) took part in the study. In each of tree runs subjects were presented with written sentences representing 3 different types of situation: 1. description of a behaviour that represents a violation of a social norm (intentional transgression); 21 sentences; 2. description of a normative social behaviour (adaptation of a social norm); 21 sentences; 3. description of a non social behaviour (control condition); 21 sentences. Subjects were asked to indicate whether they would act as described in the sentence or not by pressing one of two buttons. Functional images (TR= 2000) were acquired on a 3T Philips Intera system from 35 axial contiguous 3 mm slices (80 x 80 matrix) and were analyzed using SPM8 with a random effect model. Subject were administered with the BIS/BAS personality questionnaire (1) describing two motivational systems that underlie behaviour: an inhibition system (BIS) regulating aversive motives, in which the goal is to move away from something unpleasant and a behavioural activation system (BAS) regulating appetitive motives, in which the goal is to move toward something. There are three BAS- subscales: The Drive (D) scale pertains to the persistent pursuit of desired goals; the Fun-seeking scale reflects both a desire for new rewards and a willingness to approach a potentially rewarding event on spur of moment; finally Reward Responsiveness (RR) focus on positive responses to the occurrence or anticipation of reward. To test whether personality traits influenced the social norms processing, the BIS/BAS scale and its sub-scale scores were correlated with sBOLD signal changes during the social decision task (violation and adaptation to social norms vs control condition). Results: The processing of social decision (violation and adaptation to social norms) sentences with respect to control sentences evoked extensive bilateral activations mainly in the prefrontal and temporal regions; significant cluster were also found in thalamus and midbrain. No differences were found between the processing of item describing a violation and an adaptation to social norms. The correlation with BIS/BAS questionnaire showed significant BOLD signal changes: BAS-D scores positively correlated with activations of middle and inferior frontal cortex of both hemisphere, left amygdala, right putamen and cerebellum of both side. BAS-RR scores correlated with bilateral activations in superior and middle frontal gyrus, anterior cingulate, middle temporal gyrus and substantia nigra. No significant cluster was found in the correlation with BIS score. Conclusions: fMRI results showed that the neural network subserving social decision making includes an extended activation of the bilateral prefrontal cortex. BAS personality traits influenced the activity of this network. The BAS system governs responses to positive, rewarding stimuli resulting in approach behaviour. This includes the response to happy faces, monetary incentives and the expectancy of reward (2). Our data revealed that BAS high individuals showed an enhanced activity in this reward system suggesting an higher dependency on social approval. On the contrary, BIS system (the inhibition one) seem not to influence the processing of social norms. Summing up, the presents study suggests that personality dispositions are a fundamental source of information for social decision making. Bibliography 1. Carver, C. S., & White, T. L. (1994). Behavioral inhibition, behavioral activation, and affec

2013 - Recurrent varicella following steroids and fingolimod in a Multiple Sclerosis patient [Articolo su rivista]
Ferraro, Diana; DE BIASI, Sara; Vitetta, F; Simone, A. M; Federzoni, Lucia; Borghi, Valentina; Cossarizza, Andrea; Nichelli, Paolo Frigio; Sola, P.
abstract

This is the case report of a multiple sclerosis patient who presented recurrent varicella following steroid and fingolimod therapy

2013 - The impact of clinical factors, riluzole and therapeutic interventions on ALS survival: A population based study in Modena, Italy [Articolo su rivista]
Georgoulopoulou, Eleni; Nicola, Fini; Vinceti, Marco; Marco, Monelli; Paolo, Vacondio; Giorgia, Bianconi; Patrizia, Sola; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded. The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded.

2012 - "My sister's hand is in my bed": a case of somatoparaphrenia. [Articolo su rivista]
Pugnaghi, Matteo; Molinari, M; Panzetti, Patrizia; Nichelli, Paolo Frigio; Zamboni, Giovanna
abstract

Case report of a patient who, after a right thalamic, developed somatoparaphrenia

2012 - Brain air embolism secondary to atrial-esophageal fistula. [Articolo su rivista]
Zini, Andrea; Carpeggiani, P; Pinelli, G; Nichelli, Paolo Frigio
abstract

Case report of a patient who developed a cerebral air embolism secondary to atrial-esophageal fistula.

2012 - Drug-resistant epilepsy after a first unprovoked seizure in adolescence and adulthood: A prospective cohort study [Articolo su rivista]
Monti, G.; Giovannini, G.; Pugnaghi, M.; Mirandola, L.; Nichelli, P.; Meletti, S.
abstract

We present a monocentric prospective study performed on a population of 394 consecutive patients with a first unprovoked seizure evaluated from January 1st 2006 to December 31st 2009 with the purpose to identify the short-term frequency of drug-resistant epilepsy (DRE) in patients with a first seizure in adolescence or adulthood. Drug resistance was determined using two different definitions: (a) Berg, 20061; (b) ILAE, 20102. We identify 18 ILAE DRE patients (6,5%) and 10 (4,5%) Berg DRE patients. Fifteen patients have focal epilepsy (12 symptomatic, 3 cryptogenic); 2 patients have idiopathic generalized epilepsy, one had cryptogenic generalized epilepsy. Three DRE patients had at onset status epilepticus, and all DRE patients had the second seizure within three months from the onset. Conclusion: These results suggest that: (a) epilepsy onset in adolescence/adulthood is associated wit a low percentage (4-7%) of DRE; (b) these patients quickly became drug-resistant, supporting the concept of DRE as expression of intrinsic severity of the disease (Sillanpaa et al, 2009). Early detection of these patients can lead to early epilepsy surgery.

2012 - Emotional experience in mesial temporal lobe epilepsy patients [Articolo su rivista]
Bonora, A.; Benuzzi, F.; Tocchini, S.; Monti, G.; Mirandola, L.; Pugnaghi, M.; Nichelli, P.; Meletti, S.
abstract

Defective social abilities have been observed in patients with Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis (MTLE), particularly in facial expression recognition of negative emotions1-3. The aim of this study was to test the existence of a supramodal system for recognizing signals of fundamental emotions and whether these abilities are linked to the experience of the same emotions. A group of MTLE patients has performed two different tasks: 1) emotions recognition from facial expressions and prosody of five basic emotions (happiness, fear, disgust, anger and sadness); 2) evaluation of subjective experience of emotions of fear, anger and disgust. The results show a significant correlation between facial emotion and emotional prosody recognition tasks, whereas no correlation was found between subjective measures of fear, anger, disgust and the recognition of these emotions in the visual and auditory domain. These preliminary data suggest the existence of a supramodal system for recognizing fundamental emotions and that the neuronal systems involved in the recognition of the visual and prosodic expression of emotion may not be necessary for the subjective experience.

2012 - Fear and happiness in the eyes: an intra-cerebral event-related potential study from the human amygdala. [Articolo su rivista]
Meletti, Stefano; G., Cantalupo; Benuzzi, Francesca; R., Mai; L., Tassi; Gasparini, Elisa; C. A., Tassinari; Nichelli, Paolo Frigio
abstract

We present the response pattern of intracranial event-related potentials (ERPs) recorded from depth-electrodes in the human amygdala (four patients) to faces or face parts encoding fearful, happy or neutral expressions. The amygdala showed increased amplitude ERPs (from 200 to 400ms post-stimulus) in response to the eye region of the face compared to whole faces and to the mouth region. In particular, a strong emotional valence effect was observed, both at group and at single-subject level, with a preferential response to fearful eyes respect to every other stimulus category from 200 to 400ms after stimulus presentation. A preferential response to smiling eyes compared to happy faces and smiling mouths was also observed at group level from 300 to 400ms post-stimulus presentation. A complementary time-frequency analysis was performed showing that an increase in the theta frequency band (4-7Hz) accounted for the main event-related band power (ERBP) change during the 200-500ms post stimulus interval. The analysis of the ERBPs changes according to their emotional valence showed a strong increase in theta ERBP to fearful eyes, which was higher respect to any other facial stimulus. Moreover, theta ERBP increase to "smiling eyes" was larger respect with that evoked by smiling mouths and whole happy faces. Minimal post-stimulus ERBPs changes were evoked by neutral stimuli. These data are consistent with a special role of the amygdala in processing facial signals, both with negative and positive valence, conveyed by the eye region of the face.

2012 - Ictal involvement of the nigrostriatal system in subtle seizures of ring chromosome 20 epilepsy. [Articolo su rivista]
Meletti, Stefano; Vignoli, A; Benuzzi, Francesca; Avanzini, P; Ruggieri, A; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Canevini, M. P.
abstract

Studies in animal models and patients with epilepsy have suggested that basal ganglia circuits may control epileptic seizures and that striatal dopaminergic transmission may play a role in seizure modulation and interruption. Chromosome 20 [r(20)] syndrome is a well-defined chromosomal disorder characterized by epilepsy, mild-to-moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, with prolonged episodes of nonconvulsive status epilepticus suggesting dysfunction in the seizure control system. We present the ictal blood oxygen level-dependent (BOLD) changes in brief seizures recorded by means of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration in a patient with [r(20)] syndrome. We observed ictal BOLD increments in a cortical-subcortical network involving substantia nigrastriatum and frontal cortex. At present, this is the first functional neuroimaging evidence of the involvement of the nigrostriatal system during ictal EEG discharges in [r(20)] syndrome supporting a role of the basal ganglia circuits in human epileptic seizures.

2012 - Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies. [Articolo su rivista]
Benuzzi, Francesca; Mirandola, Laura; Pugnaghi, Matteo; Farinelli, Valentina; C. A., Tassinari; G., Capovilla; G., Cantalupo; F., Beccaria; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Purpose:  Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so-called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level-dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset. Methods:  Twenty-one patients with IGE underwent EEG-fMRI coregistration. EEG-related analyses were run both at the single-subject and at group level (random effect). The time-course analysis was conducted for 3 s time windows before, during, and after GSWDs, and they were included until no further BOLD signal changes were observed. Key Findings:  Fifteen patients (nine female, mean age 28 years) had GSWDs during EEG-fMRI coregistration (262 total events, mean duration 4 s). Time-course group analysis showed BOLD increments starting approximately 10 s before GSWD onset located in frontal and parietal cortical areas, and especially in the precuneus-posterior cingulate region. At GSWD onset, BOLD increments were located in thalamus, cerebellum, and anterior cingulate gyrus, whereas BOLD decrements were observed in the DMN regions persisting until 9 s after onset. Significance:  Hemodynamic changes (BOLD increments) occurred in specific cortical areas, namely the precuneus/posterior cingulate, lateral parietal, and frontal cortices, several seconds before EEG onset of GSWD. A dysfunction of these brain regions, some of which belongs to the DMN, may be crucial in generating GSWDs in patients with IGE.

2012 - Internal carotid artery dissection: a rare cause of peripheral facial nerve palsy [Articolo su rivista]
Fioravanti, Valentina; Vinceti, Giulia; Chiari, Annalisa; Canali, Elena; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

NA

2012 - Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study. [Articolo su rivista]
Paciaroni, M; Agnelli, G; Caso, V; Pieroni, A; Bovi, P; Cappellari, M; Zini, Andrea; Nichelli, Paolo Frigio; Inzitari, D; Nesi, M; Nencini, P; Pezzini, A; Padovani, A; Tassinari, T; Orlandi, G; Chiti, A; Gialdini, G; Alberti, A; Venti, M; Acciarresi, M; D'Amore, C; Luda, E; Tassi, R; Martini, G; Ferrarese, C; Beretta, S; Trentini, C; Silvestrelli, G; Lanari, A; Previdi, P; Ciccone, A; Delodovici, Ml; Bono, G; Galletti, G; Marcheselli, S; Del Sette, M; Traverso, E; Riva, M; Silvestrini, M; Cerqua, R; Consoli, D; Monaco, S; Toni, D.
abstract

BACKGROUND AND PURPOSES: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. METHODS: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. RESULTS: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days. CONCLUSIONS: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome

2012 - Lack of attentional resources modulation in chronic stress: an fMRI study on Crohn’s disease. [Poster]
Benuzzi, Francesca; Agostini, A.; Zucchelli, M.; Farinelli, Valentina; Filippini, N.; Campieri, M.; Nichelli, Paolo Frigio
abstract

Introduction: Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. In CD patients, chronic perceived psychological stress may increase the incidence of symptoms and of subsequent disease relapses (Mawdsley et al. 2005; Agostini et al. 2010). To test whether psychological stress in CD is related to abnormal brain activity, we used fMRI to compare brain network modulated by cognitive stress in CD patients and in healthy controls. Methods: Eighteen right-handed CD patients (10 female; mean age= 32 yrs ) and eighteen right-handed healthy controls (11 female; mean age= 28 yrs ) underwent a block fMRI study. The functional protocol consisted in two repeated runs, each comprised of 3 blocks of the Stroop colour-word test (Stroop 1935).Three blocks of a control condition (i.e. colour and word meaning were identical) were also included. Task difficulty and hence its stressfulness was manipulated decreasing the stimulus presentation time over the three different blocks (1500, 1300, and 1100 ms, respectively). A conventional analysis was used to test the attentional effect (Stroop task vs control condition). Furthermore, in order to compare stressor-evoked changes between groups, a parametric analysis was performed using the percentages of correct responses as a regressor. Data were acquired with a Philips Achieva system at 3T. Thirty axial slices were acquired (in-plane matrix: 80x80; TR: 2000 ms; slices 3mm each with a 1mm gap; voxel size: 3x3x4 mm TR = 2000 ms; 3 runs, 240 volumes each). Data analysis was carried out using the SPM5 package. Results: Behavioral data (accuracy and reaction times) did not shown any significant differences between patients and controls. As to functional data, the main activated regions for the Stroop task included the dorsolateral prefrontal cortex as well as the inferior parietal cortex on the left side for both groups. In the parametric analysis, controls showed activation that positively correlated with response accuracy in a bilateral neural network comprising the posterior cingulate, the parahippocampal and the lingual gyri (Figure 1). No specific activation was found for the CD group in the parametric analysis.Conclusions: In healthy subjects, the successful monitoring of the stressful/attentional task was positively related to the activity of a bilateral posterior network. These areas are part of the system responsible for the executive aspects of attentional selection (Banich et al. 2000), which imposes an attentional ''set'' for the task-relevant information- that is, which sets a top-down bias for selecting certain types of information (e.g., color). Despite a good performance in the Stroop task, no correlation pattern with the behavioural data was found in CD patients: no brain region selctively increased its functional activity as accuracy increased, thus suggesting an impaired modulation of the resources needed to perform the task. Further research will be necessary to find out whether abnormal activity in this brain network may be the link between the psychological stress and inflammatory exacerbations.References Agostini, A., et al. (2010). "Parental bonding and inflammatory bowel disease." Psychosomatics 51(1): 14-21. Banich, M. T., et al. (2000). "fMri studies of Stroop tasks reveal unique roles of anterior and posterior brain systems in attentional selection." Journal of Cognitive Neuroscience 12(6): 988-1000. Mawdsley, J. E., et al. (2005). "Psychological stress in IBD: new insights into pathogenic and therapeutic implications." Gut 54(10): 1481-91. Stroop, J. A. (1935). "Studies of interference in serial verbal reactions." Journal of Experimental Psychology 18: 643–662.

2012 - Oral Lacosamide as treatment option in a case of aphasic status epilepticus with continuous spike-and-wave discharges of the adult [Articolo su rivista]
Mirandola, L.; Monti, G.; Bonora, A.; Pugnaghi, M.; Benuzzi, F.; Vinceti, G.; Zucchelli, M.; Nichelli, P.; Meletti, S.
abstract

We present a case report of a 58 year-old man who suffered from simptomatic focal epilepsy due to artero-venous malformation localized in the left superior temporal gyrus. After the excision of the lesion he developed drugresistant epilepsy with temporal seizures characterized by behavioral arrest, automatisms, and aphasia. Despite numerous attempts with different AEDs (CBZ, PHT, LEV) the patient presented monthly seizures. He was admitted to our Department for non-convulsive status epilepticus, clinically characterized by aphasia and confusion, associated to continuous spikes and wave discharges over the fronto-temporal derivations of the left hemisphere. CBL and VPA were added to his therapy, while LEV was suspended for marked irritability. His language disturbance continued to be severe and he underwent neuropsychological evaluation and language fMRI, which documented complex language disorder. Only after gradually introducing oral Lacosamide the patient improved significantly. At 6 months follow-up he no longer experienced recurrent seizures, his EEG was free from epileptiform abnormalities and the aphasia was partially improved, too. We suggest that oral Lacosamide can be a therapeutic option for non convulsive status epilepticus.

2012 - Paroxysmal ventricular tachicardia and pure right insular stroke. [Articolo su rivista]
Zini, Andrea; Fioravanti, Valentina; Ferraro, Diana; Casoni, Federica; Cavazzuti, Milena; Nichelli, Paolo Frigio
abstract

Case report of a patient who developed a paroxysmal ventricular tachicardia after an ischemic stroke limited to the right insula.

2012 - Sensory Loss Mimicking Cauda Equina Syndrome due to Cervical Spinal Lesion in a Patient with Clinically Isolated Syndrome [Articolo su rivista]
Vinceti, Giulia; Zini, Andrea; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

We describe the case of a 39-year-old woman with signs and symptoms suggesting cauda equina syndrome. Lumbosacral magnetic resonance imaging (MRI) demonstrated no lesion at this level, while cervical MRI showed a T2-hyperintense lesion in the middle-right anterolateral region of the cervical spinal cord, which may explain the symptoms by involving the anterior spinothalamic tract. We suggest that in cases with cauda equina syndrome presentation and normal lumbosacral MRI, a cervicodorsal lesion should be considered during diagnostic assessment.

