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Francesca BENUZZI

Professore Associato
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Neuroscienze


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Pubblicazioni

2022 - Can Disruption of Basal Ganglia-Thalamocortical Circuit in Wilson Disease Be Associated with Juvenile Myoclonic Epilepsy Phenotype? [Articolo su rivista]
Rossi, J.; Cavallieri, F.; Giovannini, G.; Benuzzi, F.; Ballotta, D.; Vaudano, A. E.; Ferrara, F.; Contardi, S.; Pietrangelo, A.; Corradini, E.; Lui, F.; Meletti, S.
abstract

In this paper, we describe the multimodal MRI findings in a patient with Wilson disease and a seizure disorder, characterized by an electroclinical picture resembling juvenile myoclonic epilepsy. The brain structural MRI showed a deposition of ferromagnetic materials in the basal ganglia, with marked hypointensities in T2-weighted images of globus pallidus internus bilaterally. A resting-state fMRI study revealed increased functional connectivity in the patient, compared to control subjects, in the following networks: (1) between the primary motor cortex and several cortical regions, including the secondary somatosensory cortex and (2) between the globus pallidus and the thalamo-frontal network. These findings suggest that globus pallidus alterations, due to metal accumulation, can lead to a reduction in the normal globus pallidus inhibitory tone on the thalamo-(motor)-cortical pathway. This, in turn, can result in hyperconnectivity in the motor cortex circuitry, leading to myoclonus and tonic-clonic seizures. We suppose that, in this patient, Wilson disease generated a ‘lesion model’ of myoclonic epilepsy.


2022 - Eliciting Implicit Awareness in Alzheimer’s Disease and Mild Cognitive Impairment: A Task-Based Functional MRI Study [Articolo su rivista]
Tondelli, M.; Benuzzi, F.; Ballotta, D.; Molinari, M. A.; Chiari, A.; Zamboni, G.
abstract

Background: Recent models of anosognosia in dementia have suggested the existence of an implicit component of self-awareness about one’s cognitive impairment that may remain preserved and continue to regulate behavioral, affective, and cognitive responses even in people who do not show an explicit awareness of their difficulties. Behavioral studies have used different strategies to demonstrate implicit awareness in patients with anosognosia, but no neuroimaging studies have yet investigated its neural bases. Methods: Patients with amnestic mild cognitive impairment and dementia due to Alzheimer’s disease underwent functional magnetic resonance imaging (fMRI) during the execution of a color-naming task in which they were presented with neutral, negative, and dementia-related words (Dementia-Related Emotional Stroop). Results: Twenty-one patients were recruited: 12 were classified as aware and 9 as unaware according to anosognosia scales (based on clinical judgment and patient-caregiver discrepancy). Behavioral results showed that aware patients took the longest time to process dementia-related words, although differences between word types were not significant, limiting interpretation of behavioral results. Imaging results showed that patients with preserved explicit awareness had a small positive differential activation of the posterior cingulate cortex (PCC) for the dementia-related words condition compared to the negative words, suggesting attribution of emotional valence to both conditions. PCC differential activation was instead negative in unaware patients, i.e., lower for dementia-related words relative to negative-words. In addition, the more negative the differential activation, the lower was the Stroop effect measuring implicit awareness. Conclusion: Posterior cingulate cortex preserved response to dementia-related stimuli may be a marker of preserved implicit self-awareness.


2022 - Pure word deafness: a case report of an atypical manifestation of Alzheimer’s disease [Articolo su rivista]
Salemme, S.; Benuzzi, F.; Fiondella, L.; Carbone, C.; Vinceti, G.; Magarelli, S.; Molinari, M. A.; Malagoli, M.; Zamboni, G.; Chiari, A.
abstract

Auditory agnosia refers to the impairments in sound recognition despite intact hearing and written language abilities. When auditory agnosia is specific to spoken language, it can be indicated as pure word deafness (PWD), which is characterized by the isolated difficulty in understanding spoken language, despite preserved reading comprehension, recognition of nonverbal sounds, and production of written and spoken language.


2021 - Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep [Articolo su rivista]
Betta, Monica; Handjaras, Giacomo; Leo, Andrea; Federici, Alessandra; Farinelli, Valentina; Ricciardi, Emiliano; Siclari, Francesca; Meletti, Stefano; Ballotta, Daniela; Benuzzi, Francesca; Bernardi, Giulio
abstract

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.


2021 - Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1 [Articolo su rivista]
Ballotta, D.; Talami, F.; Pizza, F.; Vaudano, A. E.; Benuzzi, F.; Plazzi, G.; Meletti, S.
abstract

Introduction: functional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset. Methods: Fifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala. Results: compared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen. Conclusion: in NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.


