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

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

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

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

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

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

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

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

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

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

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

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

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

Pugnaghi, Matteo; Benuzzi, Francesca; Monti, Giulia; Farinelli, Valentina; Nichelli, Paolo Frigio; Meletti, Stefano

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

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