Nature of crossmodal plasticity in the blind brain and interplay with sight restoration

Thèse réalisée en cotutelle avec l'Université catholique de Louvain.Ce travail de thèse s’est intéressé à la plasticité cérébrale associée à la privation/restauration visuelle. A travers deux études transversales utilisant l’imagerie par résonance magnétique fonctionnelle auprès d’un groupe de participants présentant une cécité congénitale ou précoce (ainsi qu’auprès d’un groupe contrôle de participants voyants), nous avons tenté de caractériser la manière dont le cortex occipital - typiquement dédié au traitement de l’information visuelle - se réorganise afin de traiter différents stimuli auditifs. Nous démontrons qu’en cas de cécité précoce, différentes régions du cortex occipital présentent une préférence fonctionnelle pour certains types de stimuli non-visuels, avec une spécialisation fonctionnelle qui respecte celle de régions typiquement impliquées dans le traitement d’informations similaires en vision. Ces découvertes constituent une avancée conceptuelle concernant le rôle joué par les contraintes intrinsèques d’une part, et par l’expérience d’autre part, dans l’émergence de réponses sensorielles et fonctionnelles du cortex occipital. D’une part, l’observation de réponses occipitales à la stimulation auditive chez le non-voyant précoce (réorganisation transmodale) rend compte de la capacité du cortex occipital à réorienter sa modalité sensorielle préférentielle en fonction de l’expérience. D’autre part, l’existence de modules cognitifs spécialisés dans le cortex occipital du non-voyant précoce, semblables à ceux du cerveau voyant, démontre les contraintes intrinsèques imposées à une telle plasticité. Dans une étude de cas longitudinale, nous avons également exploré comment les changements plastiques associés à la cécité interagissent avec une récupération visuelle partielle à l’âge adulte. Nous avons réalisé des mesures pré et post-opératoires auprès d’un patient ayant récupéré la vision, en combinant les techniques comportementales ainsi que de neuroimagerie fonctionnelle et structurelle afin d’investiguer conjointement l’évolution de la réorganisation transmodale et de la récupération des fonctions visuelles à travers le temps. Nous démontrons que les changements structurels et fonctionnels caractérisant le cortex occipital du non-voyant sont partiellement réversibles suite à une récupération visuelle à l’âge adulte. De manière générale, ces recherches témoignent de l’importante adaptabilité du cortex occipital aux prises avec des changements drastiques dans l’expérience visuelle.The present Ph.D. work was dedicated to the study of experience-dependent brain plasticity associated with visual deprivation/restoration. In two cross-sectional studies involving the use of functional magnetic resonance imaging in a group of participants with congenital or early blindness (and in a control group of sighted participants), we attempted to characterize the way the occipital cortex - typically devoted to vision – reorganizes itself in order to process different auditory stimuli. We demonstrate that in case of early visual deprivation, distinct regions of the occipital cortex display a functional preference for specific non-visual attributes, maintaining a functional specialization similar to the one that characterizes the sighted brain. Such studies have shed new light on the role played by intrinsic constraints on the one side, and experience on the other, in shaping the modality- and functional tuning of the occipital cortex. On the one hand, the observation of occipital responses to auditory stimulation (crossmodal plasticity) highlights the ability of the occipital cortex to reorient its preferential tuning towards the preserved sensory modalities as a function of experience. On the other hand, the observation of specialized cognitive modules in the occipital cortex, similar to those observed in the sighted, highlights the intrinsic constraints imposed to such plasticity. In a longitudinal single-case study, we further explored how the neuroplastic changes associated with blindness may interact with the newly reacquired visual inputs following partial visual restoration in adulthood. We performed both pre- and post-surgery measurements in a sight-recovery patient combining behavioral, neurostructural and neurofunctional methods in order to jointly investigate the evolution of crossmodal reorganization and visual recovery across time. We demonstrate that functional and structural changes evidenced in the visually-deprived occipital cortex can only partially reverse following sight restoration in adulthood. Altogether, our findings demonstrate the striking adaptability of the occipital cortex facing drastic changes in visual experience

Form in Darkness: Linking Visual Cortex Structure With Spontaneous Neural Function