2012 - Structural MRI changes detectable up to ten years before clinical Alzheimer's disease [Articolo su rivista]
Tondelli, Manuela; G. K., Wilcock; Nichelli, Paolo Frigio; C. A., De Jager; M., Jenkinson; Zamboni, Giovanna
abstract

Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.

2012 - Translocation of the embodied self without visuospatial neglect [Articolo su rivista]
Venneri, Annalena; R., Pentore; M., Cobelli; Nichelli, Paolo Frigio; M. F., Shanks
abstract

This is the case report of RB,a 68-year-old retired woman who,following an extensive right sided ischaemic stroke,showed hemiplegia,anosognosia and allochiria,but no somato-sensory deficits and no visuospatial neglect. A high resolution 3D MRI structural scan of her brain was acquired to define the structural damage in detail. Morphometric analyses of grey and white matter data revealed a large lesion which involved most of her right parietal,temporal,and mesial frontal cortex,with partial sparing of the right dorsolateral prefrontal cortex and part of the posterior corpus callosum. Detailed examination showed that RB attributed sensory stimuli,both on the left and on the right,to the opposite side of her body. This mirror reversed representation of her body caused misattribution of items even in the absence of stimulation,as for instance when the patient spontaneously reported pain in her right knee while pointing to her left knee. RB's neuropsychological profile showed normal or borderline performance on most cognitive tasks. Language comprehension was intact and she could tell left from right without difficulty in all instances except for those referable to her soma. To our knowledge this is the first description of severe allochiria for body representation in the absence of neglect. The evidence from this case supports the developing concept that the body representation is not simply a systematic registration of proprioceptive inputs,but that the brain has a more sophisticated high level representation of one's body map which is updated on the basis of multimodal information.

2012 - Ventral and Dorsal Stream Dissociation During Action Recognition in the Human Brain. [Poster]
Handjaras, G.; Bernardi, G.; Benuzzi, Francesca; Nichelli, Paolo Frigio; Pietrini, P.; Ricciardi, E. .
abstract

Introduction. According to the perception-action framework [4], the ventral stream mediates object recognition, while the dorsal stream processes the sensory control of object-directed actions. The existence of two functionally independent visual streams [3], however, is debated [8]. To determine whether such a pure functional dissociation exists, or rather an integration of action-object representations occurs in the ventral and dorsal streams, we used a Multi Voxel Pattern Analysis to examine whether neural patterns of visually perceived hand-mediated actions differed on the basis of the object class being manipulated. Methods. We used an fMRI (Philips 3T; TR 2.5s; 3x3x3 mm voxel size) six-run slow event-related design to examine neural activity in 14 right-handed healthy volunteers while they watched 3s-long videos that randomly alternated between different types of human hand-made, object-directed actions or environmental scenes with 7s of ISI. A first set of stimuli depicted ‘tool-mediated’ (e.g. hammering a nail, cutting with scissors), ‘intransitive’ (e.g. clapping, ok gesture) and ‘distal transitive’ (e.g. opening a jar, grabbing) actions. A second set consisted of videos reproducing three fixed motor acts (‘pushing away’, ‘grasping-to-lift’, ‘putting down’) performed with ‘animate’ and ‘inanimate’ objects. After standard processing using AFNI [1], BOLD responses to each stimulus of the first set were used in a 3-class Support Vector Machine (SVM) classifier [6] with an additional Recursive Feature Elimination algorithm [2]. Then, the discriminative voxels of this classifier responding to action features were isolated into ventral occipito-temporal [5] and dorsal parietal regions of interest (ROIs). Inside these ROIs, the patterns of BOLD response elicited by the second set of action stimuli were compared to each other and to those elicited by environmental scenes to obtain a representational dissimilarity matrix (RDM) using the 1-r Pearson coefficient [7]. A hierarchical clustering procedure was derived from the RDM to create a dendrogram. Moreover, we used multi-class SVM classifiers to assess the uncertainty in cluster analysis. Accuracy (Acc) values of the classifiers were tested as significantly different from chance by a permutation test. Results. The SVM classifier, trained on the first set of stimuli, was able to distinguish between ‘tool-mediated’, ‘intransitive’ and ‘distal transitive’ actions with an Acc of 73.3% (p<0.0025). The discriminative map [Fig 1] relied on an inferior frontal, premotor, inferior parietal and temporal cortical network, and included brain areas mainly within the human mirror system [9]. Using the second set of actions, as expected, environmental scenes were clearly separated from actions in both ROIs (Acc 92%, p<0.0025). Within the inferior temporal ROI, the RDM showed a significant distinction between the two classes of objects only (‘animate’ vs. ‘inanimate’, Acc 69.7%, p<0.0025) but was unable to recognize the different actions [Fig 2]. Using the parietal ROI, we found a significant distinction between three classes of actions (‘pushing’ vs. ‘grasping’ vs. ‘putting’ acts, Acc 39.8%, p<0.05) and between the two classes of objects (‘animate’ vs. ‘inanimate’, Acc 58.3%, p<0.05) [Fig 3]. Conclusions. In line with previous findings [7], action stimuli were processed in the ventral stream accordingly to the recognition of object features (specifically, ‘animate’ and ‘inanimate’ properties), even when the represented object was included within more complex action scenes. The dorsal stream was able to discriminate both different classes of motor acts and object features, suggesting a more complex analysis of the relationship between objects and actions. In conclusion, our results suggest that the functional dissociation between the ventral and dorsal streams may be less absolute than pre

2012 - miRNAs expression analysis in paired fresh/frozen and dissected formalin fixed and paraffin embedded glioblastoma using real-time pCR [Articolo su rivista]
de Biase, D; Visani, M; Morandi, L; Marucci, G; Taccioli, C; Cerasoli, S; Baruzzi, A; Pession, A; Albani, F; Calbucci, F; D'Alessandro, R; Michelucci, R; Brandes, A; Eusebi, V; Ceruti, S; Fainardi, E; Tamarozzi, R; Emiliani, E; Cavallo, M; Franceschi, E; Tosoni, A; Cavallo, M; Fiorica, F; Valentini, A; Depenni, R; Mucciarini, C; Crisi, G; Sasso, E; Biasini, C; Cavanna, L; Guidetti, D; Marcello, N; Pisanello, A; Cremonini, Am; Guiducci, G; de Pasqua, S; Testoni, S; Agati, R; Ambrosetto, G; Bacci, A; Baldin, E; Baldrati, A; Barbieri, E; Bartolini, S; Bellavista, E; Bisulli, F; Bonora, E; Bunkheila, F; Carelli, V; Crisci, M; Dall'Occa, P; Ferro, S; Franceschi, C; Frezza, G; Grasso, V; Leonardi, M; Mostacci, B; Palandri, G; Pasini, E; Pastore Trossello, M; Poggi, R; Riguzzi, P; Rinaldi, R; Rizzi, S; Romeo, G; Spagnolli, F; Tinuper, P; Trocino, C; Dall'Agata, M; Faedi, M; Frattarelli, M; Gentili, G; Giovannini, A; Iorio, P; Pasquini, U; Galletti, G; Guidi, C; Neri, W; Patuelli, A; Strumia, S; Casmiro, M; Gamboni, A; Rasi, F; Cruciani, G; Cenni, P; Dazzi, C; Guidi, Ar; Zumaglini, F; Amadori, A; Pasini, G; Pasquinelli, M; Pasquini, E; Polselli, A; Ravasio, A; Viti, B; Sintini, M; Ariatti, A; Bertolini, F; Bigliardi, G; Carpeggiani, P; Cavalleri, F; Meletti, Stefano; Nichelli, Paolo Frigio; Pettorelli, E; Pinna, G; Zunarelli, E; Artioli, F; Bernardini, I; Costa, M; Greco, G; Guerzoni, R; Stucchi, C; Iaccarino, C; Ragazzi, M; Rizzi, R; Zuccoli, G; Api, P; Cartei, F; Fallica, E; Granieri, E; Latini, F; Lelli, G; Monetti, C; Saletti, A; Schivalocchi, R; Seraceni, S; Tola, Mr; Urbini, B; Giorgi, C; Montanari, E; Cerasti, D; Crafa, P; Dascola, I; Florindo, I; Giombelli, E; Mazza, S; Ramponi, V; Servadei, F; Silini, Em; Torelli, P; Immovilli, P; Morelli, N; Vanzo, C; Nobile C., PERNO Study Group
abstract

miRNAs are small molecules involved in gene regulation. Each tissue shows a characteristic miRNAs epression profile that could be altered during neoplastic transformation. Glioblastoma is the most aggressive brain tumour of the adult with a high rate of mortality. Recognizing a specific pattern of miRNAs for GBM could provide further boost for target therapy. The availability of fresh tissue for brain specimens is often limited and for this reason the possibility of starting from formalin fixed and paraffin embedded tissue (FFPE) could very helpful even in miRNAs expression analysis. We analysed a panel of 19 miRNAs in 30 paired samples starting both from FFPE and Fresh/Frozen material. Our data revealed that there is a good correlation in results obtained from FFPE in comparison with those obtained analysing miRNAs extracted from Fresh/Frozen specimen. In the few cases with a not good correlation value we noticed that the discrepancy could be due to dissection performed in FFPE samples. To the best of our knowledge this is the first paper demonstrating that the results obtained in miRNAs analysis using Real-Time PCR starting from FFPE specimens of glioblastoma are comparable with those obtained in Fresh/Frozen samples.

2011 - A case of late onset drug-resistant epilepsy associated with chronic Epstein-Barr virus encephalitis [Articolo su rivista]
Monti, G.; Pugnaghi, M.; Nichelli, P.; Meletti, S.
abstract

Drug resistant epilepsies represent 25% of epilepsies and lead to a debilitating prognosis with low quality of life. This requires a correct diagnosis in each patients to verify the real drug-resistance. We describe a case of a old woman that began presenting seizure at age of 70. For several years the patient was treated for a cryptogenic drug resistant epilepsy. She presented also a cognitive decline and loss of autonomy. After a prolonged post-ictal state the patient was admitted to our department and we investigated the possible causes with several tests. The EEG was characterized by spread slow waves. MRI excluded acute events. We found a CSF positivity for EBV PCR. We started Acyclovir and steroids with a rapid clinical and EEG improvement. After a follow up of 6 month the patient is seizure free.

2011 - Can HIV infection cause a worsening of tics in Tourette patients? [Articolo su rivista]
F., Antonelli; V., Borghi; G., Galassi; Nichelli, Paolo Frigio; F., Valzania
abstract

This is a case report of a patient of worsening of tics in a Tourette patients after HIV infection

2011 - Changing incidence and subtypes of ALS in Modena, Italy: A 10-years prospective study [Articolo su rivista]
Georgoulopoulou, Eleni; Vinceti, Marco; F., Bonvicini; P., Sola; C. A., Goldoni; G. D., Girolamo; Ferraro, Diana; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

We performed a prospective population-based study to describe the temporal pattern of the incidence and prevalence and the clinical features and phenotypes of ALS in Modena, Italy, from 2000 to 2009. From 2000 onwards, a prospective registry has been collecting all cases of incident ALS among residents in the province of Modena. This source was implemented by cases resulting from the provincial hospitals, and by death certificates. Based on 193 newly diagnosed cases, the crude average annual incidence rate of ALS was 2.9 cases per 100,000 person years (py); adjusted incidence rate was 2.8/100,000. The age-standardized incidence rates increased from 2.6 per 100,000 py in 2000-2004 to 2.9 per 100,000 py in 2005-2009, representing an annual increase of approximately 2% throughout the 10-year period. There was a constant increase in prevalence rates throughout the years of the study (from 5.8/100,000 on 31 December 2000 to 11.2/100,000 on 31 December 2009). Median life time was 29 months for patients diagnosed before the year 2000 and 36 months for patients diagnosed from 1 January 2000 (p < 0.01). Thus, we report incidence rates similar to those reported by recent European population based studies, but we observed an increasing trend over the 10 years of the study. The increasing incidence is not explained by aging of the population, and our study raises the question as to whether local environmental or genetic factors are driving this temporal trend. Along with an increasing incidence, we found an important increase in prevalence and survival probably related to access to mutidisciplinary clinics and improvements in symptomatic care of ALS.

2011 - Combining neuropsychological and structural neuroimaging indicators of conversion to Alzheimer's Disease in Amnestic Mild Cognitive Impairment [Articolo su rivista]
Venneri, Annalena; G., Gorgoglione; C., Toraci; L., Nocetti; Panzetti, Patrizia; Nichelli, Paolo Frigio
abstract

Morphometric and neuropsychological retrospective studies of amnestic mild cognitive impairment (MCI) have demonstrated that regional atrophies and cognitive impairments may differentiate stable from progressing MCI. No measure has proved helpful prospectively. In this study, twenty five amnestic MCI patients and 25 healthy controls underwent structural MRI and comprehensive neuropsychological assessment. The groups' grey matter volumes were compared with voxel based morphometry and were also correlated with scores obtained on paired associates learning and category fluency tasks. MCI patients had significantly reduced grey matter volume in left mediotemporal and other neocortical regions compared with controls. Atrophy in perirhinal and anterior inferior temporal cortex was associated with poor scores on both category fluency and paired associates learning tasks. After 36 months, 44% of the MCI sample converted to dementia. Converter and non-converter MCI subgroups differed in paired associates learning and in category fluency scores, and showed limited differences in grey matter loss in the hippocampal complex. Variable atrophy in the hippocampus was not a relevant element in the converter/non converter distinction, but converters had significant volumetric reductions in the perhirinal cortex and in other anterior temporal and frontal neocortical areas. A high proportion of converters (91%) could be identified from baseline data using a combination of measures of regional atrophy in left temporal association cortex and poor scores on paired associates learning and category fluency tasks. This combined approach may offer a better option than using each measure alone to prospectively identify individuals at more immediate risk of conversion to dementia in the MCI population. The clinical advantage of this combination of structural MRI and neuropsychological measures in predicting conversion to dementia will need additional prospective validation.

2011 - DRUG-RESISTANT EPILEPSY AFTER A FIRST UNPROVOKED SEIZURE IN ADOLESCENCE AND ADULTHOOD: A PROSPECTIVE COHORT STUDY [Abstract in Rivista]
Monti, Giulia; Giovannini, Giada; Pugnaghi, Matteo; Mirandola, Laura; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2011 - EMOTIONAL EXPERIENCE AND EMOTION RECOGNITION IN MESIAL TEMPORAL LOBE EPILEPSY PATIENTS [Abstract in Rivista]
A., Bonora; Meletti, Stefano; S., Tocchini; Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

2011 - FIRST UNPROVOKED SEIZURE 1-YEAR MORTALITY: A MONOCENTRIC PROSPECTIVE COHORT STUDY [Abstract in Rivista]
Giovannini, Giada; Monti, Giulia; Mirandola, Laura; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2011 - I disturbi emozionali associati a malattie neurologiche. [Capitolo/Saggio]
Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

Le emozioni sono risposte complesse dell’organismo a stimoli adeguati, che si manifestano con specifici repertori di azioni e con modificazioni dello stato interno, che possiamo osservare e misurare. In questo capitolo prenderemo in esame come si modifica la percezione e l’espressione delle emozioni in seguito a specifiche lesioni o malattie neurologiche. Studiando il riconoscimento delle espressioni emozionali del volto, è stato possibile dimostrare che il riconoscimento di alcune espressioni può essere colpito in modo selettivo. Ciò dimostra che non esiste un unico «centro» o un unico «circuito» per le emozioni, ma che diverse strutture entrano in gioco per rappresentare la percezione di diverse emozioni e le risposte collegate.

2011 - Isolated progressive cognitive impairment and depression in a patient with neuroradiological features suggestive of multiple sclerosis [Articolo su rivista]
Ferraro, Diana; Simone, ANNA MARIA; Merelli, E.; Mandrioli, J:; Molinari, M. A.; Nichelli, Paolo Frigio; Sola, P.
abstract

We report the case of a woman who started complaining of depression, attention and memory problems at the age of 49. Over the following 6 years, serial neuropsychological assessments showed fluctuating, but overall progressively worsening, performances in tests exploring attention, working memory, language and executivefunctions. Cerebrospinal fluid (CSF) examination showed identical IgG oligoclonal bands in serum and CSF.Neurological examination, to date, only reveals minimal pyramidal and cerebellar signs. Although typical clinical and laboratory evidence indicating a diagnosis of multiple sclerosis (MS) in this patient is lacking, an extensive diagnostic work-up ruled out many other causes of leukoencephalopathy and neuroradiological features strongly suggest this diagnosis. Multiple sclerosis may present with cognitive or neuropsychiatric symptoms; this should be kept in mind, especially in younger patients, even in the absence of ‘‘classical’’ physical symptoms.

2011 - Non convulsive status epilepticus of frontal origin as the first manifestation of Haschimoto's encephalopathy [Articolo su rivista]
Monti, Giulia; Pugnaghi, Matteo; A., Ariatti; Mirandola, Laura; Giovannini, Giada; S., Scacchetti; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto's encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a form of non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis.

