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Fausta LUI

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

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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.

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.

2021 - Changes in Cancer Patients' and Caregivers' Disease Perceptions While Receiving Early Palliative Care: A Qualitative and Quantitative Analysis [Articolo su rivista]
Borelli, Eleonora; Bigi, Sarah; Potenza, Leonardo; Eliardo, Sonia; Artioli, Fabrizio; Mucciarini, Claudia; Cottafavi, Luca; Cagossi, Katia; Razzini, Giorgia; Cruciani, Massimiliano; Pietramaggiori, Alessandra; Fantuzzi, Valeria; Lombardo, Laura; Ferrari, Umberto; Ganfi, Vittorio; Lui, Fausta; Odejide, Oreofe; Cacciari, Cristina; Porro, Carlo Adolfo; Zimmermann, Camilla; Efficace, Fabio; Bruera, Eduardo; Luppi, Mario; Bandieri, Elena

2021 - Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals [Articolo su rivista]
Borelli, Eleonora; Bigi, Sarah; Potenza, Leonardo; Artioli, Fabrizio; Eliardo, Sonia; Mucciarini, Claudia; Cagossi, Katia; Razzini, Giorgia; Pasqualini, Antonella; Lui, Fausta; Ferlazzo, Fabio; Cruciani, Massimiliano; Bruera, Eduardo; Efficace, Fabio; Luppi, Mario; Cacciari, Cristina; Porro, Carlo Adolfo; Bandieri, Elena

2021 - Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data [Articolo su rivista]
Zunhammer, M.; Spisak, T.; Wager, T. D.; Bingel, U.; Atlas, L.; Benedetti, F.; Buchel, C.; Choi, J. C.; Colloca, L.; Duzzi, D.; Eippert, F.; Ellingsen, D. -M.; Elsenbruch, S.; Geuter, S.; Kaptchuk, T. J.; Kessner, S. S.; Kirsch, I.; Kong, J.; Lamm, C.; Leknes, S.; Lui, F.; Mullner-Huber, A.; Porro, C. A.; Rutgen, M.; Schenk, L. A.; Schmid, J.; Theysohn, N.; Tracey, I.; Wrobel, N.; Zeidan, F.

The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We find that placebo vs. control treatments induce small, widespread reductions in pain-related activity, particularly in regions belonging to ventral attention (including mid-insula) and somatomotor networks (including posterior insula). Behavioral placebo analgesia correlates with reduced pain-related activity in these networks and the thalamus, habenula, mid-cingulate, and supplementary motor area. Placebo-associated activity increases occur mainly in frontoparietal regions, with high between-study heterogeneity. We conclude that placebo treatments affect pain-related activity in multiple brain areas, which may reflect changes in nociception and/or other affective and decision-making processes surrounding pain. Between-study heterogeneity suggests that placebo analgesia is a multi-faceted phenomenon involving multiple cerebral mechanisms that differ across studies.

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

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

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

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.

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

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

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

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.

2018 - Placebo Effects on the Neurologic Pain Signature: A Meta-analysis of Individual Participant Functional Magnetic Resonance Imaging Data [Articolo su rivista]
Zunhammer, Matthias; Bingel, Ulrike; Wager, Tor D; Porro, Carlo Adolfo; Lui, Fausta.

Importance: Placebo effects reduce pain and contribute to clinical analgesia, but after decades of research, it remains unclear whether placebo treatments mainly affect nociceptive processes or other processes associated with pain evaluation. Objective: We conducted a systematic, participant-level meta-analysis to test the effect of placebo treatments on pain-associated functional neuroimaging responses in the neurologic pain signature (NPS), a multivariate brain pattern tracking nociceptive pain. Data Sources: Medline (PubMed) was searched from inception to May 2015; the search was augmented with results from previous meta-analyses and expert recommendations. Study Selection: Eligible studies were original investigations that were published in English in peer-reviewed journals and that involved functional neuroimaging of the human brain with evoked pain delivered under stimulus intensity-matched placebo and control conditions. The authors of all eligible studies were contacted and asked to provide single-participant data. Data Extraction and Synthesis: Data were collected between December 2015 and November 2017 following the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. Results were summarized across participants and studies in a random-effects model. Main Outcomes and Measures: The main, a priori outcome was NPS response; pain reports were assessed as a secondary outcome. Results: We obtained data from 20 of 28 identified eligible studies, resulting in a total sample size of 603 healthy individuals. The NPS responses to painful stimulation compared with baseline conditions were positive in 575 participants (95.4%), with a very large effect size (g = 2.30 [95% CI, 1.92 to 2.69]), confirming its sensitivity to nociceptive pain in this sample. Placebo treatments showed significant behavioral outcomes on pain ratings in 17 of 20 studies (85%) and in the combined sample (g = -0.66 [95% CI, -0.80 to -0.53]). However, placebo effects on the NPS response were significant in only 3 of 20 studies (15%) and were very small in the combined sample (g = -0.08 [95% CI, -0.15 to -0.01]). Similarly, analyses restricted to studies with low risk of bias (g = -0.07 [95% CI, -0.15 to 0.00]) indicated very small effects, and analyses of just placebo responders (g = -0.22 [95% CI, -0.34 to -0.11]) indicated small effects, as well. Conclusions and Relevance: Placebo treatments have moderate analgesic effects on pain reports. The very small effects on NPS, a validated measure that tracks levels of nociceptive pain, indicate that placebo treatments affect pain via brain mechanisms largely independent of effects on bottom-up nociceptive processing.

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

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.

2014 - Ranking brain areas encoding the perceived level of pain from fMRI data [Articolo su rivista]
S., Favilla; A., Huber; Pagnoni, Giuseppe; Lui, Fausta; P., Facchina; Cocchi, Marina; Baraldi, Patrizia; Porro, Carlo Adolfo

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study,we aimed to identify themore relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus.Most of these regions, with the exception of medial thalamus,were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in amodel of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception

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

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 - Spatial extent of pain influences gray matter volume in fibromyalgia patients. [Poster]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Santarcangelo, E. L.; Carli, G.; Porro, Carlo Adolfo

Aim of Investigation: Fibromyalgia (FS) is a syndrome characterised by chronic widespread pain, whose pathophysiology is still controversial. Previous studies assessing alterations in local gray matter volume (GMV) in FS have obtained somewhat inconsistent results, possibly due to differences in clinical features. Our aim was to assess GMV changes in FS compared to a control group, and their correlations with the severity of clinical aspects, including illness duration, pain intensity and quality, body pain area, number of positive tender points and depression. Methods: Thirty-four women with FS diagnosed by a rheumatologist and 38 healthy women (controls, C) without chronic pain matched for age (FS: range 18-55 ys, mean 44; C: 25-60 ys, mean 45.6), menopausal status, educational level, handedness and caffeine consumption, participated in the study. The control subjects had experienced no pain (N=9) or episodic/recurrent pain without (N=20) or with use of pain killers (N=9) over the past year. Depressive symptoms were assessed using the Center for Epidemiology Studies-Depression Scale (CES-D); the sensory (S), affective (A) and evaluative (E) quality of spontaneous pain were tested using the Italian adaptation of the McGill Pain Questionnaire (Questionario Italiano del Dolore - QUID). Spatial extent of pain was assessed using Margolis body pain area drawings. Pressure pain thresholds were measured by means of an algometer applied to the 18 defining tender points and to 10 additional points to obtain a detailed picture of spatial distribution of allodynia. A high-resolution structural T1-weighted brain scan (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50; TE 5.7ms) was acquired for each subject, using a 3T Philips Achieva MR scanner. GMV was assessed applying voxel-based morphometry Oasis, The Online Abstract Submission System 1 of 3 03/07/2014 01:46 PM International Association for the Study of Pain 1510 H Street NW, Suite 600 Washington, DC 20005-1020 USA Phone: +1-202-524-5300 (VBM) to modulated data in SPM8 using the VBM8 toolbox (voxel-wise critical p < 0.005; cluster size corrected for multiple comparisons using AlphaSim with 10,000 Monte Carlo simulations). Results: Patients showed no significant differences in GMV compared to the total control group. In the patient sample, GMV was negatively correlated with QUID-E score in BA 6 and with the spatial extent of spontaneous pain in the bilateral parahippocampal gyrus (pHG), and it was positively correlated with illness duration in the cerebellum. GMV was independent of pain intensity, tender point count, CES-D, QUID-S and QUID-A score. Reported pain extent ranged from 9-90% of body surface (mean/median: 48%). Patients with below-median pain extent had greater GMV than patients with above-median values in the bilateral pHG and cerebellum, left paracentral lobule (BA 6) and cingulate gyrus (BA 31). GMV values of the controls in these brain areas were intermediate between the two patient groups. Spatial extent of pain was positively correlated with tender point count and with QUID-S and was independent of all other clinical and nuisance variables included in the study. Conclusions: Some, but not all, previous VBM studies have reported reduced GMV in the pHG and in the cingulate cortex in FS (Wood, 2010). Our results point to a possible explanation for these inconsistent findings: depending on how widespread their pain, FS patients may show either reduced or increased GMV in the pHG and cingulate cortex, i.e. they are more different from each other than from the control group. Further research is needed to explore the possible causes of these inter-individual differences within the FS population. Reference: Wood PB. Variations in brain gray matter associated with chronic pain. Curr Rheumatol Rep 2010;12:462-469.

