Littérature scientifique sur le sujet « Inter-hemispheric connectivity »

IntroductionThe functional interplay between brain hemispheres is fundamental for behavioral, cognitive and emotional control. Several pathophysiological aspects of eating disorders (EDs) have been investigated by the use of functional Magnetic Resonance Imaging (fMRI).ObjectivesThe objective of the study was to investigate functional brain asymmetry of resting-state fMRI correlations in symptomatic patients with anorexia nervosa (AN) and bulimia nervosa (BN).AimsWe aimed at revealing whether brain regions implicated in reward, cognitive control, starvation and emotion regulation show altered inter-hemispheric functional connectivity in patients with AN and BN.MethodsUsing resting-state fMRI, voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) analyses in two canonical slow frequency bands (“Slow-5”, “Slow-4”) were studied in 15AN and 13BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA).ResultsCompared to HC, AN patients exhibited reduced VMHC in cerebellum, insula and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the ‘Slow-5′Band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs callosal FA correlations were found.ConclusionsThese anomalies indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Background. Abnormalities in white matter integrity and specific functional network alterations have been increasingly reported in patients with Parkinson’s disease (PD). However, little is known about the inter-hemispheric interaction in PD.Methods. Fifty-one drug naive patients with PD and 51 age- and gender-matched healthy subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared the inter-hemispheric resting-state functional connectivity between patients with PD and healthy controls, using the voxel-mirrored homotopic connectivity (VMHC) approach. Then, we correlated the results from VMHC and clinical features in PD patients.Results. Relative to healthy subject, patients exhibited significantly lower VMHC in putamen and cortical regions associated with sensory processing and motor control (involving sensorimotor and supramarginal cortex), which have been verified to play a critical role in PD. In addition, there were inverse relationships between the UPDRS motor scores and VMHC in the sensorimotor, and between the illness duration and VMHC in the supramarginal gyrus in PD patients.Conclusions. Our results suggest that the functional coordination between homotopic brain regions is impaired in PD patients, extending previous notions about the disconnection of corticostriatal circuit by providing new evidence supporting a disturbance in inter-hemispheric connections in PD.

The application of voxel-mirrored homotopic connectivity (VMHC) analysis to study the central mechanism of migraine has been limited. Furthermore, little is known about inter-hemispheric functional connectivity (FC) alterations during resting state in female patients with migraine. This study aimed to investigate potential interictal VMHC impairments in migraine without aura (MwoA) patients and the relationship between connectivity alterations and clinical parameters. Resting-state functional magnetic resonance imaging data and clinical information were acquired from 43 female MwoA patients and 43 matched healthy controls. VMHC analysis was used to compare differences between these two groups, and brain regions showing significant differences were chosen as a mask to perform a seed-based FC group comparison. Subsequent correlation analysis was conducted to explore the relationship between abnormal inter-hemispheric FC and clinical data. Compared with healthy controls, female MwoA patients revealed significantly decreased VMHC in the bilateral cerebellum; cuneus; and lingual, middle occipital, precentral and postcentral gyri. Seed-based FC analysis indicated disrupted intrinsic connectivity in the cerebellum, and default mode, visual and sensorimotor network. These VMHC and FC abnormalities were negatively correlated with clinical indexes including duration of disease, migraine days and visual analogue scale. These inter-hemispheric FC impairments and correlations between abnormal VMHC and FC and clinical scores may improve our understanding of the central mechanism of female-specific migraine.

Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and standardized language assessment. We hypothesized that functional networks obtained from tb-fMRI would show connectivity changes over time, with increased right-hemispheric participation. We recruited five right-handed patients (4M, mean age 47.6Y) with left-hemispheric LGG. Tb-fMRI and language assessment were conducted pre-operatively (pre-op), and post-operatively: post-op1 (4–8 months), post-op2 (10–14 months) and post-op3 (16–23 months). We computed the individual functional networks applying optimal percolation thresholding. Language dominance and hemispheric connectivity were quantified by laterality indices (LI) on fMRI maps and connectivity matrices. A fixed linear mixed model was used to assess the intra-patient correlation trend of LI values over time and their correlation with language performance. Individual networks showed increased inter-hemispheric and right-sided connectivity involving language areas homologues. Two patterns of language reorganization emerged: Three/five patients demonstrated a left-to-codominant shift from pre-op to post-op3 (type 1). Two/five patients started as atypical dominant at pre-op, and remained unchanged at post-op3 (type 2). LI obtained from tb-fMRI showed a significant left-to-right trend in all patients across timepoints. There were no significant changes in language performance over time. Type 1 language reorganization may be related to the treatment, while type 2 may be tumor-induced, since it was already present at pre-op. Increased inter-hemispheric and right-side connectivity may represent the initial step to develop functional plasticity.

Mon travail de thèse s'inscrit dans une approche d'intégration multimodale et multi-échelle qui a conduit à l'émergence de la neuroimagerie cognitive et de population. Il repose sur deux modalités de cartes fonctionnelles tridimensionnelles cérébrales obtenues en IRMf : les cartes d'activation permettant de visualiser les régions dont l’activité est évoquée par un processus cognitif et les cartes de connectivité intrinsèque mesurant la synchronisation entre des régions spatialement distantes, mais connectées fonctionnellement. J'ai appliqué à ces deux types de cartes de nouvelles méthodologies statistiques permettant de traiter à la fois les dimensions individuelles et spatiales. Dans une première partie, j'ai conçu des atlas de régions cérébrales dédiées à des fonctions cognitives spécifiques, basés sur leur latéralisation hémisphérique et ciblant une population sélectionnée pour sa faible variabilité. Je présente ici les deux premiers atlas du langage. En effet, bien qu'il existe de nombreuses approches pour cartographier les régions du langage chez les patients, il n'existait pas d'atlas des réseaux langagiers chez les individus sains. J’ai tout d’abord identifié les régions activées dans l'hémisphère gauche et asymétriques gauche, à la fois pendant la production, l'écoute et la lecture de phrases, chez 137 individus sains droitiers. L’analyse de la connectivité intrinsèque entre les 32 régions identifiées a permis de mettre en évidence qu'elles faisaient partie de 3 réseaux fonctionnels distincts. Le tout constituant ainsi l’atlas cérébral SENSAAS (SENtence Supramodal Areas AtlaS). Parmi ces réseaux, l'un comprenant 18 régions contient les zones essentielles du langage (SENT_CORE), c'est-à-dire les aires cérébrales dont la lésion entraînerait une déficience dans l'intégration du sens de la parole. Plus particulièrement, SENT_CORE contient 3 régions clés (hubs) de l’intégration et de la diffusion de l'information situées au niveau de l’aire de Broca et de Wernicke. J'ai ensuite appliqué cette méthodologie à l’élaboration d’un atlas des réseaux du traitement du mot. J’ai ainsi identifié 21 régions cérébrales organisées en 2 réseaux distincts, dont un réseau phonologique incluant la boucle audio-motrice. Pour la première fois, une forte connectivité intrinsèque entre la boucle audio-motrice de l’hémisphère gauche et le traitement prosodique situé au niveau du sillon temporal supérieur de l’hémisphère droit a été mis en évidence. Enfin, j'ai développé une nouvelle méthode d’étude de la variabilité de données tridimensionnelles. Cette nouvelle méthode comporte deux outils mathématiques différents se basant sur un algorithme de classification ascendante hiérarchique. Le premier permet d'identifier les variables conduisant à une instabilité des partitions, le second permet d'extraire des sous-populations stables d'une population de départ. Les applications de l’ensemble de ce travail sont nombreuses : j'ai par exemple utilisé le réseau SENT_CORE pour étudier la variabilité interindividuelle de la latéralisation hémisphérique des aires supramodales de la phrase. J’ai ainsi identifié deux groupes de sujets typiques asymétriques gauche pour le langage, avec une forte connectivité intra-hémisphérique gauche et une faible connectivité inter-hémisphérique, ainsi qu’un groupe de sujets atypiques : asymétriques droit pour le langage, présentant une forte connectivité intrinsèque des réseaux du langage dans les deux hémisphères et une forte connectivité inter-hémisphérique. SENSAAS a également été utilisé afin d’étudier le support génétique de l’atypicalité du langage, ainsi que pour la caractérisation topologique des réseaux mnésiques et linguistiques des individus souffrant d'épilepsie temporale. La nouvelle méthode d’évaluation de la variabilité interindividuelle a, elle, été utilisée afin d’évaluer la stabilité des réseaux intrinsèques d’un nouvel atlas fonctionnel adapté aux individus de plus de 55 ans