2011 - POSITIVE BOLD RESPONSE IN THE BRAIN'S DEFAULT MODE NETWORK ANTICIPATES SPIKE AND WAVE DISCHARGES IN IDIOPATHIC GENERALIZED EPILEPSY [Abstract in Rivista]
Mirandola, Laura; Benuzzi, Francesca; Pugnaghi, Matteo; V., Farinelli; Tassinari, C. A.; G., Capovilla; G., Cantalupo; F., Beccaria; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2011 - Primary progressive versus relapsing-onset multiple sclerosis: presence and prognostic value of cerebrospinal fluid oligoclonal IgM [Articolo su rivista]
P., Sola; Mandrioli, Jessica; Simone, ANNA MARIA; Ferraro, Diana; Bedin, Roberta; R., Annecca; Venneri, Maria Grazia; Nichelli, Paolo Frigio; E., Merelli
abstract

Background: There is increasing evidence on cerebrospinal fluid (CSF) oligoclonal IgM (OCIgM) predicting a more aggressive disease course in relapsing-remitting Multiple Sclerosis (MS), while there is a scarcity of data for primary progressive MS (PPMS). Objective: Our aim was to investigate the presence and possible prognostic value of CSF OCIgM in a group of PPMS and in a group of relapsing-onset MS patients. The possible prognostic role of other clinical and biological factors was also evaluated. Methods: We calculated the impact of single clinical and biological factors, including CSF OCIgM at onset, on the probability of reaching an Expanded Disability Status Scale of 3 and 4 in 45 PPMS and 104 relapsing-onset MS patients. Results: CSF OCIgM were found in only 13% of PPMS patients and did not influence the time taken to reach an Expanded Disability Status Scale of 3 and 4. Conversely, they were present in 46% of relapsing-onset MS patients and increased the risk of reaching an Expanded Disability Status Scale of 4. Clinical factors with a negative prognostic value in PPMS were age at onset <30 years and onset with pyramidal symptoms, while onset with sensory symptoms in relapsing-onset MS predicted a more favourable course. Conclusion: This study confirms that, in relapsing-onset MS patients, the presence of CSF OCIgM at onset predicts a worse disease course. In the cohort of PPMS patients, however, CSF OCIgM were rare, suggesting that heterogeneous pathogenetic mechanisms may be involved in the different MS forms.

2011 - Recognition of emotions from faces and voices in medial temporal lobe epilepsy [Articolo su rivista]
A., Bonora; Benuzzi, Francesca; Monti, Giulia; L., Mirandola; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Patients with chronic medial temporal lobe epilepsy (MTLE) can be impaired in different tasks that evaluate emotional or social abilities. In particular, the recognition of facial emotions can be affected (Meletti S, Benuzzi F, Rubboli G, et al. Neurology 2003;60:426-31. Meletti S, Benuzzi F, Cantalupo G, Rubboli G, Tassinari CA, Nichelli P. Epilepsia 2009;50:1547-59). To better understand the nature of emotion recognition deficits in MTLE we investigated the decoding of basic emotions in the visual (facial expression) and auditory (emotional prosody) domains in 41 patients. Results showed deficits in the recognition of both facial and vocal expression of emotions, with a strong correlation between performances across the two tasks. No correlation between emotion recognition and measures of IQ, quality of life (QOLIE-31), and depression (Beck Depression Inventory) was significant, except for a weak correlation between prosody recognition and IQ. These data suggest that emotion recognition impairment in MTLE is not dependent on the sensory channel through which the emotional stimulus is transmitted. Moreover, these findings support the notion that emotional processing is at least partly independent of measures of cognitive intelligence.

2011 - The Neuroanatomical Substrate of Lexical-Semantic Decline in MCI APOE epsilon4 Carriers and Noncarriers [Articolo su rivista]
Venneri, Annalena; W. J., Mcgeown; R., Biundo; Mion, Marco; Nichelli, Paolo Frigio; M. F., Shanks
abstract

Lexical-semantic competency in mild cognitive impairment (MCI) epsilon4 carriers was used as an endophenotype, and gray matter volume in MCI epsilon4 carriers/noncarriers and in noncarrier controls was compared. Residual gray matter volumes were correlated with age of acquisition values for words from a category fluency task, an index of semantic competency. MCI patients had significantly impoverished lexical-semantic output compared with controls, more marked in MCI epsilon4 carriers. Smaller volumes in the left hippocampus, bilateral regions of the uncus, and posterior cingulate cortex were associated with a tendency to retrieve earlier acquired words in the category fluency task in MCI epsilon4 carriers, whereas poor semantic performance in MCI noncarriers was associated with smaller volumes in the left uncus, bilateral regions of the parahippocampal gyrus, and hippocampus, and also in a large number of neocortical regions. There was a significant semantic competency by genotype interaction in the left perirhinal cortex, in a number of left frontal and temporal areas and in the right inferior parietal lobule and precuneus. MCI epsilon4 carriers, when compared with noncarriers, had lower gray matter volume values confined to the right precuneus and the cerebellum bilaterally, but the converse comparison showed that MCI noncarriers had lower values in extensive frontal, temporal, and parietal regions of the neocortex. Similar brain volumetric variations linked to genotype were found in minimal-to-mild AD. The results suggest a relatively specific impact of apolipoprotein E (APOE) epsilon4 burden and underline the value of linguistic assessment in preclinical diagnosis.

2011 - The role of emotions in decisional processes: How neuroscience can impact evaluation of patients' ability to will and to act [Articolo su rivista]
Nichelli, P.; Molinari, M.; Benuzzi, F.
abstract

2010 - Comment on 'Huntington's disease presenting as ALS' [Articolo su rivista]
Mandrioli, Jessica; Bernabei, Chiara; Georgoulopoulou, Eleni; Nichelli, Paolo Frigio; Cortelli, Pietro; Tupler, Rossella; E., Signaroldi; P., Sola
abstract

This is a case report of patient with concurrent Huntington disease and Amyotrophic Lateral Sclerosis

2010 - EMOTION RECOGNITION IN MEDIAL TEMPORAL LOBE EPILEPSY IN THE VISUAL AND AUDITORY DOMAIN [Abstract in Rivista]
Monti, Giulia; A., Bonora; Benuzzi, Francesca; E., Gasparini; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2010 - Focal sensory-motor status epilepticus in multiple sclerosis due to a new cortical lesion. An EEG-fMRI co-registration study. [Articolo su rivista]
E., Gasparini; Benuzzi, Francesca; Pugnaghi, Matteo; A., Ariatti; P., Sola; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

A case of focal inferior limb sensory-motor status epilepticus as the only manifestation of a multiple sclerosis (MS) relapse is described. To obtain evidence of the relationship between the seizures, the cortical plaque and the left foot motor area, an EEG-fMRI co-registration study was undertaken demonstrating that seizure-related BOLD signal substantially overlapped with the inflammatory lesion involving the foot sensory-motor cortex. Seizures did not respond to intravenous anti-epileptic drugs (AEDs) but were controlled by steroid therapy.

2010 - MAKING PLANS AND DECISIONS IN PATIENTS WITH SLEEP-RELATED HYPERMOTOR SEIZURES [Abstract in Rivista]
A., Bonora; M. A., Molinari; Monti, Giulia; Benuzzi, Francesca; E., Gasparini; Pugnaghi, Matteo; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2010 - Primary progressive multiple sclerosis and generalized myasthenia gravis: an uncommon association [Articolo su rivista]
Bigliardi, Guido; Mandrioli, Jessica; F., Valzania; Nichelli, Paolo Frigio; N., Casula; Simone, ANNA MARIA; P., Sola
abstract

The co-occurrence of myasthenia gravis (MG) and multiple sclerosis (MS) is rare, and in all the described cases MS had a relapsing-remitting course and the diseases had a benign clinical evolution. We describe herewith a patient with primary progressive MS (PPMS) and generalized MG with severe clinical course. This is the first report on a case of PPMS associated to MG. Studies on the histology and pathogenesis show that neurodegeneration is predominant over inflammation in PPMS, even if cellular and humoral immune-mediated mechanisms are thought to maintain a crucial importance in the development and progression of this form of disease. In the present case, the detection of cerebrospinal fluid IgM oligoclonal bands support the hypothesis of a possible role of antibody-mediated immunity in PPMS and suggest that humoral immunity may take part in the concomitant development of both MS and MG.

2010 - Rapidly progressive amyotrophic lateral sclerosis in a young patient with hereditary neuropathy with liability to pressure palsies [Articolo su rivista]
Canali, Elena; Chiari, Annalisa; P., Sola; Fioravanti, Valentina; F., Valzania; R., Pentore; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

We describe the rare case of a young woman with hereditary neuropathy with liability to compression palsy (HNPP), who developed a rapidly progressive ALS. We suggest that underexpression of PMP22 protein in the nervous system might interfere with motor neuron function by impairing myelin formation and exposure of the axon to injury. Patients with ALS and evidence of demyelination should be screened for HNPP.

2010 - Test di Stroop: Dati normativi italiani di una versione cartacea per l'uso clinico [Articolo su rivista]
S., Valgimigli; R., Padovani; Budriesi, Carla; M. E., Leone; D., Lugli; Nichelli, Paolo Frigio
abstract

Il compito di Stroop è un paradigma classico della psicologia sperimentale ampiamente utilizzato nell’ambito della neuropsicologia clinica come strumento di misura dell’attenzione selettiva, in particolare dei processi di inibizione delle informazioni irrilevanti. Scopo di questo studio è fornire la taratura nella popolazione italiana di una versione cartacea del test di Stroop maneggevole per l’impiego clinico anche in funzione della rilevazione di un’unica misura di interferenza (numero di stimoli corretti nell’unità di tempo). È stato reclutato un campione di 160 adulti sani distribuiti uniformemente per età (18-77 anni), scolarità e sesso; la normalizzazione dei punteggi è stata effettuata mediante la trasformazione in punteggi equivalenti per permettere la comparazione diretta con altre prove neuropsicologiche che utilizzano la medesima metodica

2009 - Age-related decline in mentalizing skills across adult life span [Articolo su rivista]
M., Pardini; Nichelli, Paolo Frigio
abstract

In the literature, there are few and conflicting reports regarding age-related changes in adult mentalizing abilities: whereas Happe et al. (1998, Developmental Psychology, 34, 358-362) showed better performances of elderly compared with young subjects in an advanced theory of mind (ToM) task, Mayor et al. (2002, British Journal of Psychology, 93, 465-485) and Sullivan and Ruffmann (2004, British Journal of Psychology, 95(Pt 1), 1-18) found an age-related decline. Former studies addressing the issue compared young to elderly subjects and did not investigate earlier changes in middle-aged adults. To shed light on changes in ToM skills along adulthood, the authors used the revised version of the "Reading the Mind in the Eyes Test" (Baron-Cohen et al., 2001, Journal of Child Psychology and Psychiatry, 42, 241-251) to compare four groups of people of different ages covering the whole span of adult life. The authors found aged-related decline in ToM skills as early as the fifth decade of life. Awareness of the age-related changes in adult mentalizing is important to differentiate normal aging effects from ToM impairments due to neuropsychiatric diseases.

2009 - Brain networks responsive to aversive visual stimuli in humans [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Duzzi, Davide; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

The neural mechanisms subserving recognition of noxious stimuli and empathy for pain appear to involve at least in part the corticalregions associated with the processing of pain affect. An important issue concerns the specificity of brain networks associated with observing and representing painful conditions, in comparison with other unpleasant stimuli. Recently, we found both similarities and differences between the brain patterns of activity related to the observation of noxious or disgusting stimuli delivered to one hand or foot. Overlap regions included the perigenual anterior cingulate (pACC), whose activity was related to the perceived unpleasantness. We aimed here atrevealing how pACC functional connectivity changes in relationship to the different experimental conditions, using a psychophysiological interaction model. Activity in pACC during the observation of painful stimuli was specifically and positively related to regions in the right hemisphere, including portions of the prefrontal, midcingulate and insular cortex. On the other hand, positive changes in pACC connectivity during the vision of disgusting stimuli were present in the right basal ganglia. These data suggest that pACC activity is part of different networks involved in the recognition of painful or disgusting stimuli.

2009 - Consciousness and Aphasia [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

Different language impairments allow us to investigate how much the use of language can influence the content of conscious awareness and therefore of thinking and reasoning. Pure anarthria (differently form mutism) and verbal short-term memory deficits are associated with an impairment of the effect of covert speech on the content of working memory. Dynamic aphasia impairs the processes involved in the transition between thinking and speaking. However, even the most severe agrammatic patients can retain reasoning about others ’ beliefs that according to some theories can only take place in explicit sentences of a natural language.Error monitoring is also impaired in many aphasic patients and in some of them is associated with complete lack of error awareness (anosognosia for aphasia).

2009 - Consciousness and Dementia: How the Brain Loses Its Self [Capitolo/Saggio]
P., Pietrini; E., Salmon; Nichelli, Paolo Frigio
abstract

Consciousness is based on the ability to rapidly integrate information and requires the optimal functioning of neural networks widely distributed between the thalami and the whole cortical mantle. Neurodegenerative processes that occur in dementing disorders, including Alzheimer’s disease, frontotemporal dementia and Lewy Body Disease, lead to a progressive disruption of the brain functional and anatomical connectivity that sustains complex mental activity in the human brain. Not only different dementia syndromes affect the brain in differentways but also patients with the same disease may show distinctive clinical features. By combining clinical, neuropsychological and functional brain imaging studies in selected patients, scientists are gaining new insights on the cerebral bases of conscious mental activity and of the neural events that make awareness of the surrounding world and of ourselves to dissolve.

2009 - Facial emotion recognition impairment in chronic temporal lobe epilepsy [Articolo su rivista]
Meletti, Stefano; Benuzzi, Francesca; G., Cantalupo; G., Rubboli; C. A., Tassinari; Nichelli, Paolo Frigio
abstract

PURPOSE: To evaluate facial emotion recognition (FER) in a cohort of 176 patients with chronic temporal lobe epilepsy (TLE). METHODS: FER was tested by matching facial expressions with the verbal labels for the following basic emotions: happiness, sadness, fear, disgust, and anger. Emotion recognition performances were analyzed in medial (n = 140) and lateral (n = 36) TLE groups. Fifty healthy subjects served as controls. The clinical and neuroradiologic variables potentially affecting the ability to recognize facial expressions were taken into account. RESULTS: The medial TLE (MTLE) group showed impaired FER (86% correct recognition) compared to both the lateral TLE patients (FER = 93.5%) and the controls (FER = 96.4%), with 42% of MTLE patients recording rates of FER that were lower [by at least 2 standard deviations (SDs)] than the control mean. The MTLE group was impaired compared to the healthy controls in the recognition of all basic facial expressions except happiness. The patients with bilateral MTLE were the most severely impaired, followed by the right and then the left MTLE patients. FER was not affected by type of lesion, number of antiepileptic drugs (AEDs), aura semiology, or gender. Conversely, the early onset of seizures/epilepsy was related to FER deficits. These deficits were already established in young adulthood, with no evidence of progression in older MTLE patients. CONCLUSION: These results on a large cohort of TLE patients demonstrate that emotion recognition deficits are common in MTLE patients and widespread across negative emotions. We confirm that early onset seizures with right or bilateral medial temporal dysfunction lead to severe deficits in recognizing facial expressions of emotions.

2009 - Impairment in Decoding Eye-Region Emotional Content in Mesial Temporal Lobe Epilepsy [Abstract in Rivista]
G., Cantalupo; Benuzzi, Francesca; G., Rubboli; C. A., Tassinari; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2009 - Parole ed emozioni: Come il significato delle parile si riflette nell’attività cerebrale [Capitolo/Saggio]
Benuzzi, Francesca; Tondelli, Manuela; Nichelli, Paolo Frigio
abstract

non disponibile

2009 - Time estimation in mild Alzheimer's disease patients [Articolo su rivista]
L., Caselli; L., Iaboli; Nichelli, Paolo Frigio
abstract

ABSTRACT: BACKGROUND: Time information processing relies on memory, which greatly supports the operations of hypothetical internal timekeepers. Scalar Expectancy Theory (SET) postulates the existence of a memory component that is functionally separated from an internal clock and other processing stages. SET has devised several experimental procedures to map these cognitive stages onto cerebral regions and neurotransmitter systems. One of these, the time bisection procedure, has provided support for a dissociation between the clock stage, controlled by dopaminergic systems, and the memory stage, mainly supported by cholinergic neuronal networks. This study aimed at linking the specific memory processes predicted by SET to brain mechanisms, by submitting time bisection tasks to patients with probable Alzheimer's disease (AD), that are known to present substantial degeneration of the fronto-temporal regions underpinning memory. METHODS: Twelve mild AD patients were required to make temporal judgments about intervals either ranging from 100 to 600 ms (short time bisection task) or from 1000 to 3000 ms (long time bisection task). Their performance was compared with that of a group of aged-matched control participants and a group of young control subjects. RESULTS: Long time bisection scores of AD patients were not significantly different from those of the two control groups. In contrast, AD patients showed increased variability (as indexed by increased WR values) in timing millisecond durations and a generalized inconsistency of responses over the same interval in both the short and long bisection tasks. A similar, though milder, decreased millisecond interval sensitivity was found for elderly subjects. CONCLUSION: The present results, that are consistent with those of previous timing studies in AD, are interpreted within the SET framework as not selectively dependent on working or reference memory disruptions but as possibly due to distortions in different components of the internal clock model. Moreover, the similarity between the timing patterns of elderly and AD participants raises the important issue of whether AD may be considered as part of the normal aging process, rather than a proper disease.