2014 - Structural and functional cerebral correlates of hypnotic suggestibility [Articolo su rivista]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

2014 - Whole-Body Mapping of Spatial Acuity for Pain and Touch [Articolo su rivista]
Flavia, Mancini; Bauleo, Armando; Jonathan, Cole; Lui, Fausta; Porro, Carlo Adolfo; Patrick, Haggard; Gian Domenico, Iannetti

Objective: Tactile spatial acuity is routinely tested in neurology to assess the state of the dorsal column system. In contrast, spatial acuity for pain is not assessed, having never been systematically characterized. More than a century after the initial description of tactile acuity across the body, we provide the first systematic whole-body mapping of spatial acuity for pain. Methods: We evaluated the 2-point discrimination thresholds for both nociceptive-selective and tactile stimuli across several skin regions. Thresholds were estimated using pairs of simultaneous stimuli, and also using successive stimuli. Results and interpretation: These two approaches produced convergent results. The fingertip was the area of highest spatial acuity, for both pain and touch. On the glabrous skin of the hand, the gradient of spatial acuity for pain followed that observed for touch. On the hairy skin of the upper limb, spatial acuity for pain and touch followed opposite proximal–distal gradients, consistent with the known innervation density of this body territory. Finally, by testing spatial acuity for pain in a rare participant completely lacking Ab fibers, we demonstrate that spatial acuity for pain does not rely on a functioning system of tactile primary afferents. This study represents the first systematic characterization of spatial acuity for pain across multiple regions of the body surface.

2013 - Comparison of tissue occupancy functional contrasts for 3D turbo-spin-echo acquisition [Poster]
Summers, Paul Eugene; Bauleo, Armando; Cretti, F.; Lui, Fausta; Porro, Carlo Adolfo

Introduction: Functional vascular occupancy imaging has demonstrated task correlated MR signal changes using inversion recovery (IR) prepared images, where the inversion time (TI) has been chosen to selectively null blood (vascular space occupancy – VASO, (Lu et al., 2003)), grey matter (VASO by tissue suppression – VAST (Wu et al., 2008)), or CSF (VASO-FLAIR (Donahue et al., 2006)). Weakness of these approaches are that functional responses may not be due to volume changes in a single tissue compartment, and that the underlying imaging sequence may be sensitive to other mechanisms (e.g. BOLD) (Donahue et al., 2006). Our purpose was to compare the functional responses from different vascular space occupancy preparations of a short TE turbo-spin echo (TSE) sequence. Methods: Eight healthy subjects were scanned at 3T after providing informed consent. The task consisted of self-paced, left-hand finger tapping. Four variants of vascular occupancy fMRI were tested: VASO (TI = 646ms), VAST (TI = 578ms), VASO-FLAIR (TI = 781ms) and nonInVASO (no inversion pulse VASO), all based on a 3D TSE acquisition (TE/TR 8.4ms/2.4s, 4 shots, time per volume 9.6s, 1.5x1.5x1.5mm, 8 slices, FOV 222x60x12mm, 180° refocusing pulses, ant/post sat bands). Task blocks were 48s long, and each run consisted of 45 volumes, with the sequence order varied between subjects. These scans were centered on the focus of BOLD response in/adjacent to the right hand knob detected with an EPI acquisition (TE/TR 30ms/3s, 3x3x3mm, 42 slices) performed during execution of the same task (30 second blocks, 70 volumes). Whole-brain T2, 3D T1, and nonInVASO images were also obtained. GLM analysis (1.5mm FWHM smoothing, high pass filter cut-off 100s, default gamma-variate hrf, GRF-based voxel-wise corrected p<0.05) was per formed following motion correction and ICA denoising (4 components) using fsl (v 5.0.1). Due to slight rotations during acquisition, only 6 slices were retained for analysis. Results: Despite operator confirmation of task performance, one subject showed minimal BOLD and no significant vascular occupancy responses, and was therefore excluded from analysis. In the other subjects, VASO, VAST and VASO-FLAIR showed nearly identical patterns and locations of activity (Figure 1) and no significant differences in the grey matter (GM), white matter, CSF distribution of activated voxels. The nonInVASO scans showed smaller volumes of activity. GM was the predominant site of response for all scans. VAST yielded the highest % signal changes; VASO yielded the highest z-score followed closely by VASO-FLAIR; and these all had signal changes negatively correlated with the task. The nonInVASO responses correlated positively with the task and were the smallest % signal change and maximum z-scores roughly one-third lower than VASO. Significant oppositely-signed responses (i.e. positive of VASO, VAST and VASO-FLAIR, negative for nonInVASO) were not observed.Conclusions: Our results suggest that VASO, VAST and VASO-FLAIR are sensitive to volume changes in the same tissue compartment. VAST yielded the highest % signal changes due mainly to the smallest baseline signal but this did not result in greater sensitivity to activation as indicated by maximum z-scores. The negative VAST response however, suggests that the inversion was not fully optimized to grey matter but could reflect T2 blurring of white matter signal. VASO was the most sensitive to activation followed closely by VASO-FLAIR. Similarly located activations were seen with nonInVASO, but with smaller spatial extents and lower sensitivity. The implications and operative mechanism for the nonInVASO functional contrast remain to be established. Possible mechanisms include BOLD contrast (through T2 sensitivity or blurring by the long TSE echo train), vascular space occupancy changes coupled with inherent blood-tissue contrast, diff

2013 - Hypnotic susceptibility explains differences in resting state functional connectivity [Poster]
Huber, Alexa; Lui, Fausta; Pagnoni, Giuseppe; Duzzi, Davide; Summers, Paul Eugene; Porro, Carlo Adolfo

Introduction: Hypnotic susceptibility (HS) is a measurable cognitive trait defined as the generalized tendency to respond to hypnotic suggestions [1]. Very little is known about the neural bases of HS [2]. Our aim was to assess HS-related differences in resting state func tional c onnec tivity. Methods: N=35 healthy women (3 ambidextrous, 4 left-handed; age range 19-56 yrs, mean 36.9 yrs) partic ipated in the study. HS was assessed with the Stanford Hypnotic Susc eptibility Sc ale – Form A (SHSS:A), mental absorption with the T ellegen Absorption Sc ale (T AS) and trait anxiety with the State-T rait Anxiety Inventory Form Y (ST AI-Y2). Subjec ts were not in any way pre-selec ted for SHSS sc ore. T o measure spontaneous BOLD signal fluc tuations at rest, two runs of EPI sc ans were ac quired while subjec ts lay in the sc anner relaxed with eyes c losed (for eac h run: 200 volumes; T R 2 s; isometric voxel size 3.6 mm; 35 axial slic es without gap; matrix 80 x 63 voxels; FOV 286 x 229 mm; ac quisition time 7 min), using a 3T Philips Ac hieva MR sc anner. A T 1-weighted brain image (isotropic voxel size 0.5 mm) was ac quired for inter-subjec t alignment. EPI data were analysed using AFNI. Preproc essing inc luded the removal of physiologic al, white matter and hardware related noise using RET ROICOR and ANAT ICOR proc edures, lowpass filtering to remove frequenc ies >0.1 Hz, and 6-mm FWHM spatial smoothing. Seed-based func tional c onnec tivity (FC) was quantified as the z-transformed Pearson c orrelation with the seed signal (average BOLD signal within a sphere of 6mm radius). Seeds were plac ed (a) within key regions of the Default Mode Network (DMN) taken from the literature; (b) in the two areas (anterior c ingulate c ortex – ACC; dorsolateral prefrontal c ortex – DLPFC) desc ribed in Hoeft et al. [2]; and (c ) in 15 seeds ad-hoc plac ed along the c ingulate c ortex in eac h hemisphere. HS-related differenc es in FC were assessed by using SHSS sc ore as a between-subjec ts linear regressor to explain FC z-sc ores. Furthermore, some of the c lusters whic h resulted signific antly c onnec ted with the above mentioned seeds, e.g. orbitofrontal c ortex (OFC), were, in turn, used as seeds (d). Results: SHSS sc ores ranged from 0-10 (mean 3.6). Eighteen subjec ts had low (SHSS<4), 14 medium (SHSS=4-7) and 3 high SHSS sc ores (SHSS>7). SHSS was independent of age, educ ational level, handedness, trait anxiety and mental absorption. SHSS was positively c orrelated with FC (a) of DMN seeds, i.e., the right medial PFC, left posterior c ingulate c ortex (PCC) and left posterior insula with c erebellar foc i, and (b) of Hoeft et al.'s [2] ACC seed with c erebellar regions, and of right DLPFC with left OFC. When foc using on the c ingulate c ortex (c ), SHSS was positively c orrelated with FC of ACC with mid-c ingulate c ortex (MCC), of various seeds in the ACC and MCC with c erebellar foc i, and of MCC with bilateral OFC. SHSS was also positively c orrelated with FC of the OFC foc i (d) with a wide network of regions, inc luding MCC, bilateral DLPFC (see Fig. 1), pre- and postcentral gyri, superior temporal gyri and insula as well as cerebellum and contralateral precuneus (Fig. 2). Conclusions:Among healthy women, individuals with higher HS show higher resting state FC between OFC, DLPFC, cingulate cortex and cerebellum. Further researc h is needed to c onfirm these relationships in men, and to assess their cognitive correlates.