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 - Influence of anxiety and alexithymia on brain activations associated with the perception of others’ pain in autism [Articolo su rivista]
Lassalle, Amandine; Zürcher, Nicole R.; Porro, Carlo A.; Benuzzi, Francesca; Hippolyte, Loyse; Lemonnier, Eric; Åsberg Johnels, Jakob; Hadjikhani, Nouchine
abstract

The circumstances under which empathy is altered in ASD remain unclear, as previous studies did not systematically find differences in brain activation between ASD and controls in empathy-eliciting paradigms, and did not always monitor whether differences were primarily due to ASD “per se”, or to conditions overlapping with ASD, such as alexithymia and anxiety. Here, we collected fMRI data from 47 participants (22 ASD) viewing pictures depicting hands and feet of unknown others in painful, disgusting, or neutral situations. We computed brain activity for painful and disgusting stimuli (vs. neutral) in whole brain and in regions of interest among the brain areas typically activated during the perception of nociceptive stimuli. Group differences in brain activation disappeared when either alexithymia or anxiety – both elevated in the ASD group – were controlled for. Regression analyses indicated that the influence of symptoms was mainly shared between autistic symptomatology, alexithymia and anxiety or driven by unique contributions from alexithymia or anxiety. Our results suggest that affective empathy may be affected in ASD, but that this association is complex. The respective contribution of alexithymia and anxiety to decreased affective empathy of people with ASD may be due to the association of those psychiatric conditions with reduced motor resonance/Theory of Mind.


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


2019 - Words hurt: common and distinct neural substrates between physical and semantic pain [Poster]
Borelli, Eleonora; Lui, Fausta; Benuzzi, Francesca; Cacciari, Cristina; Porro, Carlo Adolfo
abstract


2018 - Effect of visual stimuli of pain on empathy brain network in people with and without Autism Spectrum Disorder [Articolo su rivista]
Lassalle, Amandine; Zürcher, Nicole R; Hippolyte, Loyse; Billstedt, Eva; Porro, Carlo A; Benuzzi, Francesca; Solomon, Patricia; Prkachin, Kenneth M; Lemonnier, Eric; Gillberg, Christopher; Åsberg Johnels, Jakob; Hadjikhani, Nouchine
abstract

The extent to which affective empathy is impaired in Autism Spectrum Disorder (ASD) remains unclear, as some—but not all—previous neuroimaging studies investigating empathy for pain in ASD have shown similar activation levels to those of neurotypicals individuals. These inconsistent results could be due to the use of different empathy-eliciting stimuli. While some studies used pictures of faces exhibiting a painful expression, others used pictures of limbs in painful situations. In this study, we used fMRI to compare activation in areas associated with empathy processing (empathy network) for these two types of stimuli in 31 participants (16 with ASD, 15 controls). We found a group difference in the inferior frontal gyrus (IFG) and the thalamus when participants viewed stimuli of limbs in painful situations, but not when they viewed face stimuli with a painful expression. Both groups of participants activated their empathy network more when viewing pictures of limbs in painful situations than when viewing pictures of faces with a painful expression; this increased activation for limbs versus faces was significantly enhanced in controls relative to ASD participants, especially in the secondary somatosensory cortex (SII). Our findings suggest that empathy defect of people with ASD is contingent upon the type of stimuli used, and may be related to the level of Mirror Neuron System involvement, as brain regions showing group differences (IFG, SII) underlie embodiment. We discuss the potential clinical implications of our findings in terms of developing interventions boosting the empathetic abilities of people with ASD.


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 - Episodic future thinking and future-based decision-making in a case of retrograde amnesia [Articolo su rivista]
De Luca, F.; Benuzzi, F.; Bertossi, E.; Braghittoni, D.; di Pellegrino, G.; Ciaramelli, E.
abstract

We investigated episodic future thinking (EFT) and future-based cognition and decision-making in patient SG, who developed a dense retrograde amnesia following hypoxia due to a cardiac arrest. Despite intact general cognitive and executive functioning, SG was unable to remember events from his entire lifetime. He had, however, relatively spared anterograde memory and general semantic knowledge. Voxel-based morphometry detected a reduction of gray matter in the thalamus, cerebellum and fusiform gyrus bilaterally, and, at a reduced threshold, in several regions of the autobiographical memory network, including the hippocampi. We show that SG is unable to imagine personal future events, but can imagine fictitious events not self-relevant and not located in subjective time. Despite severely impaired EFT, SG shows normal attitudes towards the future time, and normal delay discounting rates. These findings suggest that retrieval of autobiographical information from long-term memory is necessary for EFT. However, relatively spared anterograde memory and general semantic knowledge may be sufficient to allow construction of fictitious experiences. As well, EFT is not necessary to drive future-oriented cognition and choice. These findings highlight the relation between autobiographical memory and EFT, and the fractionation of human temporal consciousness. Moreover, they contribute to our understanding of retrograde amnesia as an impairment of memory as well as future thinking.