Spontaneous neural activity within visual cortex is synchronized at varying spatial scales, from the cytoarchitecural level of individual neurons to the coarse scale of whole regions. The neural basis of this synchronicity remains ambiguous. In this thesis, we focus on the role visual experience plays in organizing the spontaneous activity within the visual system. We start in Chapter 2 by creating a means by which to analyze homologous patches of cortex between sighted and blind individuals, as lack of vision precludes the use of traditional stimulus-driven mapping techniques. We find that anatomy alone could indeed predict the retinotopic organization of an individual\u27s striate cortex with an accuracy equivalent to the length of a typical mapping experiment. Chapter 3 applies this approach to analyze the organization of spontaneous signals within the striate cortex of blind and sighted subjects. We find that lack of visual experience produces a subtle change in the pattern of corticocortico correlations only between the hemispheres, and that these correlations are best modeled as function of cortical distance, not retinotopy. Chapter 4 expands our analysis to include areas V2 and V3. Here, we find that persistent visual experience supports network-level neural synchrony between spatially distributed cortical visual areas at both a coarse (regional) and fine (topographic) scale. Together, these results allow us model the organization of spontaneous activity in visual cortex as a combination of network signals linked to visual function and intrinsic signals coupled to structural connections. In the final chapter, we examine possible top-down mediators that may further modulate this network-level correlation. Minimal change in synchronicity is observed in a subject with a corpus callosotomy, suggesting the preeminence of bottom-up inputs. Taken together, this work advances our understanding of the origins of coherent spontaneous neural activity within visual cortex

Exploring the Structural and Functional Organization of the Dorsal Zone of Auditory Cortex in Hearing and Deafness

Recent neuroscientific research has focused on cortical plasticity, which refers to the ability of the cerebral cortex to adapt as a consequence of experience. Over the past decade, an increasing number of studies have convincingly shown that the brain can adapt to the loss or impairment of a sensory system, resulting in the expansion or heightened ability of the remaining senses. A particular region in cat auditory cortex, the dorsal zone (DZ), has been shown to mediate enhanced visual motion detection in deaf animals. The purpose of this thesis is to further our understanding of the structure and function of DZ in both hearing and deaf animals, in order to better understand how the brain compensates following insult or injury to a sensory system, with the ultimate goal of improving the utility of sensory prostheses. First, I demonstrate that the brain connectivity profile of animals with early- and late-onset deafness is similar to that of hearing animals, but the projection strength to visual brain regions involved in motion processing increases as a consequence of deafness. Second, I specifically evaluate the functional impact of the strongest auditory connections to area DZ using reversible deactivation and electrophysiological recordings. I show that projections that ultimately originate in primary auditory cortex (A1) form much of the basis of the response of DZ neurons to auditory stimulation. Third, I show that almost half of the neurons in DZ are influenced by visual or somatosensory information. I further demonstrate that this modulation by other sensory systems can have effects that are opposite in direction during different portions of the auditory response. I also show that techniques that incorporate the responses of multiple neurons, such as multi-unit and local field potential recordings, may vastly overestimate the degree to which multisensory processing occurs in a given brain region. Finally, I confirm that individual neurons in DZ become responsive mainly to visual stimulation following deafness. Together, these results shed light on the function and structural organization of area DZ in both hearing and deaf animals, and will contribute to the development of a comprehensive model of cross-modal plasticity