2008 - Absence status epilepticus as first manifestation of Hashimoto's encephalopathy | [Stato di male frontale a tipo "assenza" come sintomo di esordio nella encefalopatia di Hashimoto] [Articolo su rivista]
Monti, Giulia; Pugnaghi, Matteo; Tondelli, Manuela; A., Ariatti; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Hashimoto's Encephalopathy is an underecognized condition, life-threatening, but treatable, and with a fast clinical improvement after steroid therapy. The clinical manifestations are heterogeneous, so the diagnosis in often difficult, and necessarily a diagnosis of exclusion. Epileptic seizures are a frequent onset symptom of Hashimoto's encephalopathy. In medical literature are described case report of Hashimoto's encephalopathy manifested with partial seizures, generalized seizure, or absence. Moreover, there are described few case report about status epilepticus as the first clinical manifestation of Hashimoto's encephalopathy. We described here two cases in which two patients without history of epilepsy, presented absence status epilepticus associated with fluctuating levels of consciousness. Both patients had elevated TSH level and sierum antithyroid antibodies (anti-thyreoperoxydas antibodies and anti-thyreoglobulin antibodies). Neuroimaging, hematological tests, complete rheumatologic panel, tumor markers and cerebrospinal fluid (CSF) analysis were normal. We excluded vascular, metabolic, tumor, and toxic causes. Ictal EEG showed continuously generalized sharp and slow wave, more evident in frontal electrode. Clinically, the patients presented eye-lid mioclonus and absence status. The patient were unresponsive to antiepileptic drug therapy but responded to high intravenous steroid treatment. Screening of serum anti-thyroid antibodies for unexplained encephalopathy with absences is suggested, as early recognition and prompt steroid treatment may lead to a favorable prognosis.

2008 - Adult neuronal ceroid lipofuscinoses (Kufs disease): An atypical case with recurrent occipital status epilepticus | [Ceroido-lipofuscinosi dell'adulto (malattia di Kufs): Un caso atipico con stati di male occipitali ricorrenti] [Articolo su rivista]
Pugnaghi, Matteo; A., Zini; Monti, Giulia; A., Ariatti; A., Todeschini; Nichelli, Paolo Frigio; G., Cenacchi; Meletti, Stefano
abstract

Kufs disease is the rare, adult-onset form of the neuronal ceroid-lipofuscinoses, characterized by early-onset dementia, progressive myoclonic epilepsy, gait disturbances, cerebellar and extrapyramidal symptoms, due to intraneuronal/extraneuronal accumulation of lipopigments (ceroid and lipofuscin-like). We describe the clinical evolution of an atypical case clinically characterized by slow progressive dementia and occipital recurrent status epilepticus.

2008 - Apathy and disinhibition in frontotemporal dementia: Insights into their neural correlates. [Articolo su rivista]
Zamboni, Giovanna; E. D., Huey; F., Krueger; Nichelli, Paolo Frigio; J., Grafman
abstract

BACKGROUND: Aberrant social behavior is a defining symptom of frontotemporal dementia (FTD) and may eventually occur in all syndromes composing the FTD spectrum. Two main behavioral abnormalities have been described: apathy and disinhibition, but their neuroanatomical correlates remain underspecified. METHODS: Sixty-two patients with a clinical diagnosis of FTD participated in the study. Voxel-based morphometry of MRI data was performed to explore the association between gray matter loss and severity of the two behavioral profiles as measured by the Apathy and Disinhibition subscales of the Frontal Systems Behavior Scale. RESULTS: Compared with a group of controls, the FTD group showed extensive bilateral atrophy predominantly involving frontal and temporal lobes. Within the FTD group, the severity of apathy correlated with atrophy in the right dorsolateral prefrontal cortex. The severity of disinhibition correlated with atrophy in the right nucleus accumbens, right superior temporal sulcus, and right mediotemporal limbic structures. CONCLUSIONS: Prefrontal and temporal regions are differentially associated with apathy and disinhibition. Our results support the view that successful execution of complex social behaviors relies on the integration of social knowledge and executive functions, represented in the prefrontal cortex, and reward attribution and emotional processing, represented in mesolimbic structures.

2008 - Bold temporal dynamics in absence seizures: An EEG-fMRI coregistration study [Articolo su rivista]
Benuzzi, F.; Pugnaghi, M.; Farinelli, V.; Nichelli, P.; Meletti, S.
abstract

Recent studies have demonstrated BOLD signal changes related to interictal generalized spike-wave discharge discharges in idiopathic generalized epilepsy (IGE) describing a cortical-subcortical network. Our objective is to describe BOLD dynamics and its temporal variations during absence seizures in patients with IGE. Method: We studied two patients with IGE and Juvenile Absence Epilepsy. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system. Functional data were acquired with a 3T Philips Achieva MR system. Event-related analysis was performed using absence seizures as regressors convolved with seven standard hemodynamic response function (HRF) starting at: -9, -6, -3 second before EEG onset of absence seizures, time 0 (onset),and +3, +6, +9 second after it. Results: Temporal analysis showed pre-ictal activations in frontal and parieto-occipital cortex. At seizure onset, activations were evident in thalamus, basal ganglia and mesial temporal regions. Deactivations were observed in precuneus from 6 sec before to 9 sec after the seizure onset, and in brainstem, caudate nuclei, anterior cingulate until 6 sec after it. Conclusion: Temporal analysis of absence seizures showed pre-ictal involvement of cortical regions (frontal cortex and precuneus). Then we observed an extended cortical-subcortical network including thalamus,basal ganglia, temporal mesial regions and brainstem. The involvement of these regions started at seizure onset and persisted many seconds after its end.

2008 - Bold temporal dynamics in absence seizures: An EEG-fMRI coregistration study | [Dinamica temporale del segnale bold in corso di crisi di assenza: Uno studio di co-registrazione EEG-fMRI] [Articolo su rivista]
Benuzzi, Francesca; Pugnaghi, Matteo; Farinelli, Valentina; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Recent studies have demonstrated BOLD signal changes related to interictal generalized spike-wave discharge discharges in idiopathic generalized epilepsy (IGE) describing a cortical-subcortical network. Our objective is to describe BOLD dynamics and its temporal variations during absence seizures in patients with IGE. Method: We studied two patients with IGE and Juvenile Absence Epilepsy. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system. Functional data were acquired with a 3T Philips Achieva MR system. Event-related analysis was performed using absence seizures as regressors convolved with seven standard hemodynamic response function (HRF) starting at: -9, -6, -3 second before EEG onset of absence seizures, time 0 (onset),and +3, +6, +9 second after it. Results: Temporal analysis showed pre-ictal activations in frontal and parieto-occipital cortex. At seizure onset, activations were evident in thalamus, basal ganglia and mesial temporal regions. Deactivations were observed in precuneus from 6 sec before to 9 sec after the seizure onset, and in brainstem, caudate nuclei, anterior cingulate until 6 sec after it. Conclusion: Temporal analysis of absence seizures showed pre-ictal involvement of cortical regions (frontal cortex and precuneus). Then we observed an extended cortical-subcortical network including thalamus,basal ganglia, temporal mesial regions and brainstem. The involvement of these regions started at seizure onset and persisted many seconds after its end.

2008 - Characterizationof a focal vascular lesionaffecting entorhinalcortex-CA3connections after statusepilepticus [Abstract in Rivista]
Biagini, Giuseppe; Longo, Daniela; Baldelli, Enrica; Contri, Miranda; Nichelli, Paolo Frigio; U., Guerrini; L., Sironi; P., Gelosa; G., Bertazzoni; M., Avoli
abstract

Pilocarpine mimics temporal lobeepilepsy by inducing SE associatedwith damage in hippocampal andextrahippocampal areas. We havecharacterized a vascular lesion thatdestroys the perforant path (PP) inCA3 after SE. This lesion (white arrows,Figure 1) was evident withmagnetic resonance imaging 1 day aftera SE lasting for 120 min and its appearancewas delayed by limiting SEto 60 or 30 min. Rats exposed to SEfor 30 min developed the lesion unlesssubsequently treated with diazepam(20 mg/kg s.c. for 3 days), whichprotected 50% of the animals. Antibodiesfor astrocytes (GFAP), dendrites(MAP2) and PPnerve terminals(mGluR2/3), showed areas of immunoreactivityloss in which we localizedincreased staining for laminin, inthe basement membrane of vessels.This lesion was uncommon in young(3-week-old) rats. The latent periodfor seizure appearance was similar inadult rats exposed to SE only or to SEfollowed by neuroprotection with diazepam;however, the frequency ofspontaneous seizures was significantlylower (p < 0.01) in the neuroprotectedgroup. Moreover, spontaneousseizures were delayed in youngrats (p < 0.01) exposed to 60 min SEcompared to adults experiencing asimilar SE. To investigate the role ofdamaged CA3 in seizure activity, were-induced SE in adult and young epilepticrats. Using FosB/FosB markers,we found induction of FosB/FosB immunopositivity in CA3neurons of young but not in adult rats.These experiments reveal that SE canproduce a focal lesion in the PP, whichaffects the role of the hippocampus inepileptic rats.

2008 - Clinica e neuropsicologia del deterioramento cognitivo [Capitolo/Saggio]
Nichelli, Paolo Frigio; Zamboni, Giovanna
abstract

non disponibile

2008 - Does it look painful or disgusting? Ask your parietal and cingulate cortex [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Duzzi, Davide; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

Looking at still images of body parts in situations that are likely to cause pain has been shown to be associated with activation in some brain areas involved in pain processing. Because pain involves both sensory components and negative affect, it is of interest to explore whether the visually evoked representations of pain and of other negative emotions overlap. By means of event-related functional magnetic resonance imaging, here we compare the brain areas recruited, in female volunteers, by the observation of painful, disgusting, or neutral stimuli delivered to one hand or foot. Several cortical foci were activated by the observation of both painful and disgusting video clips, including portions of the medial prefrontal cortex, anterior, mid-, and posterior cingulate cortex, left posterior insula, and right parietal operculum. Signal changes in perigenual cingulate and left anterior insula were linearly related to the perceived unpleasantness, when the individual differences in susceptibility to aversive stimuli were taken into account. Painful scenes selectively induced activation of left parietal foci, including the parietal operculum, the postcentral gyrus, and adjacent portions of the posterior parietal cortex. In contrast, brain foci specific for disgusting scenes were found in the posterior cingulate cortex. These data show both similarities and differences between the brain patterns of activity related to the observation of noxious or disgusting stimuli. Namely, the parietal cortex appears to be particularly involved in the recognition of noxious environmental stimuli, suggesting that areas involved in sensory aspects of pain are specifically triggered by observing noxious events.

2008 - EEG-fMRI coregistration of absence seizures in patients with juvenile absence epilepsy | [Coregistrazione EEG-fMRI delle crisi di assenza in pazienti con juvenile absence epilepsy] [Articolo su rivista]
Pugnaghi, Matteo; Benuzzi, Francesca; Monti, Giulia; Farinelli, Valentina; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Simultaneous coregistration of EEG and fMRI (EEG-fMRI) is a new methodology which enables to identify changes in cerebral blood oxygenation level-dependent (BOLD) signal related to specific EEG events. Our objective is to describe BOLD dynamics during absence seizures in patients with Juvenile Absence Epilepsy (JAE). Methods: we studied two patients with JAE, without antiepileptic drug at the time of scanning. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system. Functional data were acquired with a 3T Philips Achieva system. Event-related analysis was performed on functional data with SPM2 software. Results: seven and 13 absence seizures were recorded in the two patients. BOLD temporal dynamics showed activations in thalamus, medial temporal regions and pre-frontal cortex. Furthermore we observed deactivations in brainstem, caudate nuclei and widespread cortical regions, including precuneus, posterior parietal areas and pre-frontal cortex. Conclusion: We found cortical-subcortical BOLD network mostly overlapping of what previously described in GSWD of IGE. In addition we observed BOLD variations in brainstem and medial temporal regions not previously reported. We speculate that these data could be in relation to occurrence of absence seizures rather than GSWD and/or to the presence of complex absences with post-ictal oral automatisms.

2008 - Early-onset dementia with prolonged occipital seizures: an atypical case of Kufs disease [Articolo su rivista]
A., Zini; G., Cenacchi; Nichelli, Paolo Frigio; E., Zunarelli; A., Todeschini; Meletti, Stefano
abstract

OBJECTIVE: Kufs disease is the adult-onset form of neuronal ceroid lipofuscinosis (NCL). Its two clinical phenotypes are type A (progressive myoclonus epilepsy with dementia) and type B (behavioral abnormalities and dementia, associated with pyramidal and extrapyramidal signs). METHODS: We describe the clinical evolution of an atypical case characterized by progressive dementia and focal occipital seizures. RESULTS: A healthy 37-year-old woman began showing memory deficits and behavioral disturbances (apathy, lack of inhibitions, untidiness). After 4 years, she developed rare clusters of tonic-clonic seizures, as well as focal seizures originating from the temporo-occipital regions, clinically associated with visual hallucinations, wandering, and agitation. When she was 44 years old, neuropsychological assessment revealed severe frontotemporal dementia. MRI showed cortical atrophy and, on T2-weighted images, hypointensity of the basal ganglia, and hyperintensity and reduction of the deep white matter. On the basis of these findings, a diagnosis of Kufs disease was hypothesized. A skin biopsy was negative, but electron microscopy examination of a right frontal lobe brain biopsy revealed the presence of typical storage material (fingerprint inclusions). The patient never developed myoclonus or extrapyramidal signs. DISCUSSION: Kufs disease is difficult to diagnose on account of its heterogeneous clinical pattern and pathologic features, and the lack of a specific genetic locus alteration. The neuropsychological pattern and MRI findings observed in patients with early-onset frontotemporal dementia and seizure disorder suggest that Kufs disease should be considered in their differential diagnosis. Extracerebral biopsy can be nondiagnostic, and when alternative diagnoses have been ruled out, cerebral biopsy should be considered.

2008 - Neural substrates for observing and imagining non-object-directed actions [Articolo su rivista]
Lui, Fausta; G., Buccino; Duzzi, Davide; Benuzzi, Francesca; G., Crisi; Baraldi, Patrizia; Nichelli, Paolo Frigio; Porro, Carlo Adolfo; G., Rizzolatti
abstract

The present fMRI study was aimed at assessing the cortical areas active when individuals observe non-object-directed actions (mimed, symbolic, and meaningless), and when they imagine performing those same actions. fMRI signal increases in common between action observation and motor imagery were found in the premotor cortex and in a large region of the inferior parietal lobule. While the premotor cortex activation overlapped that previously found during the observation and imagination of object-directed actions, in the parietal lobe the signal increase was not restricted to the intraparietal sulcus region, known to be active during the observation and imagination of object-directed actions, but extended into the supramarginal and angular gyri. When contrasting motor imagery with the observation of non-object-directed actions, signal increases were found in the mesial frontal and cingulate cortices, the supramarginal gyrus, and the inferior frontal gyrus. The opposite contrast showed activation virtually limited to visual areas. In conclusion, the present data define the common circuit for observing and imagining non-object-directed actions. In addition, they show that the representation of non-object-directed actions include parietal regions not found to be involved in coding object-directed actions.

2008 - PROMINENT BRAINSTEM, THALAMIC AND AMYGDALA INVOLVEMENT IN ABSENCE SEIZURES WITH PERIORAL AUTOMATISMS AS REVEALED BY EEG-fMRI [Abstract in Rivista]
Pugnaghi, Matteo; Benuzzi, Francesca; Monti, Giulia; Farinelli, Valentina; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2008 - RECOGNITION OF BASIC AND SOCIAL EMOTIONS THROUGH FACE AND VOICE IN PATIENTS WITH MEDIAL TEMPORAL LOBE EPILEPSY [Abstract in Rivista]
Monti, Giulia; Benuzzi, Francesca; Pugnaghi, Matteo; M., Molinari; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

2008 - Recognition of emotions from visual and prosodic cues in Parkinson's disease [Articolo su rivista]
Benuzzi, Francesca; Nichelli, Paolo Frigio; Ariatti, Alessandra
abstract

OBJECTIVE: To assess whether Parkinson Disease (PD) patients are impaired at perceiving emotions from facial and prosodic cues and whether any putative defective performance concerns recognition of a particular emotion. BACKGROUND: Braak et al. [1] demonstrated that in different stages PD pathology involves the nigrostriatal system, the amygdala, and the insular cortex. Discrete brain lesions to these structures can cause selective deficits in recognising facial and prosodic stimuli expressing particular emotions. However, the investigation of facial and prosodic emotional processing in PD patients has lead to conflicting results. MATERIALS AND METHODS: We compared 27 cognitively unimpaired PD patients with control subjects by means of the Facial Emotion Recognition Battery and the Emotional Prosody Recognition Battery. RESULTS: PD patients were impaired in recognising, selecting, and matching facial affects. In particular, the Facial Emotion Recognition Battery demonstrated a severe impairment in recognising sad and fearful faces. In the Emotional Prosody Recognition Battery PD patients demonstrated a diffuse impairment, including the recognition of emotional and propositional prosody. CONCLUSIONS: Face emotion processing is impaired in PD patients, with a disproportionate deficit involving fear and sadness. The pattern of face expression processing impairment in PD patients might depend on the regional distribution of the pathology. The widespread involvement of both emotional and propositional prosodic processing parallels the aprosodic characteristics of Parkinsonian speech production.