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 - Pain mirrors: Neural correlates of observing self or others' facial expressions of pain [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Ardizzi, Martina; Ambrosecchia, Marianna; Ballotta, Daniela; Righi, Sara; Pagnoni, Giuseppe; Gallese, Vittorio; Porro, Carlo Adolfo
abstract

Facial expressions of pain are able to elicit empathy and adaptive behavioral responses in the observer. An influential theory posits that empathy relies on an affective mirror mechanism, according to which emotion recognition relies upon the internal simulation of motor and interoceptive states triggered by emotional stimuli. We tested this hypothesis comparing representations of self or others' expressions of pain in nineteen young healthy female volunteers by means of functional magnetic resonance imaging (fMRI). We hypothesized that one's own facial expressions are more likely to elicit the internal simulation of emotions, being more strictly related to self. Video-clips of the facial expressions of each volunteer receiving either painful or non-painful mechanical stimulations to their right hand dorsum were recorded and used as stimuli in a 2 × 2 (Self/Other; Pain/No-Pain) within-subject design. During each trial, a 2 s video clip was presented, displaying either the subject's own neutral or painful facial expressions (Self No-Pain, SNP; Self Pain, SP), or the expressions of other unfamiliar volunteers (Others' No-Pain, ONP; Others' Pain, OP), displaying a comparable emotional intensity. Participants were asked to indicate whether each video displayed a pain expression. fMRI signals were higher while viewing Pain than No-Pain stimuli in a large bilateral array of cortical areas including middle and superior temporal, supramarginal, superior mesial and inferior frontal (IFG) gyri, anterior insula (AI), anterior cingulate (ACC), and anterior mid-cingulate (aMCC) cortex, as well as right fusiform gyrus. Bilateral activations were also detected in thalamus and basal ganglia. The Self vs. Other contrast showed signal changes in ACC and aMCC, IFG, AI, and parietal cortex. A significant interaction between Self and Pain [(SP vs. SNP) > (OP vs. ONP)] was found in a pre-defined region of aMCC known to be also active during noxious stimulation. These findings demonstrate that the observation of one's own and others' facial expressions share a largely common neural network, but self-related stimuli induce generally higher activations. In line with our hypothesis, selectively greater activity for self pain-related stimuli was found in aMCC, a medial-wall region critical for pain perception and recognition.


2017 - Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil [Articolo su rivista]
Prontera, A; Baroni, S; Marudi, A; Valzania, F; Feletti, A; Benuzzi, F; Bertellini, E; Pavesi, G
abstract


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 - 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 & 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.


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 - 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 - 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 - 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 - 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 - Generalized Spike and Waves: Effect of Discharge Duration on Brain Networks as Revealed by BOLD fMRI. [Articolo su rivista]
Pugnaghi, M.; Carmichael, D. W.; Vaudano, A. E.; Chaudhary, U. J.; Benuzzi, Francesca; Bonaventura, C. D.; Giallonardo, A. T.; Rodionov, R.; Walker, M. C.; Duncan, J. S.; Meletti, Stefano; Lemieux, L.
abstract

In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG-fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG-fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.


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 - Prognostic factors and health-related quality of life in ocular myasthenia gravis (OMG) [Articolo su rivista]
Ariatti, A.; Stefani, M.; Miceli, P.; Benuzzi, F.; Galassi, G.
abstract

We evaluate the factors predictive of prognosis in 91 Caucasian patients affected by ocular myasthenia gravis (OMG), followed at our Institution during an observational time, ranging from 12 to 240 months. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was used to grade the disease severity. We considered as outcome measures the variation in two subscores, ocular (O-QMG) and nonocular (NO-QMG); the last one reflected bulbar, neck, extremity functions. None of the independent variables evaluated for association with the outcome, as age of onset, type of therapy, length of interval between first and last examinations, and presence of antibodies to acetylcholine receptors (AChR-Abs) significantly affected the evolution of O-QMG and of NO-QMG. Health-related quality of life (HRQol) was assessed in 63 patients. Variations of diplopia or ptosis did not affect significantly physical (PCS) or mental composite subscores (MCS) of the Short-Form Health Survey (SF-36). Human leukocyte antigen (HLA) genotyping was studied to explore whether HLA class I and II allelic distribution differed among MG patients and controls. None of the studied HLA alleles significantly differed between OMG patients and controls. Similarly, none of the alleles with frequencies higher than 15% either in OMG patients or in controls was significantly associated, after Bonferroni correction, with the presence or absence of anti-AChR-Abs in serum. © 2014 Informa Healthcare USA, Inc.


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 - Temporal lobe epilepsy and emotion recognition without amygdala: a case study of Urbach-Wiethe disease and review of the literature [Articolo su rivista]
Meletti, Stefano; Cantalupo, Gaetano; Santoro, Francesca; Benuzzi, Francesca; Marliani, Anna Federica; Tassinari, Carlo Alberto; Rubboli, Guido
abstract

We describe the epilepsy features and emotion recognition abilities (recognition of basic facial emotions and recognition of emotional prosody) in a patient with Urbach-Wiethe disease with bilateral amygdala calcifications. Our data, supported by ictal video-EEG recording, indicated that our patient suffered from mesial temporal lobe epilepsy. Emotion recognition abilities were compared to those of healthy controls and those of patients with bilateral mesial temporal lobe epilepsy. Our patient showed a selective impairment of the recognition of facial expression of fear, whereas recognition of emotional prosody was preserved, in contrast to bilateral mesial temporal lobe epilepsy patients that presented with deficits in both domains. We also reviewed the literature on epilepsy in Urbach-Wiethe disease (41 patients). Our findings suggest that in Urbach-Wiethe disease, the circumscribed damage of both amygdalae results in a selective dysfunction of fearful face processing, in contrast to bilateral mesial temporal lobe epilepsy patients who present with a widespread and multimodal impairment in the judgement of emotional stimuli.