Intégration et topographie fonctionnelles : l'influence de la cécité précoce

L’organisation fonctionnelle du cerveau humain montre une similarité interindividuelle remarquable et robuste, suggérant que sa structure fonctionnelle est innée. Cependant, cette observation n’est pas sans équivoques, le cerveau est aussi plastique : son organisation peut être influencée par des évènements survenant tôt dans la vie. Parmi les plus marquants, on retrouve la perte de vision précoce ou congénitale. En effet, il a été démontré à plusieurs reprises que, chez les personnes non-voyantes, les régions habituellement dédiées à la vision (ex. : lobes occipitaux) se réorganisent afin d’analyser des stimuli auditifs et tactiles. Les plus récentes études chez les non-voyants se sont intéressées à la relation entre la réorganisation des lobes occipitaux et les deux principes organisateurs fondamentaux du cerveau : la localisation fonctionnelle et l’intégration fonctionnelle. Le premier signifie que des fonctions spécifiques mobilisent des régions circonscrites du cerveau, tandis que le second signifie que les régions du cerveau communiquent entre elles afin de créer un tout cohérent. Toutefois, l’ampleur de l’effet de la cécité sur l’organisation du cerveau est encore inconnue. Premièrement, la topographie de modules possédant une fonction spécifique n’a encore jamais fait l’objet d’un examen direct, approfondi et holistique chez les non-voyants, et ce, malgré le fait qu’il s’agisse d’une caractéristique clef de la localisation fonctionnelle. En outre, les études examinant l’intégration fonctionnelle chez les non-voyants semblent en contradiction avec celles qui l’étudient de manière indirecte. Cette dépendance des résultats sur la méthode employée nécessite une étude approfondie des éléments influençant ces résultats afin que des conclusions appropriées puissent être tirées. Ainsi, bien que la plasticité cérébrale chez les personnes non-voyantes fasse l’objet de plusieurs études, son influence sur l’organisation fonctionnelle du cerveau reste à approfondir et est sujette à débats. De ces faits, l’objectif principal de la présente thèse est d’examiner l’influence de la cécité précoce sur la topographie des modules fonctionnels ainsi que sur l’intégration fonctionnelle. Pour cela, trois expériences distinctes ont été conduites. La première expérience a été élaborée afin de comparer la disposition spatiale des modules fonctionnels des voyants à celle des non-voyants. À cette fin, une méthode a été développée qui permettait d’examiner la question de manière holistique et sans biais à partir de données d’imagerie par résonance magnétique. Les résultats indiquent que seules les régions « visuelles » de bas niveau, les pôles occipitaux, sont sous-divisées de manière différente chez les personnes non-voyantes. À l’opposé, les régions de haut niveau maintiennent leur disposition spatiale. Ceci suggère que l’établissement de modules fonctionnels au sein du lobe occipital dépend à la fois d’entrées sensorielles visuelles, ainsi que du niveau hiérarchique de la région. La seconde expérience de cette thèse visait à examiner certains facteurs qui pourraient causer les contradictions observées par les études sur l’intégration fonctionnelle chez les non-voyants. Les données d’une des méthodes employées pour mesurer l’intégration fonctionnelle, l’état de repos mesuré par imagerie par résonance magnétique fonctionnelle, ont été comparées à celles obtenues lorsque les participants se concentraient sur une tâche auditive. D’abord, les résultats démontrent une dépendance de l’intégration fonctionnelle sur l’état cognitif des participants, suggérant que les différences entre non-voyants et voyants observées jusqu’ici doivent être interprétées prudemment. De plus, et d’une importance inédite, les résultats démontrent que les pôles occipitaux possèdent des caractéristiques fonctionnelles différentes chez les non-voyants que chez les voyants. Ces caractéristiques suggèrent que les pôles sont impliqués dans un nombre plus important de réseaux chez les personnes non-voyantes. La troisième expérience de cette thèse a été conçue pour faire suite aux résultats des deux premières. Spécifiquement, elle valide une méthode qui sera employée afin d’examiner des régions qui, selon les deux premières expériences de cette thèse, possédaient des caractéristiques fonctionnelles réorganisées chez les personnes non-voyantes : les pôles occipitaux. Cette méthode, développée afin de contrôler la difficulté d’une tâche de perception de voix humaines, s’est avérée valide. Ainsi, elle pourra être employée lors d’études futures afin de désambiguïser la fonction des pôles occipitaux chez les non-voyants. De plus, les résultats de l’expérience révèlent plusieurs mécanismes d’action sous-jacents la perception de voix chez l’être humain. Globalement, les deux premières expériences constituant cette thèse mettent en évidence les caractéristiques fonctionnelles réorganisées au sein des pôles occipitaux chez les PNV, une région encore sous-étudiée chez cette population. La troisième étude présente une méthode permettant d’étudier ce phénomène. Les caractéristiques dévoilées par ces expériences pavent la voie vers de nouvelles hypothèses et études qui permettront d’approfondir notre conception du cerveau et de la plasticité cérébrale.The brain’s functional organization shows a remarkable similarity across individuals suggesting that its functional structure is innate. However, this observation is not unequivocal for the brain is also plastic; its organization is subject to changes following important early life experiences. Of such event, early or congenital vision-loss features among the most outstanding. Following blindness, cerebral regions usually involved with visual analysis (e.g. occipital lobes) are reorganized to process auditory, tactile, and olfactory stimuli, as well as higher order cognitive tasks such as memory and language. Recent studies on blind individuals have focused on the relationship between the reorganization of the occipital lobes and the fundamental organizational principles of the brain: functional localization and integration. The first indicates that specific functions take place within circumscribed cerebral regions, whereas the second indicates that these regions communicate together. However, the extent to which blindness influences the brain’s organization is still unknown. First, the topography of modules possessing specific functions has yet to be the object of a direct, in depth, and holistic investigation in blind people. This is true even though module topography is a key characteristic of spatially localized functions. Moreover, studies investigating functional integration in blind individuals appear to contradict those which study integration indirectly. The dependence of results upon the method employed demands further investigation of the elements that might influence integration so that appropriate conclusions can be drawn. Thus, even though blindness-induced brain plasticity has been the object of multiple studies, its influence upon cerebral organization is partly subject to debate, and must be further defined. Accordingly, the main objective of this thesis was to study the influence of early blindness upon the topography of functional modules and upon functional integration. In order to do so, three distinct experiments were carried. The first experiment was conceived so as to compare the spatial topographies of functional modules across blind and sighted participants. To this end, a holistic and bias-free method, which made use of resting-state functional magnetic resonance imagery, was developed. Results indicate that only blind people’s occipital poles possess modules which were topographically different from those found in sighted individuals whereas higher level “visual” areas do not show this effect. This suggests that the formation of functional modules within the “visual” cortices depends on both sensory inputs as well as the hierarchical level of a region. The second experiment of this thesis examined factors which might cause the contradictions observed by studies on blind people’s functional integration. Data obtained from a method devised to measure functional integration, resting-state functional magnetic resonance imagery, were compared to those obtained while participant focused on auditory stimuli. Results are twofold. First, results showed that group differences in functional integration vary as a function of the participant’s cognitive states, suggesting that differences in functional integration observed using resting-state fMRI should be interpreted with caution. Second, our results reveal novel findings pertaining to the occipital poles of blind people; these regions showed strikingly different characteristic following early visual loss which are suggestive of their role in a multitude of networks. The third experiment of this thesis was designed following the first two. Specifically, it validates a method to examine the functions of blind people’s occipital poles, a region which had been shown to possess reorganized functional characteristics by the first two experiments of this thesis. A new methodology was designed to control the difficulty of a voice discrimination task, showing its validity. Thus, it will be possible to use it in future studies to investigate the function of the occipital lobes in blind people. Furthermore, results from the experiment revealed multiple mechanisms which might underlie voice perception in humans. Overall, the experiments forming this thesis evidence a reorganisation of the occipital poles’ functional characteristics in early-blind individuals. Additionally, they provide methods needed to investigate the functions of this understudied region. Most importantly, the observation that blind people’s occipital poles show modified functional characteristics paves the way to new hypotheses and studies which will allow to further investigate and deepen our understanding of the human brain and its plasticity