2008 - Social cognition in patients with temporal lobe epilepsy [Articolo su rivista]
Monti, G.; Benuzzi, F.; Pugnaghi, M.; Molinari, M.; Nichelli, P.; Meletti, S.
abstract

Several studies demonstrated the critical role on processing emotional stimuli of mesial temporal lobe structures, which is the common pathologic substrate of Temporal Lobe Epilepsy associated with Mesial Temporal Sclerosis (TLE-MTS). The present study evaluated the emotional processing in TLE-MTS requiring patients to recognise facial and prosodic expressions of both basic and social emotions. Subjects: 11 patients with TLE-MTS. 12 patients with Temporal Lobe Epilepsy associated with other etiology (TLE-les) and 30 normal controls were evaluated. TLE-MTS patients were impaired in recognition all negative basic emotions (fear, sadness, angry, disgust) both from facial and prosodic expressions. They also showed a generalized deficit in social emotions recognitions whereas TLE-les patients were impaired in recognition of one specific social emotion (guilty). Our findings could also account for difficulties in social interactions often found in patients with mesial temporal lobe epilepsy.

2008 - Social cognition in patients with temporal lobe epilepsy | [La cognizione sociale nei pazienti con epilessia del lobo temporale] [Articolo su rivista]
Monti, Giulia; Benuzzi, Francesca; Pugnaghi, Matteo; M., Molinari; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Several studies demonstrated the critical role on processing emotional stimuli of mesial temporal lobe structures, which is the common pathologic substrate of Temporal Lobe Epilepsy associated with Mesial Temporal Sclerosis (TLE-MTS). The present study evaluated the emotional processing in TLE-MTS requiring patients to recognise facial and prosodic expressions of both basic and social emotions. Subjects: 11 patients with TLE-MTS. 12 patients with Temporal Lobe Epilepsy associated with other etiology (TLE-les) and 30 normal controls were evaluated. TLE-MTS patients were impaired in recognition all negative basic emotions (fear, sadness, angry, disgust) both from facial and prosodic expressions. They also showed a generalized deficit in social emotions recognitions whereas TLE-les patients were impaired in recognition of one specific social emotion (guilty). Our findings could also account for difficulties in social interactions often found in patients with mesial temporal lobe epilepsy.

2008 - Temporal epilepsy and social cognition in a patient with Turner syndrome [Articolo su rivista]
Tondelli, M.; Benuzzi, F.; Molinari, M. A.; Ariatti, A.; Pugnaghi, M.; Monti, G.; Nichelli, P.; Meletti, S.
abstract

Turner syndrome (TS) is a genetic disorder arising from X-monosomy or mosaicism. This genetic condition is associated with specific cognitive deficits and variations in brain volumes, especially in temporal lobes. Epilepsy is unusual in TS and only few cases have been reported, frequently associated with cerebral development abnormalities. In our report, we described the case of focal left temporal epilepsy without cerebral malformations in a woman with TS mosaicism.

2008 - Temporal epilepsy and social cognition in a patient with Turner syndrome | [Epilessia temporale e cognizione sociale in una paziente con sindrome di Turner] [Articolo su rivista]
Tondelli, Manuela; Benuzzi, Francesca; M. A., Molinari; A., Ariatti; Pugnaghi, Matteo; Monti, Giulia; Nichelli, Paolo Frigio; Meletti, Stefano
abstract

Turner syndrome (TS) is a genetic disorder arising from X-monosomy or mosaicism. This genetic condition is associated with specific cognitive deficits and variations in brain volumes, especially in temporal lobes. Epilepsy is unusual in TS and only few cases have been reported, frequently associated with cerebral development abnormalities. In our report, we described the case of focal left temporal epilepsy without cerebral malformations in a woman with TS mosaicism.

2008 - Temporal lobe epilepsy and social cognition assessment in a case of Urbach-Wiethe disease | [Epilessia temporale e cognizione sociale in una paziente affetta da malattia di Urbach-Wiethe] [Articolo su rivista]
G., Cantalupo; Meletti, Stefano; Benuzzi, Francesca; R., Michelucci; A. F., Marliani; S., Silipo; Nichelli, Paolo Frigio; G., Rubboli
abstract

We describe anatomo-electro-clinical features of temporal lobe epilepsy and social cognition skills in a 38 years old woman affected by Urbach-Wiethe disease. Patient's clinical history had typical features beginning in early infancy with low-pitched cry and hoarseness, due to vocal cords thickening, associated with cutaneous scar-like lesions and moniliform blepharosis. At age 13 genetic diagnosis was obtained finding mutation in extracellular matrix protein 1 gene. Since 8 years of age temporal-lobe seizures occurred. The patient underwent long-term video-EEG showing interictal slight bi-temporal theta rhythm and ictal EEG revealing rhythmic theta sequence on right temporal region during a subjective episode, without impairment of consciousness. Neuroimaging demonstrated bilateral comma-shaped calcifications involving amygdala, with mild abnormal signal in surrounding parenchyma. Social cognition assessment revealed only moderate deficit in recognition of facial expression of fear. Characteristic selective bilateral amygdala calcifications, frequently observed in Urbach-Wiethe disease, served as a model to prove the critical role of human amygdala in facial emotion recognition. Moderate and selective fear recognition deficit in our patient confirms the neuropsychological variability observed in these patients, probably related to damage timing.

2008 - Video-EEG in functional MRI | [Video-EEG-fMRI] [Articolo su rivista]
Farinelli, Valentina; Benuzzi, Francesca; Meletti, Stefano; Pugnaghi, Matteo; Nichelli, Paolo Frigio; M., Serafini
abstract

Combined EEG-fMRI is a methodology which enables to identify regional blood flow variations (BOLD contrast) associated with specific EEG events. We aimed to develop a technique allowing to acquire video images during EEG-fMRI recordings. We used a magnet compatible EEG recordings system (Micromed, S.P.A, Italy) designed to minimize interferences due to magnetic fields. In order to record video images we used a shielded video-camera with a flexible arm secured to the Radio Frequency coil. Video signals were synchronized with neurophysiological data in order to achieve a real video-EEG recording. Although some decay of the EEG signal due to magnetic field artefacts,we obtained satisfactory results allowing a real video-EEG recording with video monitoring of the patient's face. Integration of EEG-fMRI data with video images permit to widen our knowledge of clinical events which may appear during the EEG recording.

2007 - I disturbi emozionali associati a malattie neurologiche [Capitolo/Saggio]
Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

non disponibile

2007 - Processing the socially relevant parts of faces [Articolo su rivista]
Benuzzi, Francesca; Pugnaghi, Matteo; Meletti, Stefano; Lui, Fausta; M., Serafini; Baraldi, Patrizia; Nichelli, Paolo Frigio
abstract

Faces are processed by a distributed neural system in the visual as well as in the non-visual cortex [the “core” and the “extended” systems, J.V. Haxby, E.A. Hoffman, M.I. Gobbini, The distributed human neural system for face perception, Trends Cogn. Sci. 4 (2000) 223–233]. Yet, the functions of the different brain regions included in the face processing system are far from clear. On the basis of the case study of a patient unable to recognize fearful faces, Adolphs et al. [R. Adolphs, F. Gosselin, T.W. Buchanan, D. Tranel, P. Schyns, A.R. Damasio, A mechanism for impaired fear recognition after amygdala damage, Nature 433 (2005) 68–72] suggested that the amygdala might play a role in orienting attention towards the eyes, i.e. towards the region of face conveying most information about fear. In a functional magnetic resonance (fMRI) study comparing patterns of activation during observation of whole faces and parts of faces displaying neutral expressions, we evaluated the neural systems for face processing when only partial information is provided, as well as those involved in processing two socially relevant facial areas (the eyes and the mouth).Twenty-four subjects were asked to perform a gender decision task on pictures showing whole faces, upper faces (eyes and eyebrows), and lower faces (mouth). Our results showed that the amygdala was activated more in response to the whole faces than to parts of faces, indicating that the amygdala is involved in orienting attention toward eye and mouth. Processing of parts of faces in isolation was found to activate other regions within both the “core” and the “extended” systems, as well as structures outside this network, thus suggesting that these structures are involved in building up the representation of the whole face from its parts.

2007 - Progressive supranuclear gaze palsy without parkinsonism: a case of neuro-Whipple [Articolo su rivista]
Magherini, A; Pentore, R; Grandi, M; Leone, Me; Nichelli, Paolo Frigio
abstract

We report the case of a 69-year-old man with a 7-month history of severe progressive supranuclear gaze palsy associated with mild cognitive decline and sleep disturbances, but not parkinsonism. After a period spent consulting a range of different specialists, the appearance of brachial myoclonus prompted his referral to a movement disorders specialist. Duodenum biopsy confirmed the suspicion of neuro-Whipple disease. Antibiotic therapy was started but the delay in the diagnosis proved fatal to this patient. This noteworthy case shows unusual neurological features of a rare but treatable disease, often misdiagnosed as progressive supranuclear palsy

2006 - Amyotrophic lateral sclerosis: Prognostic indicators of survival [Articolo su rivista]
Mandrioli, Jessica; Faglioni, Pietro; Nichelli, Paolo Frigio; P., Sola
abstract

Amyotrophic lateral sclerosis (ALS) has a fatal outcome in about three years, but survival is known to vary considerably, making it difficult to predict disease duration in individual cases. The aim of this study was to investigate possible early prognostic factors of ALS survival. We included 123 probable or definite cases of ALS, with disease onset between 1989 and 1998, and with a follow-up of at least one year. Survival functions were obtained using both the Kaplan-Meier and the actuarial methods. Subgroups, formed on the basis of gender, area of residence, work, and age at and site of onset, were compared using the logrank test and Cox's proportional hazards method (survival functions), and applying the Grizzle, Starmer, Koch (1969), and Koch, Johnson, Tolley (1972) methods (one-year survival probability trends). The survival curves dipped sharply in the first three years, followed by a flattening trend, with 50% of patients dying within 2.5 years, and 89% over seven years. The clinical form with lower limb onset was associated with longer survival than the upper limb onset and bulbar forms (median survival: 39, 27, and 25 months, respectively). Survival was also affected by age at onset (median survival: 34, 27, and 23 months for onset < 60, 60-75, and > 75 years, respectively), area of residence (median survival: 24 months in mountainous areas, 32 elsewhere), and type of work (median survival: 25 months in agricultural workers, 33.5 in others). Gender did not influence survival, whereas percutaneous endoscopic gastrostomy placement and invasive ventilation did. The estimation of individual ALS survival is important to allow the patient to plan for his future and to make optimal use of medical and community resources. Although age at and site of onset, area of residence, and agricultural work were found to influence survival, there remains an unexplained heterogeneous progression of the disease, suggesting the influence of other, as yet unknown, prognostic factors. The identification of a definite set of prognostic factors may allow physicians to make more reliable survival predictions at diagnosis.

2006 - Bilateral posterior medullary and cervical stroke: a case report [Articolo su rivista]
Mandrioli, Jessica; Zini, Andrea; F., Cavalleri; Nichelli, Paolo Frigio; Panzetti, Patrizia
abstract

Spinal strokes are often localised in the anterior spinal artery territory, whereas an involvement of the posterior spinal arteries (PSA) is uncommon, and usually unilateral. Bilateral PSA stroke is exceptional. A 70-year-old woman, after a mild head trauma, presented with cervical pain, left hypoaesthesia and sensitive ataxia, which then extended to the right hemibody, including face. A Doppler ultrasound showed an only systolic flow signal in the left vertebral artery (VA). MR showed a bilateral infarction extending from the posterior medulla oblongata to C4 and a left hypoplasic VA with lack of visualisation of the V3 segment. This case was peculiar, implying a bilateral stroke in the PSA territory, possibly related to a left VA dissection, and in the presence of a dominant PSA, originating from the hypoplasic VA and of hyposupply of posterior radiculomedullary arteries and anastomoses.

2006 - Do flavan-3-ols from green tea reach the human brain? [Articolo su rivista]
Zini, Andrea; D., Del Rio; A. J., Stewart; Mandrioli, Jessica; E., Merelli; P., Sola; Nichelli, Paolo Frigio; M., Serafini; F., Brighenti; C. A., Edwards; A., Crozier
abstract

Following acute ingestion of green tea by six human subjects, HPLC-MS 2 analysis revealed that flavan-3-ol methyl, glucuronide and sulfate metabolites appeared in the bloodstream but did not pass through the blood-cerebrospinal fluid barrier. These observations emphasize the discrepancies between in vitro and in vivo evidence on the neuroprotective role of these compounds. If, as has been proposed, green tea exerts neuroprotective effects, this finding indicates that the active components are not flavan-3-ols or their metabolites. Alternatively, a systemic action may be hypothesised whereby dietary flavan-3-ols up-regulate antioxidant defences and/or reduce inflammation, the benefit of which may be effective throughout the body.

2006 - Humor comprehension and appreciation: an fMRI study [Articolo su rivista]
Bartolo, Angela; Benuzzi, Francesca; L., Nocetti; Baraldi, Patrizia; Nichelli, Paolo Frigio
abstract

Humor is a unique ability in human beings. Suls [A two-stage model for the appreciation of jokes and cartoons. In P. E. Goldstein & J. H. McGhee (Eds.), The psychology of humour. Theoretical perspectives and empirical issues. New York: Academic Press, 1972, pp. 81-100] proposed a two-stage model of humor: detection and resolution of incongruity. Incongruity is generated when a prediction is not confirmed in the final part of a story. To comprehend humor, it is necessary to revisit the story, transforming an incongruous situation into a funny, congruous one. Patient and neuroimaging studies carried out until now lead to different outcomes. In particular, patient studies found that right brain-lesion patients have difficulties in humor comprehension, whereas neuroimaging studies suggested a major involvement of the left hemisphere in both humor detection and comprehension. To prevent activation of the left hemisphere due to language processing, we devised a nonverbal task comprising cartoon pairs. our findings demonstrate activation of both the left and the right hemispheres when comparing funny versus nonfunny cartoons. In particular, we found activation of the right inferior frontal gyrus (BA 47), the left superior temporal gyrus (BA 38), the left middle temporal gyrus (BA 21), and the left cerebellum. These areas were also activated in a nonverbal task exploring attribution of intention [Brunet, E., Sarfati, Y., Hardy-Bayle, M. C., & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage, 11, 157-166, 2000]. We hypothesize that the resolution of incongruity might occur through a process of intention attribution. We also asked subjects to rate the funniness of each cartoon pair. A parametric analysis showed that the left amygdala was activated in relation to subjective amusement. We hypothesize that the amygdala plays a key role in giving humor an emotional dimension.

2006 - Isolated Hypoglossal nerve palsy due to amyloid cervical arthropathy in long term hemodialysis [Articolo su rivista]
Mandrioli, J; Zini, A; Cavalleri, F; Vandelli, L; Nichelli, Paolo Frigio; Colombo, A.
abstract

nd

2006 - Left ipsilesional neglect for visual imagery: A mental image generation impairment? [Articolo su rivista]
Cocchini, G; Bartolo, A; Nichelli, Paolo Frigio
abstract

In this article, we describe a patient, CN, with unilateral left posterior brain damage, who shows a rare occurrence of left ipsilesional neglect limited to mental representations. CN's clinical pattern is consistent with the hypothesis that different mechanisms underlie perceptual and representational neglect. We also discuss an interpretation of representational neglect based on the different involvement of the two hemispheres in visual imagery processes. In particular, left brain lesions do not present the typical strong contralesional bias and may lead to an impairment of mental generation of either side of the image, depending on pre-morbid and methodological factors.

2006 - List effect in apraxia assessment [Articolo su rivista]
Cubelli, R; Bartolo, Angela; Nichelli, Paolo Frigio; Della Sala, S.
abstract

Imitation tests encompassing intermingled meaningful and meaningless items are normally used to assess ideomotor apraxia, implicitly assuming that they would test the lexical and the non-lexical route, respectively. However, these mixed lists might induce a list composition effect similar to that found in word recognition studies where familiar material can be processed via the non-lexical route. This hypothesis was put to test by examining praxis skills of 23 left-hemisphere damaged patients using the same gestures in two formats: pure and mixed lists (i.e., meaningless or meaningful gestures administered separately or intermingled, respectively). Results showed that patients performed better on the imitation task when pure lists were used. Moreover, asymmetries of performance were observed. Patient SL scored better in the imitation of meaningful gestures in the pure list than in the mixed list condition. Patient CA performed poorly in the imitation of meaningless gestures only in the mixed list condition. Dissociations observed in imitation tasks could be biased by the use of mixed lists. Also pure lists should be used for the diagnosis of imitation deficits in apraxia. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

2006 - Total antioxidant capacity of cerebrospinal fluid is decreased in patients with motor neuron disease [Articolo su rivista]
Mandrioli, J; Del Rio, D; Zini, A; Nichelli, Paolo Frigio; Merelli, E; Beltrami, D; Cesari, C; Pellegrini, N; Brighenti, F; Sola, P.
abstract

Oxidative stress has been associated with motor neuron disease (MND). The human body has several antioxidant defense systems to repair the damage caused by oxidative stress. The activity of these systems is thought to be reduced in neurodegenerative diseases, which may increase the level of oxidative damage and be a contributing factor to motor neuron death. In the present study, we compared the total antioxidant capacity (TAC) of human serum and cerebrospinal fluid (CSF) of MND patients with that of a control group including patients with migraine, tension headache and psychiatric disorders. Within-subject serum and CSF TAC were strongly correlated (r = 0.639; p = 0.000), and CSF TAC was significantly lower in MND patients as compared to controls after adjustment for known influencing factors (112.7 mu mol Fe/L +/- 11.7 versus 135.2 mu mol Fe/L +/- 19.7; p = 0.012). No differences in serum or CSF TAC were observed among the clinical forms of MND considered in this work. In conclusion, the CSF TAC was strongly correlated with serum TAC, and a decrease in CSF TAC was demonstrated in MND patients compared to controls that was not independent from serum antioxidants, this translating in a systemic (but prevailing in the CNS) oxidative damage in this pathology.