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 - Facial emotion recognition in childhood: the effects of febrile seizures in the developing brain. [Articolo su rivista]
G., Cantalupo; Meletti, Stefano; A., Miduri; S., Mazzotta; L., Rios Pohl; Benuzzi, Francesca; F., Pisani; C. A., Tassinari; G., Cossu
abstract

It has been documented that anteromedial temporal lobe dysfunction can cause impairment in emotional intelligence. In particular, medial temporal lobe epilepsy (MTLE) is associated with disorders in emotion recognition from facial expressions. About one-third of patients with MTLE experienced febrile seizures (FSs) during childhood. In the present study, we investigated facial emotion recognition ability in a group of 38 school-aged children with antecedent FSs and in an age- and sex-matched control group. Children with abnormal general visuoperceptual abilities were excluded. Children with FSs showed lower recognition scores versus controls in both matching (28.64 vs 33.47; p<.0001) and labeling (21.25 vs 23.03; p=.001) facial emotions. Our findings support the hypothesis that FSs can be associated during childhood with a dysfunction within the neural network subserving the processing of facial expressions of the basic emotions.


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 - Investigation of the brain networks underlying eye closure sensitivity in Jeavons syndrome and healthy subjects: an EEG-fMRI study [Abstract in Rivista]
Vaudano, Ae; Avanzini, P; Ruggieri, ; Cantalupo, G; Di Bonaventura, C; Nichelli, ; Benuzzi, F; Meletti, S.
abstract


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 - 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 - Sleep and centrotemporal spikes: Thalamic BOLD changes related to centrotemporal spikes during the wake-sleep transition [Articolo su rivista]
Mirandola, L.; Cantalupo, G.; Avanzini, P.; Pugnaghi, M.; Ruggieri, A.; Benuzzi, F.; Meletti, S.
abstract

A 13 years-old right-handed boy with centrotemporal spikes (CTS) heightened during NREM sleep and with language difficulties, underwent EEG-fMRI co-registration both during wake and sleep. Scalp EEG was recorded by means of a 32 channels MRI-compatible EEG recording system and MRI was 3T (3 sessions 10 minutes long; TR: 3 sec). EEG offline was analyzed with Brainvision software and processed with Independent Component Analysis (ICA), while EEG source-imaging analysis was conducted through sLORETA software. SPM5 was utilized for functional data. During the "wake session" 47 right CTS were recorded in 10 minutes and were associated to focal cortical signal in the sensory motor cortex: increments in fMRI BOLD signal were recorded bilaterally, while EEG-source imaging showed activation in the ipsilateral sensory-motor cortex. During the "sleep session" 191 right CTS were recorded in 20 minutes: while the EEG source-imaging analysis resulted identical to the "wake session" (activation of right sensory-motor cortex), EEG-fMRI during sleep showed a more widespread activation in a cotical-subcortical network involving thalamus bilaterally, sensory-motor cortex and perisilvian cortex bilaterally. These results confirm the importance of thalamic oscillations in the genesis of CTS. Moreover, in this single case of CTS accentuated during sleep the involvement of a neural network similar to the one previously observed in patients with ESES has been identified.


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 - 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 - The effect of generalized spike and waves discharge duration and IGE sub-syndrome on brain networks as revelaed by EEG/fMRI [Abstract in Rivista]
Pugnaghi, M; Carmichael, Dw; Vaudano, Ae; Chaudhary, Uj; Benuzzi, F; DI BONAVENTURA, C; Giallonardo, At; Rodionov, R; Walker, Mc; Duncan, J; Meletti, S; Lemieux, L
abstract


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


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 - 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 - 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 - 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 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 - 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 - FACIAL EMOTION RECOGNITION IN CHILDREN WITH HISTORY OF FEBRILE SEIZURES [Abstract in Rivista]
G., Cantalupo; Meletti, Stefano; A., Miduri; S., Mazzotta; L., Rios Pohl; S., Boria; Benuzzi, Francesca; F., Pisani; C. A., Tassinari; G., Cossu
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 - HYPERFAMILIARITY FOR UNKNOWN FACES: A RARE POSTICTAL SYMPTOM OF ACUTE SYMPTOMATIC FOCAL SEIZURES [Abstract in Rivista]
R., Michelucci; P., Riguzzi; G., Rubboli; L., Volpi; Meletti, Stefano; E., Pisani; F., Santoro; F., Pittau; Benuzzi, Francesca
abstract