2013 - Hypnotic susceptibility modulates brain activity related to experimental placebo analgesia [Articolo su rivista]
Huber, Alexa; Lui, Fausta; Porro, Carlo Adolfo

Identifying personality traits and neural signatures that predict placebo responsiveness is important, both on theoretical and practical grounds. In the present functional magnetic resonance imaging (fMRI) study, we performed multiple-regression interaction analysis to investigate whether hypnotic susceptibility (HS), a cognitive trait referring to the responsiveness to suggestions, explains interindividual differences in the neural mechanisms related to conditioned placebo analgesia in healthy volunteers. HS was not related to the overall strength of placebo analgesia. However, we found several HS-related differences in the patterns of fMRI activity and seed-based functional connectivity that accompanied placebo analgesia. Specifically, in subjects with higher HS, the placebo response was related to increased anticipatory activity in a right dorsolateral prefrontal cortex focus, and to reduced functional connectivity of that focus with brain regions related to emotional and evaluative pain processing (anterior mid-cingulate cortex/medial prefrontal cortex); an opposite pattern of fMRI activity and functional connectivity was found in subjects with lower HS. During pain perception, activity in the regions reflecting attention/arousal (bilateral anterior thalamus/left caudate) and self-related processing (left precuneus and bilateral posterior temporal foci) was negatively related to the strength of the analgesic placebo response in subjects with higher HS, but not in subjects with lower HS. These findings highlight HS influences on brain circuits related to the placebo analgesic effects. More generally, they demonstrate that different neural mechanisms can be involved in placebo responsiveness, depending on individual cognitive traits.

2013 - Short echo-time 3D-TSE with and without VASO preparation: functional MRI [Poster]
Summers, Paul Eugene; Bauleo, Armando; Cretti, Fabiola; Lui, Fausta; Porro, Carlo Adolfo

Purpose: Short echo time (shTE) turbo-spin echo (TSE) pulse sequences are considered very weakly sensitive to blood oxygenation level dependent (BOLD) signal changes, and have been proposed to avoid cancellation of functional responses in blood nulled vascular space occupancy (VASO) fMRI studies where task-related increases in blood volume lead to decreases in signal (1,2). A positive functional contrast in shTE TSE studies has, however, been reported by some authors and attributed to changes in extravascular water distribution termed SEEP (3). Our purpose was to determine whether functional contrast in shTE TSE-based VASO experiments might be contaminated by BOLD or SEEP effects. Methods: A 3D-TSE sequence without (shTE TSE; TE/TR/TDyn 8.5ms/2400ms/9.6s, FOV: 210x52x12mm, Matrix 160x40x8, Refocussing Angle 180deg, Turbo factor 80, echo spacing 8.5ms, 70 dynamics, centre-out sampling) and with blood-nulling (VASO; TI 600ms) was used to acquire image series from the hand sensorimotor area of the cerebral cortex during a block-design finger tapping task (block duration 48s, 9 blocks). The inversion time assumed suppression of longitudinal relaxation during the TSEecho train. For comparison purposes, a BOLD-sensitive gradient-echo EPI series was also obtained (TE/TR/TDyn 35ms/3000ms/3s, FOV: 230x230x120, Matrix 64x64x30, Excitation Flip Angle 90deg, 70 dynamics) with the same task. The finger tapping task was self-paced left-hand finger tapping, and controlled via auditory commands. fMRI time-series were motion-corrected, and an independent component analysis (MELODIC, fsl) used to identify 7 components for denoising prior to a glm (FEAT, fsl) with a single regressor convolved with the default hemodynamic response function. Spatial smoothing was limited to a 1.5mm FWHM. Voxels were considered to show a significant functional response using a p-value < 0.005 with cluster-wise correction for multiple comparisons. We present results from the first 2 subjects who participated in the study. Results: Functional responses were found using both variants of the shTE TSE sequence within the area of BOLD response seen with conventional EPI-based fMRI. The spatial correspondence of responses was striking (Figures 1a and 1b), but having an inverted response when blood-nulling is applied (Figure 1c; bars indicate task blocks). The sequences yielded similar maximum functional contrast to noise ratios of 4.0 and 4.6 (on % signal changes of 0.98% and 3.6%) without and with blood-nulling respectively. Discussion: The inverted functional response when blood-nulling is applied indicates the expected VASO changes. The robust functional contrast in shTE TSE without blood nulling may also be consistent with this effect, but our results are not sufficient to exclude contributions from SEEP, or BOLD that would run counter to the VASO contrast in blood-nulled measurements. The functional contrast to noise ratio in both cases are similar. Nonetheless, the small fractional signal change in the non-nulled case suggests that BOLD and SEEP and inflow effects make only minor contributions. The 3D TSE strategy used here is hampered by limited spatial coverage and low temporal efficiency relative to conventional EPI. Improvements are likely possible however, as we have not made use of parallel imaging techniques, nor pursued extremely long echo trains that may reduce scan time. References: 1. Stroman P, et al. Magnetic Resonance in Medicine 49:433–439 (2003). 2. Cretti F, et al. ESMRMB 2009 187. 3. Poser B, Norris D. Magn Reson Mater Phy (2007) 20:63–67.

2013 - The spatial resolution of the nociceptive system. [Poster]
Bauleo, Armando; Mancini, F.; Lui, Fausta; Porro, Carlo Adolfo; Haggard, P.

Background and aims: A systematic study of the spatial resolution of the nociceptive system across different body districts is surprisingly lacking, especially considering the recent description of a fovea for pain at the fingertips (Mancini et al Curr Biol 2013). In this psychophysical study we assessed the spatial acuity of ten body regions, using the two-point discrimination (2PD) of Nd:YAP laser pulses that selectively activate Aδ cutaneous afferents. Methods: Using two Nd:YAP lasers we delivered either one or two simultaneous pulses (diameter: 1.3 mm) of identical energy on each of the following body sites: forehead, volar forearm, hand dorsum, hand palm, fingertip, shoulder, lower back, upper thigh, calf, and foot dorsum. The 2PD task consisted in judging whether one or two stimuli were delivered, using ascending and descending staircases of varying spatial distance between the two pulses. Single stimuli were included as catch trials. All stimuli elicited a clear pinprick sensation related to the activation of Aδ afferents. Results: We found a proximal-distal gradient of spatial acuity for nociceptive stimuli, with higher acuity for proximal stimuli, an observation in agreement with innervation density of skin nociceptors and perceptual threshold of Aδ stimuli. Two distal regions (fingertips and palm) represented an exception, and showed maximal spatial acuity (see also Mancini et al., 2013). Conclusions: This study provides the first systematic description of spatial acuity of the nociceptive system across the entire body in healthy participants.

2012 - Alterations in cortical gray matter volume, thickness and surface area in women with fibromyalgia syndrome. [Poster]
Lui, Fausta; Huber, Alexa; Duzzi, Davide; Summers, Paul Eugene; Porro, Carlo Adolfo

Aim of Investigation: Recent neuroimaging studies using voxel-based morphometry (VBM) demonstrated reductions in brain gray matter (GM) volume in Fibromyalgia (FS), a chronic pain syndrome thought to result from altered central pain processing. Little is known about the relative contribution of the two components of cortical GM volume – thickness and surface area – to these structural alterations. Our aim was to assess alterations in GM morphology (volume, thickness, area) in FS compared to a control group, and to correlate GM morphology with clinical variables of pain, namely duration, intensity (VAS), and tender point count, and with depression score (Center for Epidemiology Studies-Depression Scale). Methods: Twenty-three women with FS and 26 healthy pain-free women matched for age and educational level participated in the study. Pressure pain thresholds were measured with an algometer applied to the 18 defining tender points and to 10 additional points to obtain a total positive tender point count. A high-resolution structural T1-weighted brain scan (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50°; TE 5.7ms) was acquired for each subject, using a 3T Philips Achieva MR scanner. GM volume was assessed applying VBM to modulated data in SPM8 using an individualised DARTEL template for inter-subject alignment. Surface-based measures of cortical thickness and area were obtained using the Freesurfer 4.5.0 software. Both the VBM and Freesurfer data were spatially smoothed using an 8mm FWHM Gaussian kernel. The statistical analysis of the surface-based data was performed both on vertex-wise values and on values averaged within 64 anatomical Regions of Interest (ROIs). Nuisance influences of age, total intracranial volume (TIV), handedness and menopause were removed. Results: Compared to the control group, FS patients showed i) reduced GM volume in the left medial and superior frontal gyrus (BA 6; a trend that became significant after controlling for depression score), ii) reduced surface area in the left pericalcarine cortex, and iii) increased thickness in the left fusiform gyrus and in the right rostral middle frontal cortex. Pain intensity was negatively correlated with thickness in the bilateral paracentral lobule (BA 6); however, brain morphology was correlated neither with pain duration nor with positive tender point count. The only significant age-by-group interaction consisted in the fact that the age-related loss in GM thickness and area in the left lateral occipital cortex was less steep in patients compared to controls, because the patients had lower values already at a younger age. Conclusions: The present results provide further evidence for altered brain morphology in FS, including brain areas in which this had not been previously demonstrated, and show a relationship of specific structural changes with the severity of specific symptoms.