2005 - "Seeing oneself": A case of autoscopy [Articolo su rivista]
Zamboni, Giovanna; C., Budriesi; Nichelli, Paolo Frigio
abstract

Autoscopy is the experience of seeing an image of one's body in external space. We describe the case of a patient who reported longstanding autoscopic hallucinations following post-eclamptic brain damage. The MR scan demonstrated damage involving the occipital cortex and the basal ganglia bilaterally. We hypothesize that the image was the result of aberrant plasticity mechanisms involving cortical areas that play a central role in high-order body or representation of oneself.

2005 - A step forward an integrated network for Neuropsychology research: Highlights from the ‘First Congress of the European Neurosychological Societies’. Modena, (Italy),18th-20th April 2004. [Recensione in Rivista]
Nichelli, Paolo Frigio
abstract

2005 - Grammatical gender in the brain: Evidence from an fMRI study on Italian [Articolo su rivista]
Padovani, Roberto; CALANDRA BUONAURA, Giovanna; Cacciari, Cristina; Benuzzi, Francesca; Nichelli, Paolo Frigio
abstract

The grammatical gender of a word is a lexical-syntactic property determining agreement among different sentence parts. Recent fMRI investigations identified the areas involved in the retrieval of grammatical gender near the left Broca´s area providing further evidence to confirm the preeminent syntactic role of this area. However, these studies employed categorical designs based on the controversial methodology of the cognitive subtraction of neural activations related to different tasks. In the present study we identified the neural substrates of grammatical gender assignment using an fMRI parametric study. Participants decided the grammatical gender of visually presented Italian words whose gender-to-ending regularity varied. The results showed activation in left and right fronto-temporal areas suggesting an interplay of both hemispheres in the processing of grammatical gender.

2005 - Recognition of facial expressions of emotions in MTLE: Analysis of 122 consecutive patients [Abstract in Rivista]
Meletti, Stefano; Benuzzi, Francesca; M., Alessandria; G., Calandra Buonaura; G., Rubboli; M., Vedovello; P., Tinuper; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

2005 - Role of visuospatial cognition assessment in the diagnosis and research of atypical parkinsonian disorders [Capitolo/Saggio]
Nichelli, Paolo Frigio; Magherini, Anna
abstract

Visuospatial abilities play a pivotal role in our daily living. Indeed, our survival depends, to a great extent, on our ability to navigate sensory space. This means our ability to use spatial maps dependent on visual, tactile, and auditory information to form and guide motor programs. Visuospatial abilities are complex brain operations requiring integration of occipital, parietal, and frontal lobe function, as well as the contribution of subcortical structures. Consequently, it is not surprising that visuospatial skills are often impaired in diseases with movement disorders—an impairment that depends both on the type and on the stage of the disease in question. Investigating visuospatial skills is helpful not only for differentiating among various diseases with movement disorders, but also for analyzing the source of patients’ everyday life impairment, as this can, in turn, generate useful pointers for the development of remedial strategies. Also, in the detailed analysis of visuospatial performance in patients with movement disorders,particular care must be taken to separate motor from cognitive components. In the devising of neuropsychological tools that can help us to gain a new insight into cortical and subcortical contributions to these activities, this represents a constant challenge. The aim of this chapter is to review the contribution of visuospatial assessment in the differential diagnosis of movement disorders. After presenting a classification of visuospatial skills, we discuss the evidence of visuospatial dysfunction in Parkinson’s disease (PD) and in the various atypical parkinsonian disorders. We then advance our own proposal for visuospatial assessment in this group of patients.

2005 - Temporal Production and Visuo-Spatial Processing [Articolo su rivista]
Benuzzi, Francesca; Basso, Gianpaolo; Nichelli, Paolo Frigio
abstract

Current models of prospective timing hypothesize that estimated duration is influenced either by the attentional load or by the short-term memory requirements of a concurrent nontemporal task. In the present study, we addressed this issue with four dual-task experiments. In Exp. 1, the effect of memory load on both reaction time and temporal production Was proportional to the number of items of a visuospatial pattern to hold in memory. In Exps. 2, 3, and 4, a temporal production task was combined with two visual search tasks involving either pre-attentive or attentional processing. Visual tasks interfered with temporal production: produced intervals were lengthened proportionally to the display size. In contrast, reaction times increased with display size only when a serial, effortful search was required. It appears that memory and perceptual set size, rather than nonspecific attentional or short-term load, can influence prospective timing.

2005 - The Frontal Assessment Battery (FAB): Normative values in an Italian population sample [Articolo su rivista]
I., Appollonio; M., Leone; V., Isella; F., Piamarta; T., Consoli; Ml, Villa; E., Forapani; A., Russo; Nichelli, Paolo Frigio
abstract

The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six-subtest battery for the bedside screening of a global executive dysfunction; although recently devised, it is already extensively used thanks to its ease of administration and claimed sensitivity. The aim of the present study was to derive Italian normative values from a sample of 364 control subjects (215 women and 149 men) of different ages (mean: 57.4 +/- 17.9 years; range: 20-94 years) and educational level (mean: 10.4 +/- 4.3 years.; range: 1-17 years); the Mini Mental State Examination (MMSE) was concurrently administered. Multiple linear regression analysis revealed significant effects for age and education whereas gender was not significant; thus, from the derived linear equation, a correction grid for FAB raw scores was built. Based on nonparametric techniques, inferential cut-off scores were subsequently determined and equivalent scores (ES) computed. Test-restest and inter-rater reliabilities were both satisfactory. Interestingly, MMSE was significantly correlated with FAB raw scores, whereas adjusted scores were not. The present data may improve the accuracy in the use of the FAB both for clinical and research purposes.

2004 - Disruption of a neural network subserving facial expression processing in right mesial temporal lobe epilepsy [Abstract in Rivista]
Meletti, Stefano; Benuzzi, Francesca; G., Calandra Buonaura; G., Rubboli; M., Serafin; Lui, Fausta; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

2004 - Functional and Neural Mechanisms of Interval Timing [Recensione in Rivista]
Nichelli, Paolo Frigio
abstract

2004 - Impaired fear processing in right mesial temporal sclerosis: a fMRI study [Articolo su rivista]
Benuzzi, Francesca; Meletti, Stefano; Zamboni, Giovanna; G., Calandra Buonaura; M., Serafini; Lui, Fausta; Baraldi, Patrizia; G., Rubboli; C. A., Tassinari; Nichelli, Paolo Frigio
abstract

Lesion and neuroimaging studies have demonstrated that the mesial temporal lobe is crucial for recognizing emotions from facial expressions. In humans, bilateral amygdala damage is followed by impaired recognition of facial expressions of fear. To evaluate the influence of unilateral mesial temporal lobe damage we examined recognition of facial expressions and functional magnetic resonance (fMRI) brain activation associated with incidental processing of fearful faces in thirteen mesial temporal lobe epilepsy (MTLE) patients (eight with right MTLE, five with left MTLE). We also examined the effect of early versus later damage, comparing subjects with hippocampal-amygdalar sclerosis (MTS) and seizures occurring before five years of age to epilepsy patients with late onset seizures. Fourteen healthy volunteers participated as controls. Neuropsychological testing demonstrated that the ability of right MTLE patients to recognize fearful facial expressions is impaired. Patients with early onset of seizures were the most severely impaired. This deficit was associated with defective activation of a neural network involved in the processing of fearful expressions, which in controls and left MTLE included the left inferior frontal cortex and several occipito-temporal structures of both hemispheres.

2004 - Ipsilesional neglect for left imaginal space [Articolo su rivista]
Cocchini, G.; Bartolo, A.; Nichelli, Paolo Frigio
abstract

non disponibile

2004 - Italian Neurological Society guidelines for the diagnosis of dementia: Revision l [Articolo su rivista]
M., Musicco; C., Caltagirone; S., Sorbi; V., Bonavita; M., Alberoni; P., Alfieri; M. C., Altavista; S., Amici; D., Antana; I., Appollonio; S., Avanzi; M., Bartolini; B., Bergamasco; C., Blundo; V., Bonavita; U., Bonuccelli; G., Cipriani; L., Bracco; A. C., Bruni; O., Bugiani; P., Caffara; C., Caltagirone; R., Perri; R., Camarda; N., Canal; A., Cannatà; G., Cantone; E., Carabelli; A., Cardei; S., Carlomagno; A. R., Casini; A., Cheldi; L., Cannnella; A., Citterio; A., Daniele; S., D'Anna; G., Del Curatolo; M., Del Pesce; R., Dell'Aversana; E., Farina; A. M., Fasanaro; M., Franceschi; P., Gabriele; G., Gainotti; E., Galante; V., Gallai; R., Gallasi; S., Bambina; M., Gasparini; G., Giaccone; F., Giubilei; M. P., Grassi; L., Grimaldi; S., Grioli; S. G., Bianca; M., Guarnirei; A., Batoli; B., Jandolo; F., Temolo; M., La Stilla; R. R., Latino; G. L., Lenzi; S., Lorusso; G., Magnani; S., Malaga; L., Manfredi; G., Marcon; A., Marcore; C., Mariani; S., Mearelli; A., Minore; M., Moleri; M., Morante; M., Morbin; P., Moretti; L., Murri; G., Rognoni; M., Musicco; Nichelli, Paolo Frigio; M., Paciello; A., Padovani; M., Paganini; R., Pantieri; P., Parisen; L., Parnetti; D., Partitico; S., Pasquale; B., Passerella; M., Perini; C., Pettinati; S., Piacentini; F., Piccoli; C., Piccolini; G., Pinardi; M. R., Piras; R., Cerchi; M., Principe; L., Provinciali; N., Pugliese
abstract

This paper presents the Italian guidelines for the diagnosis of dementia

2004 - Telephone-induced seizures: A new type of reflex epilepsy [Articolo su rivista]
R., Michelucci; E., Gardella; GJ de, Haan; F., Bisulli; A., Zaniboni; G., Cantalupo; Ca, Tassinari; P., Tinuper; C., Nobile; Nichelli, Paolo Frigio; DGA Kasteleijn Nolst, Trenité
abstract

Purpose: to report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone. Methods: Three patients with a history of telephone-induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video-EEG monitoring to record the reflex seizures also was performed in all cases. Results: The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with Subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient., a telephone-induced seizure arising from the dominant temporal lobe was recorded by means of video-EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans. Conclusions: We suggest that telephone epilepsy is a previously Unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.

2003 - A preliminary study of the cognitive mechanisms supporting time estimation [Articolo su rivista]
A., Venneri; S., Pestell; Nichelli, Paolo Frigio
abstract

Evidence from neuropsychological studies has suggested that verbal and visuospatial abilities might be differentially involved in time perception and that, because there is specialised competence, the two brain hemispheres might play different roles in time-keeping mechanisms. Reported are results of three experiments in which the time estimates of normal adults were tested using a prospective paradigm while they were engaged in concurrent secondary tasks requiring visuospatial or verbal memory and attention. Analysis showed no convincing evidence in support of a differential role of either verbal or visuospatial abilities in time estimation. The greatest disruption in time accuracy was detected when participants performed the time estimation tasks concurrently with secondary working memory tasks. These findings emphasize the importance of the involvement of specific cognitive systems rather than cognitive domains in the processing of temporal information.

2003 - Damage to the right hippocampal-amygdala formation during early infancy and recognition of fearful faces: neuropsychological and fMRI evidence in subjects with temporal lobe epilepsy [Articolo su rivista]
Meletti, Stefano; Benuzzi, Francesca; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

The article describes the deficits in emotion recognition observed in patients with early damage (during the first years of life) to the amygdala.

2003 - Distributed neural systems for temporal production: A functional MRI study [Articolo su rivista]
Nichelli, Paolo Frigio; M., Peterson; J., Grafman; Basso, Gianpaolo; C. M., Wharton
abstract

Using functional magnetic resonance imaging (fMRI), we investigated the neural substrates for computing time intervals. Five right-handed males were asked to judge if a digit probe belonged to a string of digits presented immediately before but to provide their response only after 1.5s had elapsed. This time estimation condition, compared with control working memory and motor tasks, was associated with increased activity in the middle occipital gyri, in the right inferior parietal lobe, and bilaterally in the prefrontal cortex. We argue that activity elicited in the occipital lobe provides duration information about visual stimuli that can be quantified at the level of the inferior parietal lobe. Comparison with time reference information depends on the bilateral prefrontal cortex.

2003 - Impaired facial emotion recognition in early-onset right mesial temporal lobe epilepsy. [Articolo su rivista]
Meletti, Stefano; Benuzzi, Francesca; G., Rubboli; G., Cantalupo; M., Stanzani Maserati; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

BACKGROUND: Anteromedial temporal lobe regions, particularly the amygdala, participate in the recognition of emotions from facial expressions. The authors studied the ability of facial emotion recognition (ER) in subjects with symptomatic epilepsy, evaluating whether mesial temporal lobe damage is related to an impairment in the recognition of specific emotions and whether the onset of seizures in a critical period of life could prevent the development of ER. METHODS: Groups included patients with temporal lobe epilepsy (TLE) with MRI evidence of mesial temporal sclerosis (MTS) (n = 33); patients with TLE with MRI evidence of temporal lobe lesions other than MTS (n = 30); and patients with extratemporal epilepsy (n = 33). Healthy volunteers (n = 50) served as controls. ER was tested by matching a facial expression with the name of one of the following basic emotions: happiness, sadness, fear, disgust, and anger. A face-matching task was used to control visuoperceptual abilities with face stimuli. RESULTS: No subject showed deficits in the face-matching task. ER was impaired in patients with right MTS, especially for fearful faces. Patients presenting left MTS, right or left temporal lobe lesions other than MTS, or extratemporal seizure foci showed ER performances similar to controls. In all subjects with right TLE, the degree of emotion recognition impairment was related to age at first seizure (febrile or afebrile) and age at epilepsy onset. CONCLUSIONS: Early-onset right-sided mesial temporal lobe epilepsy is the key substrate determining a severe deficit in recognizing emotional facial expressions, especially fear.

2003 - PL301L Tau Mutation and non-Alzheimer dementias in Itay [Articolo su rivista]
Mancuso, L.; Leone, L.; Filosto, M.; Tognoni, G.; Siciliano, G.; Nichelli, Paolo Frigio; Murri, L.
abstract

non disponiblie

2003 - Reorganization of neural circuit for fear recognition after anterior temporal lobectomy (selected for oral presentation). [Relazione in Atti di Convegno]
Benuzzi, Francesca; Meletti, Stefano; Zamboni, Giovanna; G., Calandra Buonaura; M., Serafini; Lui, Fausta; G., Rubboli; C. A., Tassinari; Nichelli, Paolo Frigio
abstract

Introduction: Several studies demonstrate the critical role on processing emotional stimuli of mesial temporal lobe structures, which are the common pathologic substrate of Temporal Lobe Epilepsy (TLE). We used fMRI to examine the reorganization of neural circuits underlying fear recognition after anterior temporal lobectomy in a group of TLE patients. Methods: Seven right-handed patients with a history of drug-resistant TLE (three with right and four with left TLE), were evaluated before and six months after lobectomy. Six right-handed healthy volunteers were tested as controls and re-tested after six months. Subjects were asked to make a gender decision task on fearful (F) and neutral faces (N). In a control condition (C) subjects were asked to detect a white square within scrambled faces. EPI data were acquired using a GE Signa HHS77 system at 1.5 Tesla (TR=3380 ms; TE=40 ms) across 16 axial 5 mm slices (64 x 64 matrix) and were analysed using SPM99. Before scanning, patients underwent a neuropsychological evaluation to assess their facial emotion recognition abilities. Results: Controls: A conjunction analysis (F and N) showed increased signal in occipito-temporal regions and mesial temporal lobe structures bilaterally, consistently with the activation of a specific face-selective network. This pattern of responses was similar at re-testing. Fearful expressions evoked activations in the inferior frontal and posterior cortex (fusiform gyrus and temporal lobe) bilaterally; re-test data showed activations reduced in extent and restricted to the left hemisphere. Patients: Preoperative and postoperative data showed regions of increased signal for faces similar to those found in controls. The activation of distinct regions for processing fearful faces was present in five of the seven patients; it was missing only in the two patients with right TLE and early amygdala damage. These two patients also failed in explicit recognition of fearful expressions. After surgery, they improved their performance at neuropsychological testing, and their fMRI data showed activation areas partially resembling the fearful activations found in controls and in left preoperative TLE patients. In the other patients the pattern of responses to fearful faces was not consistent on re-testing. Conclusions: In control subjects the neural network activated by faces (either neutral or fearful) did not vary on re-testing. Neither TLE nor anterior temporal lobectomy affected the response of this network. On the contrary, right early amygdala damage impaired explicit recognition of fearful expressions and it was associated with lack of fMRI activations during incidental processing of fearful faces. Re-test data showed that the selective pattern of activation to fearful expressions varied with the re-presentation of the emotional faces in controls and according to the side and the nature of the preoperative damage in TLE patients. Indeed, anterior temporal lobectomy improved emotional recognition in patients with early right amygdala damage and was associated with activation of a neural network for incidental processing of fearful faces. We suggest that an early discharging right mesial temporal lobe damage can prevent the brain from undergoing functional reorganization. Right anterior lobectomy, removing the discharging tissue, can release brain plasticity mechanisms, leading to recovery of emotion recognition.