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 - Postictal hyperfamiliarity for unknow faces [Articolo su rivista]
R., Michelucci; P., Riguzzi; G., Rubboli; L., Volpi; E., Pasini; F., Santoro; Meletti, Stefano; Benuzzi, Francesca; F., Pittau; F., Toni; A., Marliani
abstract

Hyperfamiliarity for unknown faces (HFUF) is a rare disorder in which unfamiliar people or faces appear familiar. Three young adults were admitted for acute symptomatic secondarily generalized tonic–clonic seizures (two) and psychomotor status (one). During the days following the seizures the patients continuously experienced a strong familiarity for unknown people, including other patients, visitors, and hospital staff. This disorder disappeared gradually, lasting a mean of 13 days. Brain MRI showed left amygdalohippocampal lesions, suggesting the etiology of encephalitis in two patients and multiple “active” demyelinating lesions in one patient. Interictal and ictal EEG findings showed left temporal epileptiform abnormalities. Two patients had a transitory defect of verbal memory. HFUF is a newly defined postictal symptom, more likely to arise from left temporal epileptic discharges. In our cases it was associated with acute lesions of the temporal areas, suggesting that its occurrence may also imply a structural etiology of epilepsy.


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 - 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


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 - 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 - 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 - Neural networks related to observing symbolic and meaningless intransitive hand movements [Relazione in Atti di Convegno]
Lui, Fausta; Duzzi, Davide; Benuzzi, Francesca; M., Serafini; Baraldi, Patrizia; G., Rizzolatti; Porro, Carlo Adolfo
abstract

In spite of the increasing literature on the neural system involved in the observation of biological movements1, few studies so far have dealt with the observation of meaningful hand movements2-4. Furthermore, they yielded partially conflicting results, possibly because of different techniques used, stimuli presented and tasks assigned to the subjects. Methods Twenty healthy right-handed volunteers (8 males, 12 females; mean age 26.6) took part in this study. An event-related paradigm was adopted. A continuous video was presented, showing a table with some common objects (glasses, cup, scissors, etc.). At intervals, an actor, of whom only the trunk and arms were visible, performed different kinds of hand movements: a) symbolic (OK, hello, etc.) (SY); b) meaningless (ML); c) grasping an object; b) simply touching an object. Only data regarding the first two conditions (i.e., intransitive movements) will be presented here. No movement was ever repeated during each experiment. Three runs were carried out for each subject. Six movements for each class were shown in each run, alternated in pseudorandom order. Functional imaging was performed on a 3T Philips Intera scanner. Twenty-four axial slices were acquired (in-plane matrix: 64x64; TR: 2515 ms; voxel size: 3.75x3.75x4 mm, with a 0.6 mm gap between contiguous slices). Data analysis was carried out using SPM5. Multi-subject analyses were performed using a random effect model. In particular, direct comparisons between SY and ML, and between ML and SY, were performed. Results Direct subtraction of SY vs. ML evoked a signal increase mainly in the left hemisphere (Fig. 1, top row) in a fronto-temporal circuit including the middle temporal gyrus/superior temporal sulcus (also on the right), dorsal premotor cortex and inferior frontal gyrus; in addition, activity increased in the dorsomedial prefrontal cortex (Talairach coordinates: x=4, y=48, z=23) and in the head of the left caudate nucleus. The contrast ML vs. SY (Fig. 1, bottom row) evoked increased activity bilaterally in the middle/inferior temporal gyrus; mainly on the right in the superior and inferior parietal lobules; and exclusively on the right in premotor cortex/inferior frontal gyrus. Conclusions The present findings show that observing symbolic actions involves a mainly left fronto-temporal pathway. A focus in the dorsomedial prefrontal cortex specifically active during SY observation could be related to a circuit involved in social interactions5. Observing meaningless movements activates bilateral temporal areas and predominantly right parietal and premotor areas. Some of these latter areas are part of the mirror system1. It appears therefore that mainly the right mirror system is involved in the analysis of the motor aspects of movement, when no semantic content is present. References 1) Rizzolatti and Craighero Annu. Rev. Neurosci. 27:169-192, 2004. 2) Decety et al. Brain 120:1763-1777, 1997. 3) Tanaka et al. Neuroreport 12:1171-1174, 2001. 4) Rumiati et al. J.Cogn.Neurosci. 17:1420-1431, 2005. 5) Iacoboni et al. Neuroimage 21:1167-1173, 2004.


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.