My thesis work is part of a multi-modal and multi-scale integration approach which has led to the emergence of cognitive and population neuroimaging. More specifically, fMRI provides two types of three-dimensional functional brain maps: activation maps allowing for visualizing brain regions directly involved in a cognitive process, and intrinsic connectivity maps measuring the synchronization between spatially distant but functionally connected regions. I have applied new statistical methodologies to these two types of maps, allowing me to deal with both the individual and the spatial dimensions. In the first part, I designed atlases of brain regions dedicated to specific cognitive functions, based on their hemispheric lateralization and targeting a population selected for its low variability. I present here the first two language atlases. Indeed, although there are many approaches to map language areas in patients, there was no atlas of networks supporting language functions in healthy individuals so far. I first identified left activated and left asymmetrical regions, both during sentence production, listening and reading, in 137 healthy right-handed individuals. Analysis of the intrinsic connectivity between the 32 identified regions reveals that they are part of 3 distinct functional networks, which constitute the SENSAAS (SENtence Supramodal Areas AtlaS) brain atlas. Among these networks, one with 18 regions contains the essential language areas (SENT_CORE), i.e. the brain areas whose lesion leads to an impairment in the integration of the meaning of speech. Specifically, SENT_CORE contains 3 hubs supporting the information integration and dissemination, localized in the Broca and Wernicke area. I then applied this methodology to the elaboration of an atlas of word processing networks. I identified 21 brain regions organized into 2 distinct networks, one of which is a phonological network including the audio-motor loop. For the first time, a strong intrinsic connectivity between the left audio-motor loop and the prosodic processing, located in the upper temporal sulcus of the right hemisphere, is evidenced. Finally, I developed a new method for studying the variability of three-dimensional data. This new method includes two different mathematical tools based on hierarchical agglomerative clustering algorithms. The first one makes it possible to identify variables leading to partition instability, the second one allows for extracting stable sub-populations from a starting population. The applications of all of this work are numerous: for example, I used the SENT_CORE network to study the inter-individual variability of hemispheric lateralization of the sentence supramodal areas. I have thus identified two groups of typical asymmetric left language individuals, with high left intra-hemispheric intrinsic connectivity and low inter-hemispheric connectivity, and a group of atypical individuals: rightward asymmetrical for language, with high intrinsic connectivity of language networks in both hemispheres and high inter-hemispheric connectivity. SENSAAS has also been used to study the genetic support of language atypicality, as well as for the topological characterization of the memory and language networks of individuals with mesial temporal lobe epilepsy. The new method for assessing inter-individual variability was used to evaluate the stability of the intrinsic networks of a new functional atlas adapted for late adulthood

La douleur est une expérience perceptive comportant de nombreuses dimensions. Ces dimensions de douleur sont inter-reliées et recrutent des réseaux neuronaux qui traitent les informations correspondantes. L’élucidation de l'architecture fonctionnelle qui supporte les différents aspects perceptifs de l'expérience est donc une étape fondamentale pour notre compréhension du rôle fonctionnel des différentes régions de la matrice cérébrale de la douleur dans les circuits corticaux qui sous tendent l'expérience subjective de la douleur. Parmi les diverses régions du cerveau impliquées dans le traitement de l'information nociceptive, le cortex somatosensoriel primaire et secondaire (S1 et S2) sont les principales régions généralement associées au traitement de l'aspect sensori-discriminatif de la douleur. Toutefois, l'organisation fonctionnelle dans ces régions somato-sensorielles n’est pas complètement claire et relativement peu d'études ont examiné directement l'intégration de l'information entre les régions somatiques sensorielles. Ainsi, plusieurs questions demeurent