Investigating Neural Substrates of Visual Motion Sensitivity in Deaf Individuals

The aim of this thesis has been to explore neural substrates of enhanced far-peripheral visual motion processing in congenitally deaf adults. To do this, psychophysical measures were used as well as novel fMRI stimulus delivery methods to record responses to stimu- lation in the far-peripheral visual field. For the first time, far-peripheral visual field mapping measured an extended representa- tion of the visual field (72 ◦) in early visual cortex in deaf and hearing individuals. Using this method, unique evidence of plasticity within the cortical surface area distribution of visual field representations in the primary visual cortex was found in congenitally deaf adults, biased towards the far-peripheral visual field. Furthermore, neural responses to far-peripheral stimuli were measured in visual motion processing areas V5/MT+ and V6, and in auditory regions. Results show novel and dis- tinctive differences in response profiles in auditory, but not visual regions between deaf and hearing participants, indicating crossmodal plasticity in deaf participants, specific to coherent but not incoherent global optic flow field motion stimuli. Most importantly, the aim of the thesis was to relate neural measures to behavioural per- formance of motion perception. The results show evidence that unimodal plasticity in V1 and activation in visual motion areas V5/MT+ and V6 are not related to performance in two visual motion tasks (local motion detection and global motion direction discrimina- tion), but that response inhibition and excitation levels in auditory regions are related to motion processing performance in deaf and hearing individuals. In summary, the findings described in this thesis show for the first time that congenital deafness leads to plastic changes within primary visual cortex. In addition, auditory but not visual motion regions are recruited differentially between deaf and hearing individu- als, depending on the motion type, and this activation shows a trending relationship with visual motion performance in both groups