2006 - Attributing a meaning to hand movements: an fMRI study [Relazione in Atti di Convegno]
Lui, Fausta; G., Buccino; Duzzi, Davide; Benuzzi, Francesca; Baraldi, Patrizia; Porro, Carlo Adolfo; G., Rizzolatti
abstract

Increasing attention is being paid to functional activations related to body movement inner representations, during either observation or imagery (1,2). So far, however, few studies have dealt with the presence or absence of a meaning in the observed and/or imagined movements (3).MethodsThirteen healthy right-handed volunteers (5 males, 8 females; age 20-31) took part in the study. At the beginning of each trial, a short video was presented, showing different kinds of intransitive hand movements: pantomimes, or symbolic gestures, or nonsense movements. The subjects had either to imagine to perform the same movement they had just seen in the previous video (imagery task); or to observe another movement, different from the previous one (observation task). Four runs, twenty trials each, were carried out for each subject. Functional imaging was performed on a 1.5 Signa GE MR scanner, acquiring 18 contiguous axial slices (TR: 2000 ms; voxel size: 3.75x3.75x6 mm). Data analysis was carried out using the SPM99 package (Wellcome Department of Imaging Neuroscience, London, UK). Multi-subject analyses were performed using a random effect model. In particular, in order to identify patterns of activation related to the attribution of a meaning to movements, we performed a conjunction analysis of the contrasts “pantomimes vs. nonsense” and “symbolic vs. nonsense”, for observation and imagery separately.ResultsDuring the observation of meaningful actions, as compared with meaningless movements, mainly left hemisphere activations (Fig. 1A) were found in the frontal and temporal cortex: namely, in precentral gyrus (BA 6), inferior frontal gyrus (IFG, BA45) and middle frontal gyrus (BA10), and in superior temporal gyrus (BA22); in addition, activity increased in the right middle temporal gyrus and in medial occipital areas bilaterally. During imagery of meaningful vs. meaningless movements, regions of increased signal were in the left IFG (BA45) (Fig 1B), in the right parietal operculum/posterior insula, and in lateral occipital/posterior temporal cortex in both hemispheres.ConclusionsA common region functionally activated during both imagery and observation of meaningful vs. meaningless movements is the left IFG. Actually, a smaller signal increase was present in IFG also for meaningless movements (data not shown). The IFG had been found active in a previous study when observing meaningful upper limb movements with the intention to either recognize or to imitate them (3). The IFG is part of the so-called mirror system, devoted to action understanding and imitation (1). Our results support the hypothesis that the left IFG is specifically involved in attributing a meaning to upper limb movements, during both passive (observation) and active (imagery) inner representations. 1) G. Rizzolatti and L. Craighero Annu.Rev.Neurosci. 2004.2) M. Jeannerod Neuroimage. 14:S103-S109, 2001.3) J. Decety et al. Brain 120:1763-1777, 1997.


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.


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 - 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.


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 - 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 - Neural circuits involved in the recognition of actions performed by nonconspecifics: An fMRI study [Articolo su rivista]
G., Buccino; Lui, Fausta; N., Canessa; I., Patteri; G., Lagravinese; Benuzzi, Francesca; Porro, Carlo Adolfo; G., Rizzolatti
abstract

Functional magnetic resonance imaging was used to assess the cortical areas active during the observation of mouth actions performed by humans and by individuals belonging to other species (monkey and dog). Two types of actions were presented: biting and oral communicative actions (speech reading, lip-smacking, barking). As a control, static images of the same actions were shown. Observation of biting, regardless of the species of the individual performing the action, determined two activation foci (one rostral and one caudal) in the inferior parietal lobule and an activation of the pars opercularis of the inferior frontal gyrus and the adjacent ventral premotor cortex. The left rostral parietal focus (possibly BA 40) and the left premotor focus were very similar in all three conditions, while the right side foci were stronger during the observation of actions made by conspecifics. The observation of speech reading activated the left pars opercularis of the inferior frontal gyrus, the observation of lip-smacking activated a small focus in the pars opercularis bilaterally, and the observation of barking did not produce any activation in the frontal lobe. Observation of all types of mouth actions induced activation of extrastriate occipital areas. These results suggest that actions made by other individuals may be recognized through different mechanisms. Actions belonging to the motor repertoire of the observer (e.g., biting and speech reading) are mapped on the observer's motor system. Actions that do not belong to this repertoire (e.g., barking) are essentially recognized based on their visual properties. We propose that when the motor representation of the observed action is activated, the observer gains knowledge of the observed action in a “personal” perspective, while this perspective is lacking when there is no motor activation.


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 - 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 - 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 - 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.


2001 - Grasp With Hand and Mouth: A Kinematic Study on Healthy Subjects [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; M., Gangitano; S., Grimaldi
abstract