2012 - Psychological and brain structural correlates of responsiveness to analgesia suggestions in patients with fibromialgia syndrome. [Poster]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Summers, Paul Eugene; Carli, G.; Santarcangelo, E. L.; Porro, Carlo Adolfo

Aim of Investigation: In healthy people, the effectiveness of analgesia suggestions increases with the individual level of hypnotic susceptibility (HS), a measurable cognitive trait defined as the generalized tendency to respond to hypnotic suggestions. However, chronic pain patients may benefit from analgesia suggestions even when they are low susceptible to hypnosis. Very little is known about the potential brain structural correlates of the responsiveness to analgesia suggestions in chronic pain. Our aim was to assess possible a) psychological and b) gray matter (GM) morphology correlates of inter-individual differences in the patients' behavioural response to an imaginative analgesia suggestion, in women suffering from chronic pain due to fibromyalgia syndrome (FS), using MRI. Methods: Sixty-eight women with FS and 26 healthy women participated in a screening session to fill in questionnaires on depression (CES-D), anxiety (STAI-Y), mental absorption (TAS), imagery ability (BETTS) and (for the patients) on clinical symptoms and pain coping strategies (BPCI). HS was assessed with the Stanford Hypnotic Susceptibility Scale (SHSS:A). A 1.5-min imaginative analgesia suggestion was read once to each patient during normal waking (i.e., without a hypnotic induction) without any prior training. A high-resolution structural T1-weighted brain image (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50°; TE 5.7ms) was acquired for 23 of the patients and all 26 controls, using a 3T Philips Achieva MR scanner. GM volume was assessed applying VBM to modulated data in SPM8, using a tailored DARTEL template for inter-subject alignment. Surface-based measures of cortical thickness and surface area were obtained using the Freesurfer 4.5.0 software. Nuisance influences of age, total intracranial volume, handedness and educational level were removed in the analysis. Results: Patients and controls showed similar HS levels (mean±SD: all patients 4.7±3.0; scanned patients 4.0±3.0; controls: 2.9±2.7). Behavioural data showed that the majority (76%) of patients reported reduction of ongoing pain, either weak-moderate (1-30%; n=20) or strong (>30%; n=32), following the analgesia suggestion reading; a similar proportion was found in patients who underwent scanning. The amount of analgesia was positively correlated with HS (Pearson r=.48), mental absorption (r=.31) and mental avoidance coping (r=.25), and negatively with state anxiety (r=-.41), support-seeking coping (r=-.27) and opioid use; it was independent of all other clinical variables, including pain intensity and duration. While controlling for HS, the amount of analgesia was negatively trend correlated with GM volume in the anterior midbrain/hypothalamus (this cluster missed significance by 11 voxels). In the control sample (but not in the patient sample), higher HS was associated with reduced GM volume in the posterior insula bilaterally. Across the whole scanned group (subjects and patients), HS was associated with reduced cortical thickness in the left medial orbitofrontal cortex. Conclusions: This is the first study to demonstrate a relationship of brain GM anatomical features with HS and the effectiveness of cognitive modulation of clinical pain induced by analgesia suggestions in the waking state. A larger cohort of patients including a higher number of highly hypnotisable individuals is needed to investigate these relationships more thoroughly.

2012 - The role of phase-of-firing coding in global synchronizations among distant primary cortices. [Poster]
Gelsomino, G; Zippo, A. G.; Nencini, S.; Valente, M.; Lui, Fausta; Biella, G. E. M.

Cognition and behavior are the consequence of sophistlcated lnteractions among different neuronal groups in the nervous system. A global communicalion model proposed in recent years, a.k.a. neuronal avalanche model, ca explain some powerful property, by the analysis of sèikes and local field potentials (LFPs). As preliminary result, we found that, during spontaneous and stimulus-evoked activities, the distributions of spike preferre LFP phases, from configurations with global synchronizations, are significantly different than the distributions from those without global synchronizations.

2012 - “To accept or to reject? It depends on who proposes it”. An fMRI study on the Ultimatum Game. [Poster]
Lui, Fausta; Bauleo, Armando; Pesciarelli, Francesca; Duzzi, Davide; Lotto, L; Cacciari, Cristina; Rumiati, R; Porro, Carlo Adolfo

Introduction: In the Ultimatum Game (UG), a proposer decides in which proportion to split a fixed amount of money (e.g., 10 €) with a responder. Both get their share only if the responder accepts the offer. Despite what would be predicted by expected utility models, typically some offers (most frequently the lowest ones) are rejected, being considered unfair [3]. Brain imaging and TMS studies [2, 4-5, 7] have investigated the brain circuits involved in different aspects of the UG. In the present study, we tested the hypothesis that the identity of the proposers, specifically, their economic status, i) affects acceptance rates; ii) modulates brain activity of the responders in the UG protocol. Methods: Twenty-one healthy right-handed volunteers (all females; mean age 22.8 ± 3.1) took part in this study. During the fMRI scan, each volunteer was asked to play 54 trials (split in 3 runs) of UG. All human proposers were presented as females and could be either A) old-age retirees living on a small pension, or B) well-to-do businesswomen/professionals. Their identity was introduced by a brief description including first name, age and social status (e.g., Maria, 84, with minimum pension). Offers by a computer were the control condition. The amount of money to share was € 10 in each trial, with three types of offers. that we defined as: Unfair (1 or 2 €), Fair (4 or 5 €), Mid-value (3 €). On each trial, participants saw the description of the proposer (8 s), then they were presented with an offer (8 s). Both proposer and offer type were presented in random order. Finally, participants accepted or rejected the offer by pressing a button. Functional imaging was performed on a 3T Philips Achieva scanner. Thirty axial slices were acquired (TR=2000 ms; FOV=240x240 mm; in-plane matrix=80x80; voxel size=3.0x3.0x4.0 mm). Data analysis was carried out using a General Linear Model (GLM) as implemented in SPM5; significance level was set at α < 0.05 corrected for multiple comparisons, as assessed by AlphaSim ( Results: Behavioral data: Acceptance rates were significantly higher for proposer A than for the other proposers, for both Unfair and Mid-value offers (p<0.001), but not for Fair offers. fMRI data: Unfair offers, compared to Fair offers, elicited signal increases in anterior mid-cingulate cortex (aMCC) and right prefrontal cortex (PFC); smaller (subthreshold) clusters were present also in left PFC and, bilaterally, in anterior insula (Fig.1). The contrast Fair vs. Unfair offers did not elicit suprathreshold activity. When we compared proposer B vs A in the trials in which offers were subsequently accepted, we found a significant signal increase in the right insula (Fig. 2). When offers were subsequently rejected, a comparison of proposer A vs B revealed an active cluster in precuneus/posterior cingulate cortex (PCC) (Fig. 3). The opposite contrasts did not reveal any significant cluster. Conclusions: We show here that the economic status of the proposers selectively affects i) acceptance rates, and ii) brain activity; namely, in case of accepted offers, proposer B caused a selective activation in posterior insula. This area is known to have complex functions, among which a role in pain perception and modulation [6] and in attention to negative emotions [8]. This activation might suggest that accepting the offers from proposer B bears some similarity with an unpleasant experience. In case of subsequently rejected offers, proposer A caused a selective activation in precuneus/PCC. This is a very complex region, part of the so-called "default mode network", which is active during the conscious resting state, and inhibited during non-self related tasks [1]. We may hypothesize that rejecting offers from a proposer with whom people could easily empathise, implies a greater focus on first-person perspective, an

2011 - Functional connectivity of frontal components of the human mirror system: a PPI study. [Poster]
Lui, Fausta; Duzzi, Davide; Ghio, MARTA VIRGINIA; Bauleo, Armando; Porro, Carlo Adolfo