concernant la relation hiérarchique entre S1 et S2, ainsi que le rôle fonctionnel des connexions inter-hémisphériques des régions somatiques sensorielles homologues. De même, le traitement en série ou en parallèle au sein du système somatosensoriel constitue un autre élément de questionnement qui nécessite un examen plus approfondi. Le but de la présente étude était de tester un certain nombre d'hypothèses sur la causalité dans les interactions fonctionnelle entre S1 et S2, alors que les sujets recevaient des chocs électriques douloureux. Nous avons mis en place une méthode de modélisation de la connectivité, qui utilise une description de causalité de la dynamique du système, afin d'étudier les interactions entre les sites d'activation définie par un ensemble de données provenant d'une étude d'imagerie fonctionnelle. Notre paradigme est constitué de 3 session expérimentales en utilisant des chocs électriques à trois différents niveaux d’intensité, soit modérément douloureux (niveau 3), soit légèrement douloureux (niveau 2), soit complètement non douloureux (niveau 1). Par conséquent, notre paradigme nous a permis d'étudier comment l'intensité du stimulus est codé dans notre réseau d'intérêt, et comment la connectivité des différentes régions est modulée dans les conditions de stimulation différentes. Nos résultats sont en faveur du mode sériel de traitement de l’information somatosensorielle nociceptive avec un apport prédominant de la voie thalamocorticale vers S1 controlatérale au site de stimulation. Nos résultats impliquent que l'information se propage de S1 controlatéral à travers notre réseau d'intérêt composé des cortex S1 bilatéraux et S2. Notre analyse indique que la connexion S1→S2 est renforcée par la douleur, ce qui suggère que S2 est plus élevé dans la hiérarchie du traitement de la douleur que S1, conformément aux conclusions précédentes neurophysiologiques et de magnétoencéphalographie. Enfin, notre analyse fournit des preuves de l'entrée de l'information somatosensorielle dans l'hémisphère controlatéral au côté de stimulation, avec des connexions inter-hémisphériques responsable du transfert de l'information à l'hémisphère ipsilatéral.
Pain is a perceptual experience comprising many dimensions. These pain dimensions interrelate with each other and recruit neuronal networks that process the corresponding information. Elucidating the functional architecture that supports different perceptual aspects of the experience is thus, a fundamental step to our understanding of the functional role of different regions in the cerebral pain matrix that are involved in the cortical circuitry underlying the subjective experience of pain. Among various brain regions involved in the processing of nociceptive information, primary and secondary somatosensory cortices (S1 and S2) are the main areas generally associated with the processing of sensory-discriminative aspect of pain. However the functional organization in these somatosensory areas is not completely clear and relatively few studies have directly examined the integration of information among somatic sensory regions. Thus, several questions remain regarding the hierarchical relationship between S1 and S2, as well as the functional role of the inter-hemispheric connections of the homologous somatic sensory areas. Likewise, the question of serial or parallel processing within the somatosensory system is another questionable issue that requires further investigation. The purpose of the present study was to test a number of causal hypotheses regarding the functional interactions between S1 and S2, while subjects were receiving painful electric shocks. We implemented a connectivity modeling approach, which utilizes a causal description of system dynamics, in order to study the interactions among activation sites defined by a data set derived from a functional imaging study. Our paradigm consists of 3 experimental scans using electric shock stimuli, with the stimulus intensity changing from moderately painful (level 3), to slightly painful (level 2), and to completely non-painful (level 1) during the final scan. Therefore our paradigm allowed us to investigate how stimulus intensity is encoded within our network of interest, and how the connectivity of the different regions is modulated across the different stimulus conditions. Our result is in favor of serial mode of somatosensory processing with thalamocortical input to S1 contralateral to stimulation site. Thus our results implicates that pain information is propogated from S1 contralateral through our network of interest comprising of bilateral S1 and S2. Our analysis indicates that S1→S2 connection is modulated by pain, which suggests that S2 is higher on the hierarchy of pain processing than S1, in accordance with previous neurophysiological and MEG findings. Lastly, our analysis provides evidence for the entrance of somatosensory information into the hemisphere contralateral to the stimulation side, with inter-hemispheric connections responsible for the transfer of information to the ipsilateral hemisphere.

