Exploring the neurobiology of reading through non-invasive brain stimulation: A review

Non-invasive brain stimulation (NIBS) has gained increasing popularity as a modulatory tool for drawing causal inferences and exploring task-specific network interactions. Yet, a comprehensive synthesis of reading-related NIBS studies is still missing. We fill this gap by synthesizing the results of 78 NIBS studies investigating the causal involvement of brain regions for reading processing, and then link these results to a neurobiological model of reading. The included studies provide evidence for a functional-anatomical double dissociation for phonology versus semantics during reading-related processes within left inferior frontal and parietal areas. Additionally, the posterior parietal cortex and the anterior temporal lobe are identified as critical regions for reading-related processes. Overall, the findings provide some evidence for a dual-stream neurobiological model of reading, in which a dorsal stream (left temporo-parietal and inferior frontal areas) processes unfamiliar words and pseudowords, and a ventral stream (left occipito-temporal and inferior frontal areas, with assistance from the angular gyrus and the anterior temporal lobe) processes known words. However, individual differences in reading abilities and strategies, as well as differences in stimulation parameters, may impact the neuromodulatory effects induced by NIBS. We emphasize the need to investigate task-specific network interactions in future studies by combining NIBS with neuroimaging

Early and Sustained Supramarginal Gyrus Contributions to Phonological Processing

Reading is a difficult task that, at a minimum, requires recognizing a visual stimulus and linking it with its corresponding sound and meaning. Neurologically, this involves an anatomically distributed set of brain regions cooperating to solve the problem. It has been hypothesized that the supramarginal gyrus (SMG) contributes preferentially to phonological aspects of word processing and thus plays an important role in visual word recognition. Here, we used chronometric transcranial magnetic stimulation (TMS) to investigate the functional specificity and timing of SMG involvement in reading visually presented words. Participants performed tasks designed to focus on either the phonological, semantic, or visual aspects of written words while double pulses of TMS (delivered 40 ms apart) were used to temporarily interfere with neural information processing in the left SMG at five different time windows. Stimulation at 80/120, 120/160, and 160/200 ms post-stimulus onset significantly slowed subjects’ reaction times in the phonological task. This inhibitory effect was specific to the phonological condition, with no effect of TMS in the semantic or visual tasks, consistent with claims that SMG contributes preferentially to phonological aspects of word processing. The fact that the effect began within 80–120 ms of the onset of the stimulus and continued for approximately 100 ms, indicates that phonological processing initiates early and is sustained over time. These findings are consistent with accounts of visual word recognition that posit parallel activation of orthographic, phonological, and semantic information that interact over time to settle into a distributed, but stable, representation of a word

Occipito-temporal contributions to reading

The debate regarding the role of ventral occipito-temporal cortex (vOTC) in visual word recognition arises in part from difficulty delineating the functional contributions of vOTC as separate from other areas of the reading network. Successful transcranial magnetic stimulation (TMS) of the area could provide a novel source of information regarding the area’s function, by offering the possibility of temporarily, non-invasively perturbing its information processing and assessing the consequences on behaviour. However, the area is often considered too deep to successfully stimulate with TMS. Thus the initial step was the demonstration of the feasibility of stimulation, which I proved in the first series of experiments. The stimulation resulted in a disruption in visual word recognition that was stimulus- and site- specific. The second series of experiments further investigated the stimulus-specificity, demonstrating that the nature of this specificity was task-dependent. The final series of TMS experiments in the thesis utilised the high temporal resolution of TMS to map out the dynamics of processing in both left and right vOTC, revealing hemispheric asymmetries in the time course of ventral occipito-temporal processing consistent for both visual words and objects. To complete these experiments, I acquired a large amount of functional localiser data for neuronavigated TMS. This allowed the investigation of the effectiveness of fMRI localisation for TMS and in addition the investigation of the important issue of how consistent the functional regions of interest (fROI) produced by these scans are. The first of two experiments showed these fROIs may have surprisingly poor reliability while the second investigated how best they can be optimised, maximising reliability. In conclusion, my PhD has demonstrated the feasibility and potential of using TMS to investigate vOTC contributions to visual word and object recognition, providing a novel source of information capable of informing the ongoing debate concerning vOTC

The role of the left inferior parietal lobule in reading.