Introduction Great attention has been paid to the human mirror system (MNS) in recent years (Caspers et al., 2010; Rizzolatti & Sinigaglia 2010); among the peculiarities of the human MNS, the fact that it responds to action observation even in the absence of a target object (Lui et al., 2008). However, so far few studies have dealt with the functional connectivity of the components of this system (Skippers et al., 2007; Hattori et al., 2009; Xu et al., 2009; Emmorey et al., 2010). With the present work, we aimed at revealing patterns of connectivity of ventral premotor cortex/dorsal BA44 (PMv) and Broca area (BA44/45) during the observation of different types of gestures: Symbolic (SY) and Grasping (GR). 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 some common objects (glasses, cup, scissors, etc.) on a table. At intervals, an actor, of whom only the trunk and arms were visible, performed different kinds of hand movements: a) SY: non-object related symbolic actions (OK, hello, etc.); b) GR: grasping of an object. Three runs were carried out for each subject. Six movements for each class were shown in each run, alternated in pseudorandom order; each single movement was presented only once to each volunteer. 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. After a conventional GLM analysis, we assessed changes in functional connectivity related to the SY and GR observation tasks, by means of two separate PsychoPhysiologic Interaction (PPI) analyses (Friston et al., 1997). Foci in the right PMv and left BA44/45, identified by the conventional GLM analyses, were the seed regions. Group analyses were performed by random-effect models. Results Activity in right PMv during the observation of SY was positively related to activity in bilateral regions in posterior (occipito-temporo-parietal) cortex and cerebellum; during the observation of GR, the pattern was similar, but an additional correlated focus was present in the right inferior and middle frontal gyri, BA44/45/46 (Fig. 1). Activity in left BA44/45 during the observation of SY was positively related to activity in two foci: a larger focus in the left inferior and middle frontal gyri, mainly in BA45/46/47, and a second focus in the medial and superior frontal gyri, BA6/8, also mostly in the left hemisphere (Fig. 2). During the observation of GR, a very different pattern was present, with extensive bilateral clusters in sensorimotor and premotor cortex (mainly BA3/4/6/7 and BA6/8). Conclusions The present data suggest that right PMv and left Broca area are parts of different functional networks, differentially active during the observation of different meaningful arm-hand actions. The PMv connections to a mainly visual network during the observation of symbolic, intransitive movements are probably related to extracting visuo/spatial features of the observed scene; only during observation of grasping, PMv relates to the inferior frontal gyrus. On the other hand, the left Broca area has a specific pattern of connectivity with premotor regions involved in higher-order motor programming during the observation of symbolic gestures. References Caspers, S. et al. (2010), 'ALE meta-analysis of action observation and imitation in the human brain', NeuroImage, vol. 50, pp. 1148-1167. Emmorey, K. et al. (2010), ‘CNS activation and regional connectivity during pantomime observation: no engagement of the mirror neuron system for deaf signers’, Neuroimage vol. 49, pp. 994-1005. Hattori, N. et al. (2009), ‘Discrete parieto-frontal functional connectivity related to graspi

2010 - A quantitative comparison of BOLD fMRI responses to noxious and innocuous stimuli in the human spinal cord [Articolo su rivista]
Summers, Paul Eugene; Ferraro, Diana; Duzzi, Davide; Lui, Fausta; G. D., Iannetti; Porro, Carlo Adolfo

Recent studies have shown that functional magnetic resonance imaging (fMRI) can non-invasively assess spinal cord activity. Yet, a quantitative description of nociceptive and non-nociceptive responses in the human spinal cord, compared with random signal fluctuations in resting state data, is still lacking. Here we have investigated the intensity and spatial extent of blood oxygenation level dependent (BOLD) fMRI responses in the cervical spinal cord of healthy volunteers, elicited by stimulation of the hand dorsum (C6-C7 dermatomes). In a block design fMRI paradigm, periods (20 s each) of repetitive noxious (laser heat) or innocuous (brushing) stimulation were alternated with rest. To estimate the level of false positive responses, functional images were acquired during a separate run while subjects were at rest. In a first analysis of averaged peri-stimulus signals from all voxels within each half of the spinal cord, we found bilateral fMRI responses to both stimuli. These responses were significantly larger during noxious than during innocuous stimulation. No significant fMRI signal change was evident over corresponding time periods during the Rest run. In a second, general linear model analysis, we identified a voxel population preferentially responding to noxious stimulation, which extended rostro-caudally over the length (4 cm) of the explored spinal cord region. By contrast, we found no evidence of voxel populations responding uniquely to innocuous stimuli, or showing decreased activity following either kind of somatosensory stimulus. These results provide the first false-positive-controlled comparison of spinal BOLD fMRI responses to noxious and innocuous stimuli in humans, confirming and extending physiological information obtained in other species.

2010 - Neural bases of conditioned placebo analgesia [Articolo su rivista]
Lui, Fausta; Colloca, L.; Duzzi, Davide; Anchisi, Davide; Benedetti, F.; Porro, Carlo Adolfo

Despite growing interest in the placebo effect, the neural correlates of conditioned analgesia are still incompletely understood. We investigated herein on brain activity during the conditioning and post-conditioning phases of a placebo experimental paradigm, using event-related fMRI in 31 healthy volunteers.Brief laser heat stimuli delivered to one foot (either right or left) were preceded by different visual cues, signalling either painful stimuli alone, or painful stimuli accompanied by a (sham) analgesic procedure.Cues signalling the analgesic procedure were followed by stimuli of lower intensity in the conditioning session, whereas in the test session both cues were followed by painful stimuli of the same intensity. During the first conditioning trials, progressive signal increases over time were found during anticipation of analgesia compared to anticipation of pain, in a medial prefrontal focus centered on medial area BA8, and in bilateral lateral prefrontal foci. These frontal foci were adjacent to, and partially overlapped, those active during anticipation of analgesia in the test session, whose signal changes were related to the magnitudeof the placebo behavioral response, and those active during placebo analgesia. Specifically, a large focus in the right prefrontal cortex showed activity related to analgesia, irrespective of the expected side of stimulation. Analgesia was also related to decreased activity, detectable immediately following noxious stimulation, in parietal, insular and cingulate pain-related clusters. Our findings of dynamic changesin prefrontal areas during placebo conditioning, and of direct placebo effects on cortical nociceptive processing, add new insights into the neural bases of conditioned placebo analgesia.

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

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 - Pain Anticipation in the Cingulate Gyrus [Capitolo/Saggio]
Porro, Carlo Adolfo; Lui, Fausta

Throughout this chapter, we focus mainly on theinvolvement of the cingulate cortex in the anticipationof somatosensory input and specifi cally of pain. Thisissue has important theoretical and clinical implications,given the role of the cingulate cortex in themechanisms of pain and analgesia (see Chapters 14and 15). A specifi c question is that whether anticipationis able to affect the activity of pain-related populationsin the cingulate cortex and in the pain matrix in general.Indeed, it has long been hypothesized (James 1892)that essentially the same brain regions were implicatedboth in the anticipation and in the perception of astimulus; this hypothesis has now been directly testedby electrophysiological and functional imaging studiesin humans and non-human primates. Also, whenappropriate, we will briefl y compare the activity ofthe cingulate cortex during anticipation of painand during anticipation of other aversive or rewardevents. The specifi c goals of this chapter include thefollowing:1 Assess electrophysiological evidence of neurons activeduring pain anticipation in the cingulate cortex.2 Evaluate evidence from functional imaging studiesof activity changes related to somatosensory anticipationin different portions of the cingulate gyrus inhealthy volunteers and in pain patients.3 Appraise the modulation of basal- and stimulusevokedactivity of pain-related populations in thecingulate cortex and in other pain-related areas.4 Consider anticipation of pain and analgesia in termsof the potential underlying mechanisms and cingulatecircuits.

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

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 - 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

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 - Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli [Articolo su rivista]
Lui, Fausta; Duzzi, Davide; Corradini, Matteo; M., Serafini; Baraldi, Patrizia; Porro, Carlo Adolfo

Most imaging studies on the human pain system have concentrated so far on the spatial distribution of pain-related activity. In the present study, we investigated similarities and differences between the spatial and temporal patterns of brain activity related to touch vs. pain perception. To this end, we adopted an event-related functional magnetic resonance imaging (fMRI) paradigm allowing us to separately assess the activity related to stimulus anticipation, perception, and coding. The fMRI signal increases following brief mechanical noxious or non-noxious stimulation of the hand dorsum were largely overlapping in the contralateral and ipsilateral hemispheres, including portions of the parietal, insular, frontal and cingulate cortices. Higher activity following noxious stimulation was found in the contralateral mid-anterior insular cortex, in the anterior mid-cingulate cortex (aMCC) and in the adjacent dorso-medial frontal cortex. Significant decreases in fMRI signals following both tactile and painful stimuli were found in perigenual cingulate (pACC)/medial prefrontal cortex (MPF) and in the posterior cingulate/precuneus/paracentral lobule; more intense decreases were found in the pACC/MPF following painful stimuli. fMRI signal increases in the contralateral insula and in aMCC, but not in the parietal cortex, were more prolonged following painful than tactile stimuli. Moreover, a second peak of signal increases (albeit of lower intensity) was found in anterior insula and aMCC during pain intensity rating. These results show specific spatio-temporal patterns of cortical activity related to processing noxious vs. non-noxious mechanical stimuli.