DISSOCIAZIONE CONSAPEVOLE-INCONSAPEVOLE NELLA PERCEZIONE VISIVA: INDIZI DA PAZIENTI EMIANOPTICI. Lesioni lungo la via visiva producono difetti caratteristici nel campo visivo. Il tipo più comune di disturbo del campo visivo omonimo (HVFD) è l’emianopsia. La probabilità del verificarsi di HVFDs in seguito ad ictus, trauma o intervento è elevata, circa il 20-30 %. Nei pazienti con HVFDs sono seriamente compromesse le attività quotidiane a causa della disabilità acquisita in nell’orientamento visivo e di esplorazione spaziale. Il recupero della funzione visiva è possibile, ma è raramente completo. Tuttavia, negli anni settanta del secolo scorso Poeppel et al e successivamente Weiskrantz et al hanno descritto la presenza di comportamento guidato dalla visione nel campo cieco di pazienti emianopsici (“blindsight”). Questa Tesi è incentrata sul tentativo di gettare nuova luce su questo importante fenomeno. In particolare, lo scopo del presente progetto di ricerca è molteplice: i) si propone di studiare le implicazioni del concetto di numerosità e di percezione Gestaltica nei normali e il ruolo di queste caratteristiche nel fenomeno del Blindsight in pazienti con emianopsia ; ii) vuole indagare le proprietà psicofisiche della visione residua (consapevole e inconsapevole) nel campo cieco e iii ) si propone di studiare l'anatomia e la funzionalità degli emisferi intatti e danneggiati attraverso l’uso dell’elettroencefalografia e della neuroimmagine funzionale. Nel primo progetto, abbiamo impiegato il paradigma di ridondanza del segnale (RSE), in soggetti normali ed in pazienti emianopsici, al fine di indagare le caratteristiche percettive dell’emicampo intatto e cieco, e l'interazione tra loro. Come prima cosa, abbiamo testato 18 partecipanti sani (età media : 31.1 ) per osservare se la RSE aumenta con 4 vs 1 stimoli. Abbiamo usato due differenti configurazioni di stimoli, nella prima i quattro stimoli formano una figura gestalt simile a una forma di diamante, mentre nell'altra la posizione degli stimoli è stata randomizzata. Ai partecipanti era richiesto di mantenere la fissazione su un piccolo stimolo centrale e, dopo l’arrivo di un segnale acustico, dovevano premere un pulsante il più rapidamente possibile alla presentazione degli stimoli visivi. I risultati hanno mostrato un aumento della RSE (cioè più rapidi tempi di reazione) quando gli stimoli erano quadrupli rispetto a quando erano singoli, indipendentemente dalla configurazione proposta. Un’ulteriore analisi ha mostrato che l’RSE con stimoli semplici e con stimoli che formano una configurazione Gestaltica è spiegata da una coattivazione neurale, piuttosto che da una teoria probabilistica, in quanto si osserva una violazione del modello di Miller. Al contrario, il risultato ottenuto nella presentazione di stimuli quadrupli in posizione randomizzata potrebbe essere spiegabile alla luce di una teoria probabilistica. Nella seconda parte, abbiamo studiato se tale paradigma modificato era più efficace nel rilevare il fenomeno del Blindsight (un comportamento inconscio guidato visivamente) in pazienti emianoptici e nei pazienti emisferectomizzati. Abbiamo testato sei pazienti con emianopsia (età media : 45,83 ) a seguito di lesione del tratto corticale o ottico e un paziente emisferectomizzato. La procedura era la stessa dell’esperimento precedente. I risultati hanno mostrato una maggiore efficacia del metodo con stimoli numerosi, tenendo conto della misurazione della RSE con più stimoli presentati contemporaneamente nell’emicampo intatto e cieco rispetto alla presentazione singola nel campo intatto. È interessante notare che la RSE nei pazienti era più pronunciata per la configurazione gestaltica. Inoltre i risultati osservati con l’analisi di risonanza magnetica funzionale hanno mostrato un'attivazione di aree visive localizzate a livello della via visiva ventrale. Nel secondo progetto, ci siamo proposti di capire quale dei due