One of the regions that have consistently been included in the neurological models of reading is the left inferior parietal lobule (IPL), however, the precise functional and temporal contributions of this region to reading have not yet been fully established. There are three hypotheses concerning IPL contributions to visual word recognition. The first one claims that the IPL is the site of stored visual word forms although it remains unclear whether these are stored in supramarginal (SMG) or angular (ANG) fields of the IPL. The second hypothesis argues that the procedures for converting spelling-to-sound are a function of the IPL, but it is unclear whether these are specifically located in SMG or ANG, or both. Finally, a third hypothesis suggests that SMG and ANG preferentially contribute to phonological and semantic processing of written words, respectively. In this thesis, I empirically evaluated these hypotheses using repetitive transcranial magnetic stimulation (rTMS) to temporarily and selectively disrupt processing in left SMG and ANG during visual word recognition and measure the effect on reading behaviour. I also investigated the time course of SMG and ANG involvement to visual word recognition using double-pulse TMS. My research demonstrates that SMG contributes preferentially to phonological aspects of word processing and the processing begins early and over a sustained period of time (between 80 to 200 msec post-stimulus onset). ANG contributes preferentially to semantic aspects of word processing but the temporal dynamics of this contribution were not successfully revealed in this thesis and require further investigation. In addition, I empirically evaluated the efficiency of using functional magnetic resonance (fMRI) and TMS to functionally localize a target site for TMS experiments. I demonstrated that both methods are similarly accurate in identifying stimulation site but neither of them is 100% accurate

Adaptive plasticity in the healthy reading network investigated through combined neurostimulation and neuroimaging

The reading network in the human brain comprises several regions, including the left inferior frontal cortex (IFC), ventral occipito-temporal cortex (vOTC) and dorsal temporo-parietal cortex (TPC). The left TPC is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings. Here, we tested the causal contribution of this area for reading with repetitive transcranial magnetic stimulation (rTMS) and explored the response of the reading network using functional magnetic resonance imaging (fMRI). 28 healthy adult readers overtly read simple and complex words and pseudowords during fMRI after effective or sham TMS over the left TPC. Behaviorally, effective stimulation slowed pseudoword reading. A multivariate pattern analysis showed a shift in activity patterns in the left IFC for pseudoword reading after effective relative to sham TMS. Furthermore, active TMS led to increased effective connectivity from the left vOTC to the left TPC, specifically for pseudoword processing. The observed changes in task-related activity and connectivity suggest compensatory reorganization in the reading network following TMS-induced disruption of the left TPC. Our findings provide first evidence for a causal role of the left TPC for overt pseudoword reading and emphasize the relevance of functional interactions in the healthy reading network for successful pseudoword processing

The cognitive and neural basis of developmental prosopagnosia

Developmental prosopagnosia (DP) is a severe impairment of visual face recognition in the absence of any apparent brain damage. The factors responsible for DP have not yet been fully identified. This article provides a selective review of recent studies investigating cognitive and neural processes that may contribute to the face recognition deficits in DP, focusing primarily on event-related brain potential (ERP) measures of face perception and recognition. Studies that measured the face-sensitive N170 component as a marker of perceptual face processing have shown that the perceptual discrimination between faces and non-face objects is intact in DP. Other N170 studies suggest that faces are not represented in the typical fashion in DP. Individuals with DP appear to have specific difficulties in processing spatial and contrast deviations from canonical upright visual-perceptual face templates. The rapid detection of emotional facial expressions appears to be unaffected in DP. ERP studies of the activation of visual memory for individual faces and of the explicit identification of particular individuals have revealed differences between DPs and controls in the timing of these processes and in the links between visual face memory and explicit face recognition. These observations suggest that the speed and efficiency of information propagation through the cortical face network is altered in DP. The nature of the perceptual impairments in DP suggests that atypical visual experience with the eye region of faces over development may be an important contributing factor to DP

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived “virtual lesion.” Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading

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

Dissociating the functions of superior and inferior parts of the left ventral occipito-temporal cortex during visual word and object processing

During word and object recognition, extensive activation has consistently been observed in the left ventral occipito-temporal cortex (vOT), focused around the occipito-temporal sulcus (OTs). Previous studies have shown that there is a hierarchy of responses from posterior to anterior vOT regions (along the y-axis) that corresponds with increasing levels of recognition - from perceptual to semantic processing, respectively. In contrast, the functional differences between superior and inferior vOT responses (i.e. along the z-axis) have not yet been elucidated. To investigate, we conducted an extensive review of the literature and found that peak activation for reading varies by more than 1 cm in the z-axis. In addition, we investigated functional differences between superior and inferior parts of left vOT by analysing functional MRI data from 58 neurologically normal skilled readers performing 8 different visual processing tasks. We found that group activation in superior vOT was significantly more sensitive than inferior vOT to the type of task, with more superior vOT activation when participants were matching visual stimuli for their semantic or perceptual content than producing speech to the same stimuli. This functional difference along the z-axis was compared to existing boundaries between cytoarchitectonic areas around the OTs. In addition, using dynamic causal modelling, we show that connectivity from superior vOT to anterior vOT increased with semantic content during matching tasks but not during speaking tasks whereas connectivity from inferior vOT to anterior vOT was sensitive to semantic content for matching and speaking tasks. The finding of a functional dissociation between superior and inferior parts of vOT has implications for predicting deficits and response to rehabilitation for patients with partial damage to vOT following stroke or neurosurgery