2007 - Fisiologia: Un approccio integrato, 3° ediz. [Traduzione di Libro]
L., Agnati; Bigiani, Albertino; C., Franzini; Lui, Fausta

Negli anni trascorsi dalla precedente edizione, la fisiologia e la medicina hanno continuato la loro rapida evoluzione. Man mano che gli scienziati acquisiscono nuove conoscenze dei processi biologici fondamentali, le loro scoperte sono tradotte in nuovi trattamenti medici e in suggerimenti pe mantenerre lo stato di salute. In questa edizione abbiamo continuato ad aggiornare e a focalizzare i temi di base e i concetti di fisiologia per aiutare gli studenti a stabilire un modello mentale su come funziona il corpo umano.

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

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

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

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 - Functional activity mapping of brainstem nociceptive networks in animals [Capitolo/Saggio]
Porro, Carlo Adolfo; Lui, Fausta

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.

2005 - Fisiologia: Un approccio integrato, 2° ediz. [Traduzione di Libro]
L., Agnati; Bigiani, Albertino; C., Franzini; Lui, Fausta

Vi sono oggi opportunità straordinarie per un proficuo studio delle funzioni del corpo umano. Questo dipende dal fatto che non solo beneficiamo di secoli di studi compiuti da fisiologi che hanno costruito un corpus di conoscenze sulle funzioni dell'organismo umano, ma anche dal fatto che negli anni '70 vi sono stati progressi nel campo della biologia cellulare e molecolare così spettacolari che gli studenti talvolta guardano alla fisiologia come a una materia 'morta', in cui non resta più nulla da scoprire. In effetti, un tempo si pensava che decodificando l'intero genoma umano avremmo avuto la chiave del segreto della vita. Tuttavia, questa visione riduzionista della biologia ha i suoi limiti. Gli organismi viventi sono molto più di una semplice somma di parti, e scoprire le sequenze di geni e proteine in un laboratorio di biologia molecolare non sempre ci chiarisce il loro significato biologico in vivo. Ora, alle soglie del XXI secolo, i biologi molecolari chiedono aiuto ai fisiologi per la comprensione della funzione delle molecole nell'organismo in toto. L'integrazione della funzione a tutti i livelli, dalla molecola all'organismo vivente, è compito precipuo dei fisiologi.

2005 - The accessory optic system: basic organization with an update on connectivity, neurochemistry, and function [Capitolo/Saggio]
R. A., Giolli; R. H. I., Blanks; Lui, Fausta

The accessory optic system (AOS) is formed by a series of terminal nuclei receiving direct visual information from the retina via one or more accessory optic tracts. In addition to the retinal input, derived from ganglion cells that characteristically have large receptive fields, are direction-selective, and have a preference for slow moving stimuli, there are now well-characterized afferent connections with a key pretectal nucleus (nucleus of the optic tract) and the ventral lateral geniculate nucleus. The efferent connections of the AOS are robust, targeting brainstem and other structures in support of visual-oculomotor events such as optokinetic nystagmus and visual–vestibular interaction. This chapter reviews the newer experimental findings while including older data concerning the structural and functional organization of the AOS. We then consider the ontogeny and phylogeny of the AOS and include a discussion of similarities and differences in the anatomical organization of the AOS in nonmammalian and mammalian species. This is followed by sections dealing with retinal and cerebral cortical afferents to the AOS nuclei, interneuronal connections of AOS neurons, and the efferents of the AOS nuclei. We conclude with a section on Functional Considerations dealing with the issues of the response properties of AOS neurons, lesion and metabolic studies, and the AOS and spatial cognition.

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

2004 - Effects of ketamine anesthesia on central nociceptive processing in the rat: a 2-deoxyglucose study. [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Giuliani, Daniela; Vellani, Vittorio; Lui, Fausta; Baraldi, Patrizia

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

2004 - Fisiologia per la pratica infermieristica [Traduzione di Libro]
A., Calosso; Lui, Fausta

Questo testo, frutto dell'esperienza didattica degli autori con studenti di scienze infermieristiche appartenenti a corsi di studio di vari livelli, presenta una visione completa della fisiologia e dedica un'attenzione particolare a come i principi fisiologici discussi possono guidare la pratica infermieristica.I contenuti, corredati da numerose illustrazioni a colori, riflettono le concezioni più attuali sulla prestazione dell’assistenza sanitaria e si adattano perfettamente ai nuovi curricula del corso di laurea in infermieristica.La struttura a quattro colori del volume è particolarmente curata per permettere al lettore di individuare con facilità le diverse parti che compongono il testo: le osservazioni relative allo sviluppo, i suggerimenti per la pratica infermieristica e gli argomenti relativi alla pratica clinica che, integrati con i principi anatomici e fisiologici, consentono una migliore comprensione dell’argomento trattato.

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

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

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.

2004 - Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies [Articolo su rivista]
Porro, Carlo Adolfo; Lui, Fausta; P., Facchin; Maieron, Marta; Baraldi, Patrizia

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system. Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.

2004 - Single-Trial Characterization of BOLD fMRI Responses by Self-Organizing Neural Networks [Relazione in Atti di Convegno]
Manginelli, Angela; Duzzi, Davide; Lui, Fausta; Maieron, Marta; Baraldi, Patrizia

Functional magnetic resonance imaging (fMRI) plays a dominant role in human brain mapping studies. As of today, no standards exist for processing fMRI data and analysis techniques are often associated to the different stimulation paradigms used to acquire functional data. Being able to estimate the hemodynamic response following a single execution of a task permits to characterize its relationship to different aspects of the stimulus, and of the subject’s performance. This works is aimed to test a strategy for the characterization of single trial-related BOLD fMRI responses based on the self-organizing maps method of Kohonen (SOMs). Analysis have been carried out on synthetic fMRI images modeling activation and on data from a single-event fMRI experiment on one human subject performing a basic motor task. Results were able to define the potentiality range for this data-driven methodology in monitoring the evolution of the BOLD response deriving from a single stimulation.

2003 - Functional Imaging Correlates of Pain Perception [Articolo su rivista]
Porro, Carlo Adolfo; Baraldi, Patrizia; P., Facchin; Lui, Fausta; M., Maieron

Pain is a complex experience characterized by sensory,emotional, and cognitive aspects, which is likely to resultfrom the activity of large populations of central nervoussystem (CNS) cells. A crucial challenge in pain research istherefore to identify how the joint involvement of the differentnociceptive networks, that have been described byanatomical and electrophysiological techniques in experimentalanimals [1], gives rise to pain perception andmodulation.To this end, it is necessary to monitor functional activityof large neuronal arrays, in parallel with psychophysicalself-reports. This has been accomplished in humansusing different kinds of functional imaging techniques,among which positron emission tomography (PET) andfunctional magnetic resonance imaging (fMRI). Theyallow an indirect estimation of neural activity by investigatinglocal metabolic or hemodynamic changes, whichare closely related to the electrical activity of nerve cellsunder physiological circumstances [2]. In many studies, ablock experimental design was adopted: namely, brainactivity was compared among short periods of time (typically60 seconds in PET studies), each characterized bycontinuous (or repeated) innocuous or noxious stimulation.A single perceptual judgement was obtained at theend of each block, thus preventing appreciation of timerelatedchanges in nociceptive activity. Using blockdesigns makes it difficult to discriminate between brainactivity related to differences in the perceived pain intensity,to changes in the level of arousal during noxiousinput, or to anticipation of pain. The fMRI technique hasa better temporal resolution (usually on the order ofseconds) and it is therefore more suitable than PET totrace changes in functional activity of discrete brain areasover time. This can be done using brief stimuli (from hundredsmilliseconds to 2 seconds) in the so-called eventrelatedparadigms [3], using short epochs of 20-30 s, orduring time-varying pain induced by prolonged chemicalstimulation [4].Recent imaging studies have demonstrated the involvementof specific cortical and subcortical systems in differentaspects of the conscious experience of pain (seereview in [5]).

2003 - Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Lui, Fausta; Giuliani, Daniela; Pellegrini, Maddalena; Baraldi, Patrizia

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury. (C) 2003 International Association for the Study of Pain Published by Elsevier Science B.V. All fights reserved.

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

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.

2001 - Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey [Articolo su rivista]
Ra, Giolli; Km, Gregory; Da, Suzuki; Rhi, Blanks; Lui, Fausta; Kf, Betelak

Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a. and 7b to the basal pontine nuclei were studied using H-3-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei, (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.

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

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 - Saccadic eye movements are impaired in Duchenne muscular dystrophy [Articolo su rivista]
Lui, Fausta; Fonda, Sergio; L., Merlini; Corazza, Ruggero

Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity)were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by thelargest movements, whereas there were no significant ifferences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge, this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.