The brain as image processor and generator:towards function-restoring brain-computer-interfaces

As neuroscientists are slowly unraveling the mysteries of the brain, neurotechnology like brain-computer-interfaces (BCIs) might become a new standard for medical applications in those with brain injuries. BCIs allow for direct communication between the brain and a device, and could potentially restore links that are broken due to brain damage. In addition, a better understanding of the human mind and its mechanisms could greatly boost the success of these devices. This dissertation features (high-field) functional magnetic resonance imaging (fMRI) to study human cognitive functioning, as fMRI allows for studying the brain of living humans in great spatial detail. Firstly, the dissertation describes how well brain regions that are important for visual perception can be located between individuals. Some of these regions are in part responsible for recognizing objects like faces, bodies, places and motion. Secondly, differences in functional organization of the brain were explored between individuals by simulating the placement of a visual cortical prosthesis. Such a prosthesis can bypass the (broken) connections between the eye and brain in blind people, and potentially restore a rudimentary form of vision. Finally, new techniques were presented that show that visual perception and mental imagery are closely related, and allow for reading letter shapes directly from the mind. Together, this dissertation adds new foundations for the development of neurotechnological applications

Functional and anatomical properties of visual cortex in individuals with congenital loss of cone photoreceptor function and normally sighted controls

The aim of this thesis was to systemically assess reported cortical reorganisation in achromatopsia, a congenital loss of cone photoreceptor function, to inform the current development of vision restoration approaches. Both, functional and structural magnetic resonance imaging (MRI) were used to answer if and to what extend the brain undergoes changes when visual input is lost from birth. First, visual cortical representations of rod and cone driven signals were examined in normally sighted participants to detail differences between these two retinal pathways. We showed that spatial summation properties of the rod pathway are expressed at a cortical level and highlighted that low light levels mainly affect primary visual cortex, while extra striate areas, likely related to their increased spatial pooling properties, still show robust responses. Further, functional MRI showed no differences in cortical responses at central visual field representations between achromats and controls, while achromats that presented with reduced rod function are characterised by a more severe reduction in cortical responses. Notably, traces of remapping in form of an eccentricity shift cannot be ruled out for some participants, Last, this thesis examined brain integrity in achromatopsia using surface-based morphometry and revealed that surface area is reduced across primary visual cortex. Further, patients showed highly localised thickening of the foveal representation in primary visual cortex, supporting the notion of aberrant pruning processes. In summary, findings presented in this thesis allowed insights into cortical mechanisms that maximise sensitivity when visual information is sparse and clearly showed that remapping is not a general feature in achromatopsia while the absence of visual input has distinct effects on cortical structure, comparable to other patient groups with congenital loss of vision

How the brain controls hand actions: TMS, fMRI and behavioural studies

This thesis focused on testing the predictions made in Milner and Goodale’s model and reports finding from experiments investigating how inputs from both the dorsal and the ventral streams are required when we perform hand actions with objects (Chapter 2) and tools (Chapter 3 & 4) using different paradigms such as real and pantomimed grasping and techniques such as transcranial magnetic stimulation, motion-tracking of hand movements and cutting-edge fMRI multivoxel pattern analysis. The primary aim was to gain a new insight on the role of the dorsal and the ventral visual streams in real grasping and pantomiming and to understand what specific aspects of objects and movements associated with them are represented within the two streams. The first experiment (Chapter 2) examined the causal role of the anterior intraparietal and the lateral occipital in object’s real and pantomimed grasping using TMS. The results showed that real object grasping and pantomime actions without the objects in hand require the left dorsal stream but that information from the ventral stream is additionally required for pantomiming. The experiments in Chapter 3 and 4 investigated how tools and tool related actions are represented within the dorsal and the ventral stream (Chapter 3) and whether different action end-goals affected early grasping kinematics (Chapter 4). Using MVPA we showed that both dorsal and ventral stream regions represent information about functional and structural manipulation knowledge of tools. Moreover, we showed that both streams represent tool identity, which seems in line with our behavioural findings that tool identity affects grasping kinematics. The current work provided a detailed understanding of how the dorsal and the ventral streams interact in tool processing and propose a more sophisticated view of the distributed representations across the two streams. These findings open up a number of research avenues as well as help understanding how actions are disrupted in brain-damaged patients and advance the development of neural prosthetics