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Davide DUZZI

Personale tecnico amministrativo
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Sc. Biomediche

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Pubblicazioni

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

2017 - Voluntary modulation of mental effort investment: An fMRI study [Articolo su rivista]
Khachouf, Omar T.; Chen, Gang; Duzzi, Davide; Porro, Carlo A.; Pagnoni, Giuseppe
abstract

Mental effort is a common phenomenological construct deeply linked to volition and self-control. While it is often assumed that the amount of exertion invested in a task can be voluntarily regulated, the neural bases of such faculty and its behavioural effects are yet insufficiently understood. In this study, we investigated how the instructions to execute a demanding cognitive task either "with maximum exertion" or "as relaxed as possible" affected performance and brain activity. The maximum exertion condition, compared to relaxed execution, was associated with speeded motor responses without an accuracy trade-off, and an amplification of both task-related activations in dorsal frontoparietal and cerebellar regions, and task-related deactivations in default mode network (DMN) areas. Furthermore, the visual cue to engage maximum effort triggered an anticipatory widespread increase of activity in attentional, sensory and executive regions, with its peak in the brain stem reticular activating system. Across individuals, this surge of activity in the brain stem, but also in medial wall cortical regions projecting to the adrenal medulla, positively correlated with increases in heart rate, suggesting that the intention to willfully modulate invested effort involves mechanisms related to catecholaminergic transmission and a suppression of DMN activity in favor of externally-directed attentional processes.

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

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

2014 - 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
abstract

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 http://www.abstractsonline.com/submit/SubmitPrin... 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
abstract

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.

2013 - Human Parietofrontal Networks Related to Action Observation Detected at Rest [Articolo su rivista]
E., Molinari; Baraldi, Patrizia; M., Campanella; Duzzi, Davide; L., Nocetti; Pagnoni, Giuseppe; Porro, Carlo Adolfo
abstract

Recent data show a broad correspondence between human resting state and task-related brain networks. We performed a functional magnetic resonance imaging (fMRI) study to compare, in the same subjects, the spatial independent component analysis (ICA) maps obtained at rest and during the observation of either reaching/grasping hand actions or matching static pictures. Two parietofrontal networks were identified by ICA from action observation task data. One network, specific to reaching/grasping observation, included portions of the anterior intraparietal cortex and of the dorsal and ventral lateral premotor cortices. A second network included more posterior portions of the parietal lobe, the dorsomedial frontal cortex, and more anterior and ventral parts,respectively, of the dorsal and ventral premotor cortices, extending toward Broca’s area; this network was more generally related to the observation of hand action and static pictures. A good spatial correspondence was found between the 2 observation-related ICA maps and 2 ICA maps identified from resting-state data. The anatomical connectivity among the identified clusters was tested in the same volunteers, using persistent angular structure--MRI and deterministic tractography. These findings extend available knowledge of human parietofrontal circuits and further support the hypothesis of a persistent coherence within functionally relevant networks during rest.

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
abstract

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.

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
abstract

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
abstract

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 - “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
abstract

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 (http://afni.nimh.nih.gov/afni/doc/manual/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
abstract

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
abstract

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
abstract

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
abstract

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

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

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

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

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

2008 - 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
abstract

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

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

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

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

2005 - Analisi di dati fMRI-BOLD a singolo evento: un approccio con reti neurali non supervisionate [Articolo su rivista]
Duzzi, Davide; Manginelli, Angela; Maieron, Marta; Porro, Carlo Adolfo; Baraldi, Patrizia
abstract

Negli studi di risonanza magnetica funzionale (fMRI) cerebrale hanno assunto particolare rilevanza i protocolli di stimolazione basati su singoli eventi. Nel lavoro viene descritta una strategia di analisi di dati fMRI-BOLD, con lo scopo di rilevare il profilo temporale della risposta ad ogni singola stimolazione, nelle diverse aree cerebrali coinvolte. Il metodo si avvale di una fase di pre-elaborazione dei dati finalizzata ad incrementare il basso contrasto segnale-rumore tipico di dati derivanti da un singolo evento e di una fase di classificazione, caratterizzazione e localizzazione delle risposte realizzata implementando una rete neurale basata sull’algoritmo di Kohonen delle mappe auto-organizzanti (SOMs). I risultati, ottenuti sia su immagini fMRI simulate, che su dati reali relativi ad un soggetto umano, mostrano la validita’ di questo approccio guidato dai dati nell’identificazione delle risposte ad una singola stimolazione e ne forniscono i limiti di applicabilita’.

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
abstract

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.