emisferi media il comportamento guidato visivamente dopo la presentazione di stimoli nell’emicampo cieco di pazienti con emianopsia. Abbiamo testato 9 pazienti (età media : 44.5 ) con il paradigma di Poffenberger ( PP ): si tratta di un compito di Tempo di Reazione che prevede la presentazione dello stimolo visivo lateralizzato e una risposta unimanuale. I risultati hanno mostrato che nell’emicampo intatto tutti i pazienti mostrano una CUD positiva (cioè normale) mentre i risultati nell’emicampo cieco erano più variabili con una CUD positiva in alcuni pazienti e negativa in altri. Quest’ultimo dato significa che la risposta nel campo cieco era mediata dall’emisfero intatto e questo potrebbe essere correlato alla estensione delle singole lesioni. Inoltre, abbiamo usato un nuovo metodo per indagare il Blindsight, abbiamo confrontato le frequenze di distribuzione cumulative (CDF) dei temi di reazione a seguito della presentazione dello stimolo nel campo intatto e cieco in condizioni normali e con gli occhi chiusi. Abbiamo testato 6 pazienti di cui due mostrano il fenomeno del blindsight mentre ad occhi chiusi non c’erano risposte sopra al caso. Infine, abbiamo usato la risonanza magnetica funzionale (fMRI) per valutare il coinvolgimento delle specifiche strutture cerebrali in IT delle informazioni visuo-motorie e il ruolo dell’emisfero intatto. Abbiamo testato il ben noto paziente con blindsight GY con il paradigma di Poffenberger . I risultati comportamentali hanno registrato una CUD positiva quando il paziente era stimolato visivamente nel campo intatto, e una CUD negativa quando stimolato nel campo cieco, suggerendo che sia l'emisfero intatto a mediare il blindsight. I risultati dell’analisi funzionale hanno mostrato l'attivazione di aree corticali (aree visive ventrali , aree visive dorsali, aree senso- motorie e premotorie) e le aree del corpo calloso, differenziato nella condizione di stimolazione consapevole e inconsapevole (anteriore vs medio -posteriore, rispettivamente). Nel terzo progetto, abbiamo misurato la risposta elettrofisiologica alla stimolazione visiva del campo visivo cieco e intatto sempre nel paradigma di Poffenberger (PP) in 12 soggetti sani e in tre pazienti emianoptici. Lo scopo dell'indagine è stato quello di indagare sulla natura e la funzionalità dell'emisfero leso, così come cercare di capire l'efficienza della trasmissione inter-emisferica. In entrambi gli emisferi abbiamo trovato una assenza di risposta ERP per la stimolazione del campo cieco mentre per la stimolazione dell’ emicampo intatto abbiamo trovato una buona risposta diretta nell'emisfero controlaterale. È interessante notare una risposta differente nei tre pazienti per la risposta commissurale indiretta. Infatti, la risposta registrata nell'emisfero lesionato è assente o molto debole in siti posteriori per il paziente EA e il paziente PC, mentre per la paziente SL la risposta registrata nell'emisfero leso era paragonabile a quella dei soggetti sani. Ciò sembrerebbe suggerire che il trasferimento interemisferico e l'integrazione di informazioni visive tra l’emisfero danneggiato e quello intatto dei pazienti emianoptici sembra avvenire nella fase percettiva e necessita dell'integrità funzionale e anatomica dello splenium del Corpo Calloso. In breve, l’interesse dell’intera ricerca è multiplo. In primo luogo, utilizzando il RSE si è constatato che vi è una sostanziale interazione tra i due emisferi nei pazienti e che la visione inconscia è sensibile alla numerosità e mostra una sorta di organizzazione percettiva gestaltica. In secondo luogo, ho descritto i risultati di un nuovo metodo per registrare la presenza di abilità residue di rilevamento di stimoli inconsci nei pazienti emianoptici, probabilmente innescato da antiche aree evolutive sottocorticali. Infine, utilizzando il paradigma di Poffenberger, con l’uso delle registrazioni ERP e della neuroimmagine, è stato possibile avere indizi utili a capire l'importanza dell'emisfero intatto nella mediazione della visione cieca.