2000 - Fisiologia Umana: Un approccio integrato [Traduzione di Libro]
Di Paola, L.; Vantaggiato, G.; Lui, Fausta

Vi sono oggi opportunità straordinarie per un proficuo studio delle funzioni del corpo umano. Gli studenti talvolta guardano alla fisiologia come a una materia "morta", in cui non resta più nulla da scoprire. In effetti, un tempo si pensava che decodificcando l'intero genoma umano avremmo avuto la chiave del segreto della vita. Tuttavia, questa visione riduzionistica della biologia ha forti limiti. Gli organismi viventi sono molto di più di una semplice somma di parti. Ora, alle soglie del XXI secolo, i biologi molecolari chiedono aiuto ai fisiologi per la comprensione della funzione delle molecole nell'organismo in toto.

2000 - Ketamine effects on CNS nociceptive processing in the rat: 2-deoxyglucose studies [Relazione in Atti di Convegno]
Porro, Carlo Adolfo; Baraldi, Patrizia; Lui, Fausta; Murari, C; Cavazzuti, Milena

1999 - Neural circuits underlying ketamine induced oculomotor behavior in the rat: 2-deoxyglucose studies [Articolo su rivista]
Porro, Carlo Adolfo; Biral, Gp; Benassi, Carlo; Cavazzuti, Milena; Baraldi, Patrizia; Lui, Fausta; Corazza, Ruggero

Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by unidirectional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorsomedial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.

1999 - Olivofloccular circuit in oculomotor control: binocular optokinetic stimulation [Articolo su rivista]
Lui, Fausta; Benassi, Carlo; G., Biral; Corazza, Ruggero

The metabolic activation of the olivocerebellar pathway during binocular optokinetic stimulation was studied in the guinea pig, by means of the semiquantitative C-14-2-deoxyglucose (2DG) technique. The experimental group underwent binocular horizontal stimulation, whereas the control animals were either kept in the dark or allowed to view a stationary pattern. The local metabolic activity index in the dorsal cap of the inferior olive was higher on the side contralateral to the eye that had been stimulated in the temporonasal (T-N) direction in the horizontal group; in contrast, the floccular region showed higher activity on the side ipsilateral to the T-N-stimulated eye. These findings support the involvement of the olivocerebellar pathway in the horizontal optokinetic response. A phylogenetic hypothesis is suggested to explain inconsistent results found in the literature.

1998 - Neglect syndrome for aversive stimuli in a Macaque monkey with dorsomedial frontal cortex lesion [Articolo su rivista]
Lucchetti, Cristina; Lui, Fausta; Bon, Leopoldo

After a session of unit activity recording, one of our monkeys presented an epileptic attack, which provoked contralateral tilting movements. The following days, the animal performed saccades and fixation tasks correctly in all directions, while contralateral arm reaching movements were severely impaired. To establish if the neurological lesion had changed the orienting performance we considered two types of stimuli, pleasant and aversive. Pleasant stimuli, presented in the ipsilateral or contralateral hemifield, readily drew the attention of the animal. If the same stimuli were presented simultaneously in both hemifields, the monkey oriented itself only toward the ipsilateral one. Aversive stimuli evoked an aggressive reaction only when the stimulus was localized in the ipsilateral hemifield. The animal clearly neglected the aversive stimulus presented in the contralateral hemifield. The animal recovered completely in 30 days. The postmortem examination revealed a lesion in the dorsomedial frontal cortex. The combined attentional and motor deficits suggest that this area may be involved in the preparation and execution of movements triggered by the affective meaning of the stimulus. (C) 1998 Elsevier Science Ltd. All rights reserved.

1997 - Visual corticopontine projections in the guinea pig: an autoradiographic study [Articolo su rivista]
Lui, Fausta; J., Aldon

The goal of this study is to characterize the anatomical organization of the visual cortical output to the basal pontine nuclei in the guinea pig. Data from the Literature show that guinea pigs exhibit different optokinetic oculomotor behaviors with respect to rats and rabbits. Namely, they present a fast rise in eye movement velocity at stimulus onset and a better performance in monocular horizontal stimulation. Possible differences in the visual corticopontocerebellar pathway might explain these peculiarities. The pontine projections from the primary visual cortex were studied with the method of the anterograde axonal transport of [H-3]leucine. The terminal labeling forms prominent patches, ipsilaterally to the cortical injection, throughout the rostrocaudal extent of the pontine nuclei, predominantly in the dorsolateral region. At the intermediate rostrocaudal level, some foci of labeling are found ventrolaterally as well. Sparse fields are present also in the medial pontine nuclei and in the nucleus reticularis tegmenti pontis, but only when the injection site extends to secondary visual areas, either lateral or medial. The present description of the corticopontine projections in guinea pigs is in substantial agreement with the projections previously described in rats, with a few differences, namely: (1) the recipient area extends more caudally; (2) secondary visual areas project to the nucleus reticularis tegmenti pontis.

1996 - Aspetti anatomici del riflesso otticocinetico [Capitolo/Saggio]
Lui, Fausta

Aspetti anatomici del riflesso otticocinetico- Cenni storici e definizioni- Connessioni- Cenni di ultrastruttura e neurochimica

1995 - Projections from visual areas of the cerebral cortex to pretectal nuclear complex, terminal accessory optic nuclei, and superior colliculus in macaque monkey [Articolo su rivista]
Lui, Fausta; Km, Gregory; Rhi, Blanks; Ra, Giolli

The purpose of this study was to analyze the projections from visually related areas of the cerebral cortex of rhesus monkey to subcortical nuclei involved in eye-movement control; i.e., the pretectal nuclear complex, the terminal nuclei of the accessory optic system (AOS), and the superior colliculus (SC). The anterograde tracer H-3-leucine was pressure injected bilaterally into the cortex of six monkeys (for a total of 12 cases) involving the primary visual cortex (area 17); the medial prestriate cortex (medial 18/19); dorsomedial area 19; the caudal portion of the cortex of the superior temporal sulcus, upper bank (cytoarchitectural area OAa) and lower bank (area PGa); the lower bank of the caudal lateral intraparietal sulcus (area POa); and the inferior parietal lobule (area 7). The results revealed that the pretectal nucleus of the optic tract received inputs from medial prestriate cortex, dorsomedial part of area 19, OAa, and PGa. The posterior pretectal nucleus received sparse projections from area 7 and the cortex lining the intraparietal sulcus (dorsomedial part of area 19 and POa). The pretectal olivary nucleus was targeted by neurons in cortex of dorsomedial area 19, and the anterior pretectal nucleus was targeted by neurons in both dorsomedial 19 and area 7. The nuclei of the AOS (dorsal terminal; lateral terminal; and interstitial nuclei of the superior fasciculus, posterior and medial fibers) received projections exclusively from areas OAa and PGa. Furthermore, in one case with PGa injection, the medial terminal nucleus, dorsal portion, was also labeled. The visual cortical areas studied projected differentially upon the SC laminae. The primary visual area 17 projected only to the superficial laminae, i.e., stratum zonale (SZ), stratum griseum superficiale (SGS), and stratum opticum (SO). On the other hand, the medial portion of the prestriate cortex and caudal OAa and PGa targeted the superficial and intermediate laminae, i.e., SZ, SGS, SO, and stratum griseum intermediale (SGI), whereas caudal area POa projected primarily to the intermediate layer SGI. Rostral area 7 (mainly 7b) neurons terminated in the stratum album intermediale (SAI); no SC terminals were found in a case in which caudal area 7 (mainly 7a) was injected.

1995 - Projections of the lateral terminal accessory optic nucleus of the common marmoset (Callitrix Jacchus) [Articolo su rivista]
BLANKS R., H; CLARKE R., J; Lui, Fausta; GIOLLI R., A; PHAM S., V; Torigoe, Y.

The connections of the lateral terminal nucleus (LTN) of the accessory optic system (AOS) of the marmoset monkey were studied with anterograde 3H-amino acid light autoradiography and horseradish peroxidase retrograde labeling techniques. Results show a first and largest LTN projection to the pretectal and AOS nuclei including the ipsilateral nucleus of the optic tract, dorsal terminal nucleus, and interstitial nucleus of the superior fasciculus (posterior fibers); smaller contralateral projections are to the olivary pretectal nucleus, dorsal terminal nucleus, and LTN. A second, major bundle produces moderate-to-heavy labeling in all ipsilateral, accessory oculomotor nuclei (nucleus of posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch) and nucleus of Bechterew; some of the fibers are distributed above the caudal oculomotor complex within the supraoculomotor periaqueductal gray. A third projection is ipsilateral to the pontine and mesencephalic reticular formations, nucleus reticularis tegmenti pontis and basilar pontine complex (dorsolateral nucleus only), dorsal parts of the medial terminal accessory optic nucleus, ventral tegmental area of Tsai, and rostral interstitial nucleus of the medial longitudinal fasciculus. Lastly, there are two long descending bundles: (1) one travels within the medial longitudinal fasciculus to terminate in the dorsal cap (ipsilateral >> contralateral) and medial accessory olive (ipsilateral only) of the inferior olivary complex. (2) The second soon splits, sending axons within the ipsilateral and contralateral brachium conjunctivum and is distributed to the superior and medial vestibular nuclei. The present findings are in general agreement with the documented connections of LTN with brainstem oculomotor centers in other species. In addition, there are unique connections in marmoset monkey that may have developed to serve the more complex oculomotor behavior of nonhuman primates.