2002 - Does anticipation of pain affect cortical nociceptive systems? [Articolo su rivista]
Porro, Carlo Adolfo; Baraldi, Patrizia; Pagnoni, Giuseppe; Serafini, M.; Facchin, P.; Maieron, Marta; Nichelli, Paolo Frigio
abstract

Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly afected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense (similar to30-40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.

2002 - Human brain language by functional magnetic lexical decision task processing areas identified resonance imaging using a lexical decision task [Articolo su rivista]
CALANDRA BUONAURA, Giovanna; Basso, Gianpaolo; Gorno Tempini, Ml; Serafini, M.; Pagnoni, Giuseppe; Baraldi, Patrizia; Porro, Carlo Adolfo; Nichelli, Paolo Frigio
abstract

The purpose of this study was to validate a functional magnetic resonance imaging (fMRI) paradigm to activate both anterior and posterior language areas while collecting accuracy and reaction time data on subjects' performance. The paradigm was based on alternating graphemic and lexical decision tasks. In line with the classical model of language organisation, based on lesion data, and with the results of previous neuroimaging studies, cortical activation associated with lexical decision-making was strongly lateralised to the left hemisphere and involved a network of regions in the frontal, temporal and parietal lobes. Single subject analysis demonstrated that the activation paradigm we propose is suitable for detecting language processing areas in humans for clinical studies.

2002 - Impaired recognition of facial expression of emotion in epileptic subjects with mesial temporal sclerosis [Abstract in Rivista]
Meletti, Stefano; Benuzzi, Francesca; G., Rubboli; E., Gardella; G., Cantalupo; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

2002 - Ipotesi e teorie sulla funione della corteccia prefrontale [Articolo su rivista]
Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

Non disponibile

2002 - Recognition of facial expressions of emotion in subjects with epilepsy and mesial temporal sclerosis | [Riconoscimento delle espressioni facciali emozionali in pazienti con epilessia e sclerosi temporo-mesiale] [Articolo su rivista]
Meletti, Stefano; Benuzzi, Francesca; G., Cantalupo; G., Rubboli; M., Stanzani Maserati; Nichelli, Paolo Frigio; C. A., Tassinari
abstract

The effect of unilateral amygdala damage on processing emotional stimuli is not clear. Since amygdala complex may be damaged unilaterally in subjects with Temporal Lobe Epilepsy (TLE), we examined the processing of emotional facial expression in TLE patients with MRI evidence of mesial temporal sclerosis (MTS). Emotion recognition was impaired in patients with right TLE and MTS at variance with epileptic subjects with other localization related epilepsy. The deficit in recognition was maximum for fearful faces. Moreover, during functional MRI patients with right MTS lacked the activation of separable mesial-temporal and frontal regions for the processing of fearful faces.

2002 - THE PROCESSING OF TEMPORAL INFORMATION IN THE FRONTAL LOBE [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

Not available

2001 - Explicit and incidental facial expression processing: an fMRI study [Articolo su rivista]
Gorno Tempini, Ml; Pradelli, S.; Serafini, M.; Pagnoni, Giuseppe; Baraldi, Patrizia; Porro, Carlo Adolfo; Nicoletti, Roberto; Umita, C.; Nichelli, Paolo Frigio
abstract

Considerable evidence indicates that processing facial expression involves both subcortical (amygdala and basal ganglia) and cortical (occipito-temporal, orbitofrontal, and prefrontal cortex) structures. However, the specificity of these regions for single types of emotions and for the cognitive demands of expression processing, is still unclear. This functional magnetic resonance imaging (fMRI) study investigated the neural correlates of incidental and explicit processing of the emotional content of faces expressing either disgust or happiness. Subjects were examined while they were viewing neutral, disgusted, or happy faces., The incidental task required subjects to decide about face gender, the explicit task to decide about face expression. In the control task subjects were requested to detect a white square in a greyscale mosaic stimulus. Results showed that the left inferior frontal cortex and the bilateral occipito-temporal junction responded equally to all face conditions. Several cortical and subcortical regions were modulated by task type, and by facial expression. Right neostriatum. and left amygdala were activated when subjects made explicit judgements of disgust, bilateral orbitofrontal cortex when they made judgement of happiness, and right frontal and insular cortex when they made judgements about any emotion.

2001 - Pattern of brain activity during mental imagery of eye movements [Abstract in Rivista]
Lui, Fausta; Baraldi, Patrizia; Benuzzi, Francesca; Fonda, Sergio; Maieron, Marta; Serafini, M; Nichelli, Paolo Frigio; Corazza, Ruggero; Porro, Carlo Adolfo
abstract

Previous studies have revealed that imagery of segmental motor events share a common neural substrate with actual motorperformance. The present study is aimed at investigating whether the cortical regions activated during imagined saccades overlap with areas activated during executed voluntary saccades.

2001 - The Apolipoprotein E genotype in patients affected by syndromes with focal cortical atrophy [Articolo su rivista]
C., Masullo; A., Daniele; Vm, Fazio; D., Seripa; C., Gravina; V., Filippini; D., Grossi; N., Fragassi; Nichelli, Paolo Frigio; M., Leone; G., Gainotti
abstract

The role of the Apolipoprotein E (APOE) alleles in syndromes associated with focal cerebral atrophy (fronto-temporal dementia, primary progressive aphasia, corticobasal degeneration) is still controversial. We studied the APOE allele distribution in 39 patients with clinically diagnosed syndromes associated with focal cerebral atrophy (FCA), in 50 patients with early-onset probable Alzheimer's disease (EOAD), and in 60 patients with late-onset probable AD (LOAD). The APOE genotype was determined from a blood sample, using polymerase chain reaction and restriction enzyme digestion. The APOE epsilon4 allele frequency was significantly higher in the EOAD (21.0%) and LOAD (33.3%) groups, but nor in the FCA group (5.1%), as compared with controls. In our population, the epsilon2 allele frequency was significantly higher in patients with FCA (12.8%) than in controls (4.8%). These results show that the APOE epsilon4 allele is not a risk factor for syndromes associated with FCA. The potential role of the epsilon2 allele in these syndromes needs further investigation. (C) 2001 Published by Elsevier Science Ireland Ltd.

2001 - The apolipoprotein E genotype in patients affected by syndromes with focal cortical atrophy (Erratum in vol 303, 2, pg 87-90, 2001) [Articolo su rivista]
Masullo, C; Daniele, A; Fazio, Vm; Seripa, D; Gravina, C; Filippini, V; Grossi, D; Fragassi, Na; Nichelli, Paolo Frigio; Leone, M; Gainotti, G.
abstract

non disponibile

2001 - UN CASO DI "MANO ALIENA" DOPO LESIONE EMISFERICA DESTRA [Articolo su rivista]
Farina, E.; Fioravanti, R.; Betinelli, A. DI MAIO S.; Nichelli, Paolo Frigio; Canal, N.
abstract

non disponibile

2000 - Aree corticali di rappresentazione bilaterale dei movimenti della mano [Articolo su rivista]
Baraldi, Patrizia; Serafini, M.; Pagnoni, G.; Crisi, G.; Basso, G. P.; Cettolo, V.; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

PET and fMRI studies have disclosed areas of activation in the ipsilateral primary sensorimotor cortex, which appears to be spatially much more extensive in the dominant hemisphere during sequential finger movements. This study directly investigated the presence and spatial distribution of controlateral, bilateral and ipsilateral cortical motor representations in both hemispheres using echo planar fMRI. FMRI disclosed different populations of neurons with specific functional characteristics in an anatomically defined area. There was no purely ipsilateral representation of movement; the ipsilateral component of cortical activation seems to reflect a population of neurons activated during movement of both right and left hands with greater extension in the dominant hemisphere. This bilateral population is presumably involved in movement planning. A second neuron population, activated only during the controlateral movement, was found in both hemispheres in the posterior portion of the precentral gyrus, probably corresponding to the primary motor area.

2000 - Brain pattern of activity during anticipation of pain [Articolo su rivista]
Porro, C. A.; Baraldi, P.; Pagnoni, G.; Serafini, M.; Murari, C.; Nichelli, P.
abstract

2000 - Functional imaging of recovery processes [Articolo su rivista]
Nichelli, Paolo Frigio; Benuzzi, Francesca; Basso, G; Buonaura, Gc; Frattini, D; Malagoli, M.
abstract

Non disponibile

2000 - Localizzazione cerebrale funzionale delle aree del linguaggio per mezzo di un compito di decisione lessicale [Articolo su rivista]
Basso, G.; Gorno-tempini, M. L.; Calandra Buonaura, G.; Serafini, M.; Pagnoni, G.; Mavilla, L.; Baraldi, Patrizia; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

The aim of this study was to develop a language rest to be used with functional magnetic resonance imaging (fMR1). The study is part of a larger project aimed at standardizing the rise of fMR1 in the clinical environment on brain lesioned patients selected for neurosurgery or language rehabilitation treatment. We present preliminary results based on the analysis of data obtained from ten, right-handed normal volunteers and one brain damaged patient.

2000 - Researching a differential impairment of frontal functions and explicit memory in early Parkinson's disease [Articolo su rivista]
E., Farina; G., Gattellaro; S., Pomati; E., Magni; A., Perretti; Ap, Cannata; Nichelli, Paolo Frigio; C., Mariani
abstract

An impairment at tasks sensitive to frontal lobe damage has been repeatedly reported in Parkinson's disease, but the exact nature of these deficits has not yet been clarified. Similarly, deficits of visuo-spatial functions have been frequently observed, but it is still debated whether verbal and visuo-spatial memory can be differentially affected. In this study we have compared the performance of 20 mild Parkinson's disease patients (I-II Hoehn and Yahr stage) and 18 matched normal controls, at tasks assessing frontal functions and explicit memory. We detected a selective deficit in set shifting and maintaining, without impairment in categorization and set formation. The lack of a selective increase in perseverative errors might indicate that perseverations either measure something different from set shifting or that they do not represent an index sensitive enough to set shifting impairment. Parkinson's disease patients were also significantly impaired at Raven's Progressive Matrices, a task assessing both frontal and visuo-spatial aspects. However, they did not show any differential impairment of visuo-spatial memory. Indeed, despite a trend of lower performance in visuo-spatial learning, memory performance of Parkinson's disease patients was significantly different from that of controls only at a free recall test which involved both verbal and visuo-spatial memory. We suggest the exploration of set shifting and maintaining to detect 'frontal' deficits in mild Parkinson's disease. We argue that Raven's Progressive Matrices is a valuable task for detecting subclinical cognitive deficits in Parkinson's disease, even if it does not show a specific profile of impairment in these patients. According to our results, a differential evaluation of verbal vs. visuo-spatial memory is not necessary in clinical practice, whilst free recall confirms its usefulness to detect subclinical impairments of memory functions.

2000 - Selective uppercase dysgraphia with loss of visual imagery of letter forms: A window on the organization of graphomotor patterns [Articolo su rivista]
N., Del Grosso Destreri; E., Farina; M., Alberoni; S., Pomati; Nichelli, Paolo Frigio; Mariani, Carlo
abstract

We report a patient who, after a left parieto-occipital lesion, showed alexia and selective dysgraphia for uppercase letters. He showed preserved oral spelling, associated with handwriting impairment in all written production; spontaneous writing, writing to dictation, real words, pseudowords, and single letters were affected. The great majority of errors were well-formed letter substitutions: most of them were located on the first position of each word, which the patient always wrote in uppercase las he used to do before his illness). The patient also showed a complete inability to access the visual representation of letters. As demonstrated by a stroke segmentation analysis, letter substitutions followed a rule of graphomotor similarity, We propose that the patient´s impairment was at the stage where selection of the specific graphomotor pattern for each letter is made and that the apparent selective disruption of capital case was due to a greater stroke similarity among letters belonging to the same case. We conclude that a visual format is necessary neither for spelling nor for handwriting.

1999 - Bilateral representation of sequential finger movements in human cortical areas [Articolo su rivista]
Baraldi, Patrizia; Porro, Carlo Adolfo; M., Serafini; Pagnoni, Giuseppe; Nichelli, Paolo Frigio; Corazza, Ruggero; C., Murari
abstract

The spatial distribution of cortical neural clusters activated during movement of either hand ('bilateral' population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential finger opposition task, using echo-planar functional magnetic resonance imaging. 'Bilateral' clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral finger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral finger movements was detected. These findings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.

1999 - Cortical coding of temporal and intensive aspects of pain: Echo-planar fMRI studies [Articolo su rivista]
Baraldi, P.; Pagnoni, G.; Serafini, M.; Murari, C.; Nichelli, P.; Porro, C. A.
abstract

1999 - Neuroanatomical correlates of recognizing emotional faces [Articolo su rivista]
Tempini, M. L. G.; Pradelli, S.; Pagnoni, G.; Baraldi, P.; Serafini, M.; Porro, C. A.; Nicoletti, R.; Umilta, C.; Nichelli, P.
abstract

1999 - Selective horizontal dysmetropsia following prestriate lesion [Articolo su rivista]
F., Frassinetti; Nichelli, Paolo Frigio; G., di Pellegrino
abstract

We describe a patient (P.S.) who, following a right prestriate lesion, reported that objects in the left visual field appeared distorted and smaller than those on the right. Other aspects of visual processing were remarkably unaffected, We carried out a series of size comparison tests using simple or complex stimuli and requiring different types of behavioural responses. We found that P.S. significantly underestimated the size of stimuli presented in her left visual field. When comparison tasks involved stimuli placed along the vertical axis or in the right visual field, P.S. performed well. The vertical and horizontal components of size distortion were found to be differentially affected. We conclude that size processing may be dissociated from other aspects of visual processing, such as form or colour processing, and depends critically on part of the occipital, prestriate areas (Brodmann areas 18-19).

1999 - Visuo-spatial and imagery disorders [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

The domain of neuroscience has had one of the most explosive growths in recent decades: within this development there has been a remarkable and renewed interest in the study of the relations between behaviour and the central nervous system. Part of this new attention is connected with the contribution of new technologies (PET, fMRI) permitting more precise mapping of neural structures responsible for cognitive functions and the development of new theoretical models of mental activities.The diffusion of new pathologies (for example the pattern of cognitive impairment associated with AIDS) has further enlarged the field of clinical neuropsychology. Finally there has been an expanding clinical interest in the understanding and management of age-related cognitive changes.

1998 - Cortical areas shared by contra- And ipsilateral sequential finger movements [Articolo su rivista]
Baraldi, P.; Porro, C. A.; Serafini, M.; Pagnoni, G.; Tavani, F.; Nichelli, P.
abstract

1998 - Kinematic analysis of the reach to grasp movement in Parkinson's and Huntington's disease subjects [Articolo su rivista]
C., Bonfiglioli; G., De Berti; Nichelli, Paolo Frigio; R., Nicoletti; U., Castiello
abstract

This experiment investigates the kinematic characteristics of the reach to grasp movement of Parkinson's and Huntington's disease subjects under two different experimental conditions. In the first condition subjects were required to perform the movement at a normal speed, while in the second condition they were required to perform the movement as fast as possible. Results showed that the kinematic parameterization of movement in Parkinson's disease subjects did not differ from that of age-matched control subjects for both the normal and the fast condition. However, the performances of Huntington's disease subjects appeared to be different when compared to the other two groups. Differences were mainly related to Huntington's disease patients' inability to properly define the temporal features of the movements. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

1998 - Memory, attention, and estimation of time [Articolo su rivista]
Venneri, A; Pestell, S; Gray, Cd; Della Sala, S; Nichelli, Paolo Frigio
abstract

Our experiments investigated the involvement of working memory and attention in time estimation. Healthy subjects performing a verbal time estimation task either alone or with a concurrent working memory or attentional secondary task were compared with three global amnesic patients performing the time task alone. Results showed that accuracy of performance in healthy subjects was markedly poorer when the secondary task involved working memory, paralleling a pronounced underestimation of time intervals in amnesic patients. No such effect was observed when the secondary task involved attention.

1997 - Impairment in dating and retrieving remote events in patients with early Parkinson's disease [Articolo su rivista]
A., Venneri; Nichelli, Paolo Frigio; G., Modonesi; M. A., Molinari; R., Russo; C., Sardini
abstract

Remote memory has been studied in a group of 25 non-demented patients with Parkinson's disease and their performance has been compared with that of 22 healthy control subjects. Only patients who scored greater than or equal to 27 on the mini mental state examination and with no anticholinergic treatment were included in the sample. A remote memory questionnaire was given, to evaluate memory for public events that occurred from 1966 to 1990. Each event was probed with five questions concerning its content and one for the date. Compared with healthy subjects, patients with Parkinson's disease were significantly impaired both in recalling the content and in dating remote events. These results support the claim that remote memory in patients with Parkinson's disease is disrupted independently of dementia. This impairment might result from a dysfunction at the level of the circuit connecting the basal ganglia to the frontal lobes.