CONSCIOUS – UNCONSCIOUS DISSOCIATIONS IN VISUAL PERCEPTION: CLUES FROM HEMIANOPIC PATIENTS. Lesions along the visual pathway produce characteristic gaps in the visual field. The most common type of homonymous field disorder (HVFD) is hemianopia. The probability of occurrence of HVFDs following a stroke, trauma or surgery is high, around 20-30%. Patients with HVFDs are seriously impaired in everyday activities and this is because of the acquired disability in visual orienting and exploration. Recovery of visual function is possible but is rarely complete. However, in the seventies of last century it has been shown by Poeppel et al. and subsequently by Weiskrantz et al. that some hemianopic patients retain some form of visually guided behaviour in the blind hemifield in absence of perceptual awareness (“blindsight”). This Thesis is mainly based on casting new light on this intriguing phenomenon. In particular, the purpose of the present research project is multifold: i) To investigate whether higher-order perceptual effects like Numerosity detection and Gestalt phenomena are present in the blind hemifield of hemianopic patients; ii) To investigate the basic psychophysical properties of conscious as well as unconscious (blindsight) residual vision in the blind field and iii) To study the anatomy and functionality of the intact and damaged hemispheres through electrophysiological recordings and functional imaging. In the first project, we employed a redundant signal effect (RSE) paradigm, in healthy participants and in patients, to investigate the perceptual characteristics of the intact and blind hemifield, and the interaction between them. Initially, we tested in healthy participants whether the RSE increases with 4 vs 1 stimuli. We used two different configurations of stimuli, in one the four redundant stimuli formed a gestalt-like figure in the shape of a diamond, while in the other the position of stimuli was randomized. We tested 18 participants (mean age: 31.1). They were required to keep their fixation steady on a central fixation point and, following onset of an acoustic warning signal, to press a button as quickly as possible upon presentation of the visual stimuli. Results showed an increase of the RSE (i.e. faster reaction times) with four with respect to single stimuli independently from the configuration proposed. The analysis of the present data showed that the RSE effect in the Single bilateral presentation and in the Quadruple Gestalt bilateral presentation is attributable to neural coactivation rather than probability summation, in that there was a violation of Miller’s race inequality. Conversely, the result obtained in the Quadruple Random bilateral presentation was attributable to a probability summation, in that there was no violation of the race inequality. In the second part of this project, we investigated if this procedure was more likely to increase the probability to detect blindsight in hemianopic patients and in hemisperectomized patients. We tested six patients with hemianopia (mean age: 45.83) as a result of cortical or optic tract lesion and one hemisperectomized patient. The procedure and design were the same as in the previous experiment. The results showed a trend toward an increase of speed of reaction time as measured by the RSE with multiple stimuli presented simultaneously to the intact and blind hemifield in comparison to stimuli to the intact field only. It is interesting to point out that the RSE in hemianopics and in the hemisperectomized patient was more pronounced for the gestalt-like configuration and this suggests the presence of gestalt-like perception in blindsight and provides important clues for rehabilitation. Moreover the functional magnetic resonance imaging results showed as expected an activation of visual areas localized at the level