Lui, Fausta; Giolli, Ra; Blanks, Rh; Tom, Em

The primary goal of this study was to determine whether the striate cortex (Oc 1) of the guinea pig projects to the pretectal nucleus of the optic tract (NOT), the first postretinal station of the horizontal optokinetic pathway, and, if so, to analyze the anatomical organization of this cortico-NOT projection. Other goals of this investigation are to identify other pretectal nuclear projections from the visual cortex in the guinea pig, and to determine whether there is any visuotopic organization in this pathway. Axonal tracers (biocytin or H-3-leucine) were injected into the striate cortex (Oc 1), and the tissue processed with histochemical or light autoradiographic techniques. All subcortical terminal labeling is ipsilateral in the basal ganglia and thalamic nuclei. Furthermore, projections are traced to the ipsilateral brainstem, including two areas of the pretectal complex: (1) one in the NOT, extending in some cases to the adjacent lateral portion of the posterior pretectal nucleus (PPN), and (2) one in the pars compacta of the anterior pretectal nucleus (APNc). The terminal fields in the APN are consistently located rostrally in the dorsolateral portion of the nucleus, independently of the injection site in Oc 1, whereas in the NOT the terminal fields shift slightly after injections placed in different locations in the striate cortex. A correlation of the injection sites in Oc 1 and terminal fields in the NOT reveals a loose topographic organization in the cortico-NOT projection; accordingly, the rostrocaudal axis of the striate cortex projects to the lateromedial axis of the NOT, with a 90 degrees rotation, whereas lateral parts of the striate cortex project diffusely throughout the rostrocaudal extent of the NOT. These data show for the first time that the NOT in the guinea pig receives a substantial projection from the visual cortex. Given the fact that in the guinea pig the optokinetic nystagmus shares some of the characteristics found in cat and monkey (i.e., consistent initial fast rise in the slow phase velocity and reduced asymmetry in monocular stimulation), the present findings lend support to the hypothesis that a cortical input to the NOT is a necessary condition for these oculomotor properties to be present.

1994 - Spatio-temporal pattern of eye movements induced by ketamine in the rat [Capitolo/Saggio]
Gp, Biral; Benassi, Carlo; Lui, Fausta; R., Corazza

Eye movements up to seven hours after ketamine injection were recorded in Long-Evans rats by means of a phase detection search coil apparatus. A flutter-like oculomotor pattern immeditely appeared after drug administration, lasting about one hour; it was characterized by unidirectional slow eye movements with superimposed bursts of saccades. While saccadic dynamics was always within the normal range, the eyes were unable to maintain a steady post-saccadic position. Every saccade was followed by a quick drift back towards the initial position. As the rat aroused, paroxysmal ocular motility stopped and spontaneous well isolated, now bidirectional saccades appeared. The post-saccadic drift persisted. Ocular flutter-like behavior could result from a sustained activation of the saccade generator, whereas impairment of gaze holding might be due to the neural integrator suppression.

Lui, Fausta; Benassi, Carlo; Biral, Gp; Ferrari, Renata

Kainic acid (KA) damages retinal cells, thus impairing axonal anterograde transport of labeled aminoacids when injected intravitreally. In this study, Long-Evans rats were injected with KA into one eye, and seven days later were binocularly injected with C-14-valine. The extent of residual retinal afferents to two pretectal nuclei was calculated as the percentage of the contralateral, intact side. Projections to the nucleus of the optic tract (first relay station of the optokinetic pathway) appear significantly more affected than those to the olivary pretectal nucleus (involved in the pupillary light response). These results suggest a correlation between the functional properties of retinal ganglion cells and distinctive biochemical characteristics, such as their susceptibility to KA.

1991 - Correlation between amount of retinal afferents to the pretectal nucleus of the optic tract and dorsal terminal accessory optic nucleus and performance of horizontal optokinetic reflex in rat [Articolo su rivista]
Benassi, Carlo; Lui, Fausta; Biral, Giampaolo; Ferrari, Renata; Corazza, Ruggero

Intraocular kainic acid injection in Long-Evans rats induces loss of retinal afferents to subcortical visual centers as assessed by the axoplasmic transport of [C-14]valine. The optical terminal fields of the pretectal nucleus of the optic tract (NOT), superior colliculus and accessory optic system (AOS) nuclei appear particularly affected. Since NOT and the AOS dorsal terminal nucleus (DTN) represent the first relay station of the visuomotor pathway mediating horizontal optokinetic nystagmus (HOKR), we have studied the characteristics of HOKR after various degrees of retinal deafferentiation of these nuclei induced by intraocular KA injection. Taking advantage of the arrangement of the primary optic projections to NOT-DTN, that in rats are almost entirely crossed, in each animal, monocular HOKR induced by stimulation of the injected eye was compared to monocular HOKR elicited by stimulation of the intact, ipsilateral eye. Following NOT-DTN optic denervation, HOKR gain always worsened, and in a way, that the greater the deficits of retinal afferents, the greater the HOKR inability to compensate for visual motion. Furthermore, for any given retinal denervation the higher the stimulus velocity, the greater the HOKR deficit. While the correlation between HOKR gain and the amount of retinal afferents to NOT-DTN would seem to indicate a functional homogeneity of the retinal ganglion cells sending axons to these nuclei, the finding that the extent of HOKR impairment also varied with velocity might not support the above view.

Ferrari, Renata; G. P., Biral; Benassi, Carlo; Lui, Fausta

Long Evans rats monocularly injected with the kainic acid (KA), were exposed to "tonic" (diffuse steady light, stationary pattern, total darkness) and "phasic" (flashing, moving pattern) stimulations. By means of the autoradiographic 2-deoxyglucose (2DG) technique we assessed the functional activity of the Superior Colliculus (SC) contralateral to the injected eye as compared to the normal eye SC. In the control SC all "tonic" stimulations determined low 2DG uptake not modified by the intraocular KA injection. On the contrary, "phasic" stimulations elicited a strong 2DG consumption in the normal SC, with a peculiar pattern of distribution depending on the kind of stimulus. Considering the total 2DG uptake as the added intrinsic and afferent metabolism, KA was able to affect only the latter, decreasing two-fold that expected for the afferent input loss. These findings can suggest a possible KA effect on off-line ganglion cells and, on the other side, they confirm the role of the SC in discriminating "phasic" and sudden phenomena from "tonic" and continuous ones.

Lui, Fausta; Biral, Gp; Benassi, Carlo; Ferrari, Renata; Corazza, R.

The intrinsic morpho-functional organization of the medial terminal nucleus of the accessory optic system was investigated in the guinea pig. The distribution of the retinal afferents, as assessed by the axoplasmic transport of 14C-valine, showed a remarkable asymmetry within the nucleus. Thus, while the retinal terminal field covered the entire medial terminal nucleus, by far the largest density of labeled retinofugal axon terminals was found within its dorsal division. In this same portion of the nucleus, we found the greatest density of large cells and the maximum intensity of functional activation, this latter as estimated by the increase in metabolic activity of neurons using the 14C-2-deoxyglucose autoradiographic method in the vertical and horizontal whole-field movement in the visual field.

1989 - The interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) in the guinea pig: another nucleus of the accessory optic system processing the vertical retinal slip signal. [Articolo su rivista]
Benassi, Carlo; Biral, Giampaolo; Lui, Fausta; Porro, Carlo Adolfo; Corazza, Ruggero

As in rabbit, gerbil, and rat, the guinea pig interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) is a sparse assemblage of neurons scattered among the fibers forming the fasciculus bearing this name. Most of the INSFp neurons are small and are ovoid in shape. Interspersed among these, are a few larger, elongated neurons whose density becomes greater and whose shape becomes fusiform in correspondence to the zone of transition from the superior fasciculus to the ventral part of the medial terminal nucleus (MTN). Like the MTN, the INSFp is activated by retinal-slip signals evoked by whole-field visual patterns moving in the vertical direction, as shown by the increase of 14C-2-deoxyglucose (2DG) uptake into this nucleus. At the same level of luminous flux, neither pattern moving in the horizontal direction nor the same pattern held stationary can elicit increases in the INSFp 2DG assumption. The specificity of the observed increases in metabolic rates in INSFp following vertical whole-field motion suggests that this assemblage of neurons relays visual signals used in the control of vertical optokinetic nystagmus.

1987 - Correspondence between the activation of the nucleus tractus optici and the appearance of optokinetic nystagmus in the albino guinea pig [Articolo su rivista]
Biral, Giampaolo; Benassi, Carlo; Lui, Fausta; Porro, Carlo Adolfo; Cavazzuti, Milena; Corazza, Ruggero

It is known that albinism is accompanied by several visual disturbances. The anomalous features of the optokinatic eye nystagmus (OKN) found in albino strains of different species have been ascribed to he same visual defects. The occurrence of a clear horizontal OKN in albino Guinea pig led us to investigate activity in the Nucleus of the optic tract (NOT)