Grasp with hand and mouth: a kinematic study on healthy subjects. J Neurophysiol 86: 1685–1699, 2001. Neurons involved in grasp preparation with hand and mouth were previously recorded in the premotor cortex of monkey. The aim of the present kinematic study was to determine whether a unique planning underlies the act of grasping with hand and mouth in humans as well. In a set of four experiments, healthy subjects reached and grasped with the hand an object of different size while opening the mouth (experiments 1 and 3), or extending the other forearm (experiment 4), or the fingers of the other hand (experiment 5). In a subsequent set of three experiments, subjects grasped an object of different size with the mouth, while opening the fingers of the right hand (experiments 6–8). The initial kinematics of mouth and finger opening, but not of forearm extension, was affected by the size of the grasped object congruently with the size effect on initial grasp kinematics. This effect was due neither to visual presentation of the object, without the successive grasp motor act (experiment 2) nor to synchronism between finger and mouth opening (experiments 3, 7, and 8). In experiment 9 subjects grasped with the right hand an object of different size while pronouncing a syllable printed on the target. Mouth opening and sound production were affected by the grasped object size. The results of the present study are discussed according to the notion that in an action each motor act is prepared before the beginning of the motor sequence. Double grasp preparation can be used for successive motor acts on the same object as, for example, grasping food with the hand and ingesting it after bringing it to the mouth. We speculate that the circuits involved in double grasp preparation might have been the neural substrate where hand motor patterns used as primitive communication signs were transferred to mouth articulation system. This is in accordance with the hypothesis that Broca’s area derives phylogenetically from the monkey premotor area where hand movements are controlled.


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 influence of stimulus color on the control of reaching-grasping movements [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; L., Bertolani; M., Gangitano
abstract

This kinematic study aimed to determine whether color is a stimulus property involved in the control of reaching-grasping movements. Subjects reached and grasped a target-object, located either on the right or on the left of the subject’s midline. A distractor, placed along the subject’s midline, could be randomly presented. The colors, i.e., both chromaticity (red and green stimuli were presented) and lightness, of the target and distractor were varied in experiment 1. Only stimulus lightness and only stimulus chromaticity were varied in experiments 2 and 3, respectively. In experiment 4 subjects matched with their thumb and index finger the size of the target-stimuli presented in experiment 1. Chromaticity (experiments 1 and 3) of the target and distractor influenced grasp, but not reach. Maximal finger aperture was larger during grasping the red than the green target. Data collected in the matching task (experiment 4) confirmed a trend to overestimate the red target and to underestimate the green one. During grasp, hand shaping was influenced by distractor chromaticity when it was different from target chromaticity. Distractor lightness affected reach, but not grasp (experiments 1 and 2). Reach was slower when the distractor was lighter and arm trajectory veered away from it. The results of the present study suggest that color, that is the ensemble of chromaticity and lightness, is a stimulus property involved in the control of reaching-grasping. The different effects of target color on reach and grasp support the notion that intrinsic object properties, such as color, affect grasp more than reach. In addition, the different effects of distractor chromaticity and lightness on reach and grasp confirm that target-objects are visually extracted from surrounding cues by means of different processes, according to the required motor response.


2001 - Visual illusions and the control of children arm movements [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; L., Bertolani; M., Gangitano
abstract

The aim of the present study was to determine whether children like adults (Gentilucci M, Chieffi S, Daprati E, Saetti MC, Toni I. Visual illusion and action. Neuropsychologia 1996;34:369–76; Gentilucci M, Daprati E, Gangitano M, Toni I. Eye position tunes the contribution of allocentric and egocentric information to target localisation in human goal directed arm movements. Neurosci Lett 1997;222:123–6) are influenced by visual illusions when they transform visual information in motor command. Children and adults pointed to a shaft extremity of the Mu¨ ller-Lyer configurations, as well as to an extremity of a control configuration. Movements were executed in two experimental conditions. In the vision condition subjects saw both the stimulus and their hand before and during movement. In the no vision (memory) condition subjects saw the stimulus and their hand before, but not during movement. Movement started 5 s after vision was precluded. The Mu¨ ller-Lyer illusion affected pointing kinematics of both children and adults. As found previously (Gentilucci M, Chieffi S, Daprati E, Saetti MC, Toni I. Visual illusion and action. Neuropsychologia 1996;34:369–76; Gentilucci M, Daprati E, Gangitano M, Toni I. Eye position tunes the contribution of allocentric and egocentric information to target localisation in human goal directed arm movements. Neurosci Lett 1997;222:123–6), subjects undershot and overshot the shaft extremity of the closed and of the open configuration, respectively. The illusion effect was greater in the no vision than in the vision condition. These results show that in children like in adults the system underlying visual perception in an object-centered frame of reference and that involved in motor control functionally interact with each other. Although the processes of target localisation were the same, the transformation of target position information in a sequence of motor patterns was different in children from that in adults. Even if both children and adults lengthened duration of the deceleration phase in the vision condition, only adults shortened duration of the acceleration phase in order to maintain constant movement time (Viviani P, Schneider R. A developmental study of the relationship between geometry and kinematics in drawing movements. J Exp Psychol 1991;17:198–218). This result suggests that children are yet unable to co-ordinate temporally acceleration with deceleration phase.