of the ventral visual pathway. In the second project, we tried to understand which of the two hemispheres mediates visually guided behavior following stimulus presentation to the blind hemifield of patients with hemianopia. We tested 9 patients (mean age:44.5) with the Poffenberger paradigm (PP): a RT task that involves a lateralized visual stimulus presentation in the intact and in the blind hemifield and a unimanual response. The crossed-uncrossed difference (CUD), a behavioural estimate of callosal interhemispheric transfer (IT) time for stimuli presented to the intact hemifield of all patients was positive and this can be interpreted as related to the lesioned hemisphere subserving the response whilst in the blind hemifield the results were more variable with some patients showing a positive and others a negative CUD (i.e. the response was subserved by the intact hemisphere) and this could be related to the extension of the individual lesions. In the second part, we used a new method for testing blindsight, namely to compare the cumulative distribution frequency (CDF) of RT for stimulus presentation to the intact and the blind field under normal or occluded viewing conditions. We tested 6 patients and the results were that two of them showed blindsight. We also used functional magnetic resonance (fMRI) to assess the involvement of specific brain structures in the IT of visuomotor information and the role of the intact hemisphere. We tested with the Poffenberger paradigm the well known blindsight patient GY. Behavioural results showed a positive CUD for the stimulation of the intact hemifield, and a negative CUD for the stimulation of the blind hemifield, suggesting that the intact hemisphere mediates the blindsight responses. Functional results showed activation of cortical areas (ventral visual areas, dorsal visual areas, sensori-motor and premotor areas) and callosal areas, with interesting differences in the conscious and unconscious conditions (anterior vs. middle-posterior, respectively). In the third project, we measured the electrophysiological response to visual stimulation of blind and intact visual field in the Poffenberger Paradigm (PP) in 12 healthy subjects and in three hemianopic patients. The purpose of the investigation was to inquire into the nature and the functionality of the lesioned hemisphere as well as try to understand the efficiency of IT. In both hemispheres we found an absence of ERP responses for stimulation of the hemianopic field while for stimulation of the intact hemifield we found a good direct response in the contralateral hemisphere. Interestingly, we observed a different response in the three patients for the indirect commissural response: the response recorded in the lesioned hemisphere was absent or very weak in posterior sites for patient EA and patient PC while for patient SL the response recorded in the lesioned hemisphere was comparable to that of healthy participants. This suggests that IT and integration of visual information from the intact to the damaged hemisphere of hemianopic patients seems to occur at the perceptual stage depending on the functional and anatomical integrity of the splenium of the CC. In short, the thrust of this entire Thesis is multifold. First, by using the Redundant Signal Effect it was found that there is a substantial cross-talk between the two hemispheres in hemianopic patients, including one hemispherectomy patient, and that unconscious vision is sensitive to stimulus numerosity and shows a sort of gestaltic perceptual organization. Second, I described the results of a new method to assess a reliable detection of unconscious stimuli in hemianopic patients probably triggered by evolutionary ancient subcortical areas. Finally, by using the Poffenberger paradigm, associated or not with ERP recordings, it was possible to have clues as to the importance of the intact hemisphere in mediating blindsight.