1996 - Accidental choke cherry poisoning: Early symptoms and neurological sequelae of an unusual case of cyanide intoxication [Articolo su rivista]
Pentore, R; Venneri, Annalena; Nichelli, Paolo Frigio
abstract

We report the case of a 56-year-old woman who was accidentally poisoned when size ingested choke cherries whose pulp contained cyanide, and describe the acute clinical picture, the neurological sequelae and the neuroradiological findings. After recovery from coma the patient showed signs of a parkinsonian syndrome, retrobulbar neuritis and sensory-motor neuropathy. MRI showed abnormal signal intensities involving the basal ganglia. Since no memory deficits were observed, we argue that the parkinsonian syndrome was caused by cyanide intoxication rather than by subcortical damage due to hypoxia.

1996 - I disturbi spaziali e visuo-immaginativi. [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

Sono analizzati i disturbi visuo-spaziali e visuo-immaginativi successivi a lesioni cerebrali focali e a patologie neurodegenerative

1996 - Perceptual timing in cerebellar degeneration [Articolo su rivista]
Nichelli, Paolo Frigio; D., Alway; J., Grafman
abstract

This study examined rime perception in 12 patients with cerebellar degeneration (CD) and in 13 normal controls (NC). We used a time bisection procedure with four interval conditions (100-900 msec; 8-32 sec; 100-600 msec; 100-325 msec). Each subject´s bisection point, discrimination ability (the Weber ratio) and precision (the inverse of the proportion of unexplained variance) was calculated for each condition. CD patients´ performance on the 100-900 msec time bisection condition suggested a possible time discrimination deficit, which was confirmed with intervals in the range of 100-600 msec. Time discrimination was normal on the 100-325 msec condition and impaired on the 8-32 sec bisection task. However, when discriminating long intervals, CD patients also showed a precision deficit, which points to impaired sustained attention and/or decision processes. Our findings corroborate the view that cerebellar timing processes are not limited to the motor system but are also used in perceptual computations. Copyright

1996 - Time perception in a neglected space [Articolo su rivista]
Basso, Gianpaolo; Nichelli, Paolo Frigio; Frassinetti, F; Dipellegrino, G.
abstract

We have studied the distortion of perceived time in a patient with left neglect. This patient consistently overestimated the duration of stimuli in the neglected space. Overestimation was observed both with an interval comparison (300/700 ms) and with a time production (1 s) paradigm. We suggest that encoding duration in the hundreds of milliseconds range is a process based on an internal clock mechanism. The functioning of that clock varies as a function of the processing load.

1996 - Time perception measurements in neuropsychology [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

The interest in the concept of time has a long history and has been a topic of study for a wide range of investigators. No change can take place without specification of time. While philosophers and physicists have been intrigued by the concept of subjective perception of time and its relationship to real time, natural scientists have been concerned mainly with investigating time as a factor in understanding the behaviour of animals from the migratory habits of birds to the periodical breeding cycles. The immense bulk of temporal perception studies, the variety of approaches, methods of measurement and even terminology has led to a difficulty in reaching a global interpretation of the results.This book aims to give an integrative approach of time sense and to focus the analysis on temporal factors in the processing of movement, trying to link temporal perception studies in the final common pathway, that is motion. To give some clues of human brain integrative processes at higher levels. And, finally, to clarify the neurophysiological substrate of these operations.

1995 - DEVELOPMENTAL-TRENDS IN IMPLICIT AND EXPLICIT MEMORY - A PICTURE COMPLETION STUDY [Articolo su rivista]
Russo, R; Nichelli, Paolo Frigio; Gibertoni, M; Cornia, C.
abstract

The presence of a developmental trend in the magnitude of perceptual repetition priming was assessed in two experiments using picture completion. preschool children, 6-year-old children, and young adults showed the same amount of repetition priming when both a proportional measure of priming (Snodgrass, 1989) was used and spurious explicit memory influences were partialled out from the implicit task. This finding was contrasted with the age-associated improvement in explicit memory as measured by cued and free recall. These results highlight the relevance of controlling explicit memory influence on implicit memory tasks in determining the effect of a variable on implicit processes, moreover they provide further support for the distinction between implicit and explicit memory.

1995 - Duration processing after frontal lobe lesions [Articolo su rivista]
Nichelli, Paolo Frigio; Clark, K; Hollnagel, C; Grafman, J.
abstract

non disponibile

1995 - Relations between attentional and intentional neural systems [Articolo su rivista]
Basso, G; Nichelli, Paolo Frigio
abstract

This study explored whether preparing an arm movement influences detection of a visual stimulus. We cued subjects to respond with either a rightward or a leftward movement to the appearance of a stimulus located either in the centre, in the left, or in the right visual field. Programming a movement toward a lateral direction enhanced visual attention at that side. Rightward movements were associated with an attentional cost only for responses to a central location, while leftward movements slowed response latencies to both central and right-sided stimuli. We hypothesized that programming a rightward movement depends on the activation of intentional centers in either cerebral hemisphere. On the contrary, leftward movements might be only driven by the contralateral hemisphere.

1995 - Right hemisphere developmental learning disability: A case study [Articolo su rivista]
Nichelli, Paolo Frigio; Venneri, Annalena
abstract

We report a case study of a 22-year-old man with a developmental learning disorder consisting of arithmetic difficulties, visuo-spatial deficits and emotional difficulties. Language abilities and verbal learning were remarkably spared. The clinical picture was consistent with the diagnosis of 'Right Hemisphere Developmental Learning Disability' (RHDLD) as described by Weintraub and Mesulam (Archives of Neurology 1983; 40: 463-8). Computed tomography and magnetic resonance imaging scans were normal, but a positron emission tomography scan revealed a marked hypometabolism of the right hemisphere, supporting the claim that RHDLD is indeed associated with functional abnormalities of the right hemisphere.

1995 - Where the brain appreciates the moral of a story [Articolo su rivista]
Nichelli, Paolo Frigio; J., Grafman; P., Pietrini; K., Clark; Ky, Lee; R., Miletich
abstract

To identify the distributed brain regions used for appreciating the grammatical, semantic and thematic aspects of a story, regional cerebral blood flow was measured with positron emission tomography in nine normal volunteers during the reading of Aesop's fables. In four conditions, subjects had to monitor the fables for font changes, grammatical errors, a semantic feature associated with a fable character, and the moral of the fable. Both right and left prefrontal cortices were consistently, but selectively, activated across the grammatical, semantic, and moral conditions. In particular, appreciating the moral of a story required activating a distributed set of brain regions in the right hemisphere which included the temporal and prefrontal cortices. These findings emphasize that story processing engages a widely distributed network of brain regions, a subset of which become preferentially active during the processing of a specific aspect of the text.

1994 - AGREEMENT IN THE CLINICAL-DIAGNOSIS OF DEMENTIA - EVALUATION OF A CASE SERIES WITH MILD COGNITIVE IMPAIRMENT [Articolo su rivista]
Solari, A; Cossa, Fm; Denes, F; Gainotti, G; Grossi, D; Nichelli, Paolo Frigio; Filippini, G.
abstract

Interobserver agreement in the clinical diagnosis of dementia among four neurologists was evaluated. The physicians, masked to the original diagnoses, independently reviewed the clinical records of 50 outpatients consulting either the Ist University Neurology Department of Milan or the Neuropsychology Unit of the Medical Center of Veruno (Novara) for suspected cognitive impairment, during a 6-month period. The records contained patients' medical and neurological history, results of neuropsychological testing, laboratory tests, cerebral computed tomography and other investigations. For each patient, the raters had to provide both a diagnosis concerning the presence or absence of dementia and to assign an analytical diagnosis to all the dementia cases. The kappa statistic was used as a measure of interrater reliability. The level of agreement on the primary diagnosis of dementia was moderate (kappa = 0.49); with respect to the nosological diagnoses, the kappa values ranged from 0.16 for depression to 0.80 for multiinfarct dementia.

1994 - Brain activity in chess playing [Articolo su rivista]
Nichelli, Paolo Frigio; J., Grafman; P., Pietrini; D., Alway; Jc, Carton; R., Miletich
abstract

non disponibile

1994 - IMPLICIT AND EXPLICIT MEMORY IN PATIENTS WITH PARKINSONS-DISEASE WITH AND WITHOUT DEMENTIA [Articolo su rivista]
Appollonio, I; Grafman, J; Clark, K; Nichelli, Paolo Frigio; Zeffiro, T; Hallett, M.
abstract

Objective: To study explicit and implicit memory processes in patients with Parkinson's disease. Design: Case-control design. All subjects were given a neuropsychological test battery, and the test scores were compared among the groups. Setting: Government-funded research facility. All subjects were examined as outpatients. Patients: We tested nondemented (n=13) and demented (n=5) patients with Parkinson's disease and normal controls (n=12) matched for age, gender, and educational level. Main Outcome Measures: Memory for verbal and pictorial stimuli under both explicit and implicit retrieval conditions. Results: Both nondemented and demented patients with Parkinson's disease exhibited impairment on tests of explicit memory. Their impairment could be graded based on the level of effort required by the task: impaired free recall in nondemented patients and impaired free recall, cued recall, and recognition in demented patients. By contrast, neither group showed evidence of impairment on automatic (modality monitoring and word frequency estimation) or implicit (word and picture fragment identification) memory tasks. Correlation analyses did not support any association between the effortful memory deficits and neurologic variables, mood, or performance on executive function tests. Conclusions: Memory deficits in patients with Parkinson's disease primarily involve the conscious, effortful strategic aspects of searching long-term memory.

1994 - INDUCTION OF A RECALL DEFICIT BY RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION [Articolo su rivista]
Grafman, J; Pascualleone, A; Alway, D; Nichelli, Paolo Frigio; Gomeztortosa, E; Hallett, M.
abstract

WE used rapid-rate, repetitive transcranial magnetic stimulation (rTMS) for the noninvasive study of verbal recall. Five right-handed normal subjects were studied. Recall followed immediately after presentation of a 12-word list. Focal rTMS was applied with a figure eight coil in trains of 500 ms duration to F7, F8, T5, T6, P3, P4, or 01, 02 at latencies of 0, 250, 500, or 1000 ms during word list presentation. Recall was consistently significantly diminished only after left mid-temporal and bilateral dorsofrontal rTMS at both 0 and 250 ms latencies. We conclude that rTMS may be useful as a non-invasive tool for the study of verbal memory processes.

1994 - WORD-FREQUENCY MONITORING IN PARKINSON DISEASE - AN ANALYSIS OF ACCURACY AND PRECISION [Articolo su rivista]
Nichelli, Paolo Frigio; Appollonio, I; Clark, K; Grafman, J.
abstract

The judgment of frequency of occurrence of stimuli appearing in a task is a complicated decision. This decision can be independently analyzed using estimates of subject accuracy (where their estimate resembles the true frequency of the stimuli) and precision (sensitive to response bias). In this study, the accuracy and precision of Parkison's disease (PD) patients estimates of the frequency of occurrence of word stimuli were analyzed. The results indicated that the accuracy estimates of PD patients were not significantly different from normal controls whereas their precision of frequency judgments was impaired. Poorer precision scores were associated with fewer categories achieved on the Wisconsin Card Sorting Test. Using accuracy and precision estimates should improve the characterization of the cognitive processes required in frequency judgments.

1993 - ANARTHRIA IMPAIRS SUBVOCAL COUNTING [Articolo su rivista]
Cubelli, R; Nichelli, Paolo Frigio; Pentore, R.
abstract

We studied subvocal counting in two pure anarthric patients. Analysis showed that they performed definitively worse than normal subjects free to articulate subvocally and their scores were in the lower bounds of the performances of subjects suppressing articulation. These results suggest that subvocal counting is impaired after anarthria.

1993 - HORIZONTAL AND VERTICAL NEGLECT DYSLEXIA [Articolo su rivista]
Nichelli, Paolo Frigio; Venneri, A; Pentore, R; Cubelli, R.
abstract

This case study concerns a 25-year-old right-handed male patient (G.G.) with post-traumatic lesions involving the right temporal and occipital lobe as well as the basal forebrain of the same side. G.G., who had a visual field defect almost limited to the upper left quadrant, showed both left horizontal and lower vertical neglect dyslexia, disproportionately severe when compared with left and lower visuo-spatial neglect. This is the first case report of a patient whose neglect dyslexia for vertical stimuli depended upon stimulus orientation, i.e., errors affected the final letters of top-down words and the initial letters of the bottom-up ones. This implies that neglect dyslexia can affect the internal letter shape map not only along the horizontal, but also along the vertical axis.

1993 - PRECISION AND ACCURACY OF SUBJECTIVE TIME-ESTIMATION IN DIFFERENT MEMORY DISORDERS [Articolo su rivista]
Nichelli, Paolo Frigio; Venneri, Annalena; Molinari, M; Tavani, F; Grafman, J.
abstract

The aim of this study was to evaluate how different memory disorders affect subjective time durations. For this purpose we studied prospective time estimations in 4 amnesic (A) and in 15 Alzheimer's disease (AD) patients, and compared their performance with that of 5 matched young normal controls (YC) and 15 elderly subjects (EC). For the short-time durations we asked the subject to repeatedly reproduce a standard interval of 1 s. To test how subjects evaluated longer time durations, we choose a verbal estimation procedure. The subjects' task was to read either 5, 10, 20, or 40 digits appearing one at a time, while concurrently keeping the rhythm of 1 key press per second. At the end of each sequence, subjects had to judge the elapsed time from the beginning of the trial. Results showed that amnesics can correctly reproduce 1-s intervals. However, their accuracy of verbal estimates of longer durations was severely impaired. AD patients showed increased variability on repeated reproduction of 1-s intervals and were both inaccurate and imprecise in their verbal estimate of longer durations. Using the framework of the Scalar Timing Model, we conclude that amnesic patients exhibit a deficit in encoding and storing the current time for intervals that exceed their short-term memory range, while AD patients show a pattern of deficit that is explained by a more widespread involvement of both the clock, the memory, and the decisional mechanisms.

1993 - The neuropsychology of human temporal information processing [Capitolo/Saggio]
Nichelli, Paolo Frigio
abstract

not available

1992 - INNER SPEECH IN ANARTHRIA - NEUROPSYCHOLOGICAL EVIDENCE OF DIFFERENTIAL-EFFECTS OF CEREBRAL-LESIONS ON SUBVOCAL ARTICULATION [Articolo su rivista]
Cubelli, R; Nichelli, Paolo Frigio
abstract

The role of articulation in verbal short-term memory was investigated in two anarthric patients, C.M. and F.C., both showing normal comprehension for written and spoken language, above average intelligence and visuo-spatial abilities. Based on experimental results, we propose that subvocal articulation might be impaired in anarthric patients in different ways, according to the site of lesion: in 'locked-in' patients only the articulatory rehearsal processes necessary to enhance memory performances is involved, while in cortical anarthric patients the lesion affects the articulatory recoding processes involved in transferring visually presented material into an articulatory form for better retention.

1991 - APPERCEPTIVE AND ASSOCIATIVE FORMS OF PROSOPAGNOSIA [Articolo su rivista]
Derenzi, E; Faglioni, P; Grossi, D; Nichelli, Paolo Frigio
abstract

Three prosopagnosic patients were given four face tests, two perceptual (an unknown face identification test and an age estimation test) and two also implying memory (a familiarity check test and a famous face recognition test). The patients' performance was assessed with reference to the score distribution of the normal population. A patient was found to fail both perceptual and mnestic tests, without any noticeable difference between them. Also the second patient had poor scores on both kinds of tests, but his impairment was significantly greater on the perceptual ones. The third patient, on the contrary, showed no perceptual deficit and only failed the mnestic tests. His inability to recognize the individuality of an item among members of the same category was strictly confined to faces and never present for other classes of stimuli (cars, coins, personal belongings). This finding is supportive of the thesis that in a few patients the deficit underlying prosopagnosia is face specific.

1991 - DIFFERENT PATTERNS OF DISSOCIATION IN UNILATERAL SPATIAL NEGLECT [Articolo su rivista]
Cubelli, R; Nichelli, Paolo Frigio; Bonito, V; Detanti, A; Inzaghi, Mg
abstract

The aim of this paper is to discuss the issue of dissociations found in unilateral spatial neglect according to the modality of space exploration and the nature of the task. For this purpose we present a reanalysis of the data from a recent paper of Gentilini et al. (1989) comparing visual and blindfolded exploration of a computer keyboard and discuss the performance of a left-brain-damaged patient with right visuospatial neglect and left-sided neglect dyslexia. We conclude that unilateral spatial neglect cannot be interpreted as a disruption of a single attentional mechanism, but rather it reflects impaired attentional mechanisms at several levels of cognitive processing

1990 - Giovanni Brugnoli and the origin of neuropsychology in Italy [Articolo su rivista]
Nichelli, Paolo Frigio; Cubelli, R.
abstract

We report the story of the very first steps of neuropsychologicy in Italy

1989 - A neuropsychological model for the role of articulation in short-term memory and reading comprehension [Capitolo/Saggio]
Nichelli, Paolo Frigio; R., Cubelli
abstract

We present a model of the role of articulation in short-term memory and reading coprehension based on observations of patients with anathria

1989 - Anarthria and verbal short-term memory [Capitolo/Saggio]
R., Logie; R., Cubelli; S., Della Sala; M., Alberoni; Nichelli, Paolo Frigio
abstract

not available