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 - Impaired control of an action after supplementary motor area: a case study. [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; L., Bertolani; E., Daprati; M., Gangitano
abstract

The kinematics of the action formed by reaching±grasping an object and placing it on a second target was studied in a patient who su ered from an acute vascular left brain lesion, which a ected the Supplementary Motor Area proper (SMA-proper) (Matelli M, Luppino G. Thalamic input to mesial and superior area 6 in the macaque monkey. Journal of Comparative Neurology 1996;372:59±87, Matelli M, Luppino G, Fogassi L, Rizzolatti G. Thalamic input to inferior area 6 and area 4 in the macaque monkey. Journal of Comparative Neurology 1989;280:468±488), and in ®ve healthy control subjects. The reach kinematics of the controls was a ected by the positions of both the reaching±grasping and the placing targets (Gentilucci M, Negrotti A, Gangitano M. Planning an action. Experimental Brain Research 1997;115:116±28). In contrast, the reach kinematics of the patient was a ected only by the position of the reaching±grasping target. By comparing these results with those previously found in Parkinson's disease patients executing the same action (Gentilucci M, Negrotti A. Planning and executing an action in Parkinson's disease patients. Movement Disorders 1999;1:69±79, Gentilucci M, Negrotti A. The control of an action in Parkinson's disease. Experimental Brain Research 1999;129:269±277), we suggest that the anatomical ``motor'' circuit formed by SMA-proper (see above), Basal Ganglia (BG) and Thalamus (Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in the Neurosciences 1990;13:266±271, Hoover JE, Strick PL. Multiple output channels in the basal ganglia. Nature 1993;259:819±821) may be involved in the control of actions: SMA-proper assembles the sequence of the action, whereas BG updates its parameters and stores them.


2000 - Language and motor control [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; L., Bertolani; E., Daprati; M., Gangitano
abstract

We investigated the possible influence of automatic word reading on processes of visuo-motor transformation. Subjects reached and grasped an object on which the following Italian words were printed: “VICINO” (near) or “LONTAN” (far) on an object either near or far from the agent (experiments 1, 2); PICCOLO (small) or “GRANDE” (large) on either a small or a large object (experiment 4); and “ALTO” (high) or “BASSO” (low) on either a high or a low object (experiment 5). The kinematics of the initial phase of reaching-grasping was affected by the meaning of the printed words. Namely, subjects automatically associated the meaning of the word with the corresponding property of the object and activated a reach and/or a grasp motor program influenced by the word. No effect on initial reach kinematics was observed for words related to object properties not directly involved in reach control (experiment 3). Moreover, in all the experiments, the presented words poorly influenced perceptual judgement of object properties. In experiments 5–7, the effects of the Italian adjectives “ALTO” (high) and “BASSO” (low) on reaching-grasping control were compared with those of the Italian adverbs “SOPRA” (up) and “SOTTO” (down). Adjectives influenced visual analysis of targetobject properties, whereas adverbs more directly influenced the control of the action. We suggest that these effects resemble the structure of a sentence, where adjectives are commonly referred to nouns, and adverbs to verbs. In other words, class of words and, in a broad sense, grammar influenced motor control. The results of the present study show that cognitive functions such as language can affect visuo-motor transformation. They are discussed according to the notion that a strict relation between language and motor control exists, and that the frontal cortex can be involved in interactions between automatic word reading and visuo-motor transformation.


2000 - Recognising a hand by grasp [Articolo su rivista]
M., Gentilucci; Benuzzi, Francesca; L., Bertolani; E., Daprati; M., Gangitano
abstract

The present study aimed to demonstrate that motor representations are used to recognise biological stimuli. In three experiments subjects were required to judge laterality of hands and forearms presented by pictures. The postures of the hands were those assumed when holding a small, medium and large sphere. In experiment 1, the sphere held in hand was presented, whereas in experiment 2 it was absent. In experiment 3, the same images, showing holding-a-sphere hands, as in experiment 1 were presented, but without forearm. In all experiments one finger of each hand could be absent. In experiment 1 recognition time was longer for those hand postures for which the corresponding grasping motor acts required more accuracy. This was confirmed by a control experiment (experiment 4), in which subjects actually grasped the spheres. Absence of fingers did not influence right–left hand recognition. However, the absence of target object in experiment 2, and of forearm in experiment 3 reduced the effects of the type of holding on hand laterality recognition. The results of the present study indicate that grasp representations are used to recognise hand laterality. In particular, the visual description of how hand and object interact in space (the opposition space [M.A. Arbib, Programs, schemas and neural networks for control of hand movement: beyond the RS frameworks, in: M. Jeannerod (Ed.), Attention and Performance XIII: Motor Representation and Control, Lawrence Erlbaum, Hillsdale, NJ, 1990, 111–138; M.A. Arbib, T. Iberall, D. Lyons, Coordinated control programs for movements of the hand, in: A.W. Goodman, I. Darian-Smith (Eds.), Hand function and the neocortex, Springer, Berlin, 1985, pp. 135–170]) and the anchoring of the hand to the agent are the features of the grasp representations used in hand-recognition processes. The data are discussed according to the more general notion that motor representations are automatically extracted in the process of intuiting situations, or people's intentions. These motor representations, which are compared with those of other people, contain concrete information on the actions (the motor program) by which a situation is created and on the aim of the agents executing those actions.