Brain Plasticity associated with Predictive Masking and Glaucoma

Glaucoma is a disease resulting from damage at the optic nerve, the “highway” through which visual information travels from the retina towards the visual brain. Such lesion deprives the visual cortex of the regular input, causing interruptions within the visual field – scotoma. However, even when such lesions occur, perception remains stable as the human visual system perceptually masks the insult with the visual features of nearby regions of the visual field. To unravel the neural mechanisms by which this remarkable capacity occurs in glaucomatous individuals, we used functional magnetic resonance imaging (fMRI) and neural modelling to track changes in cortical population receptive fields (pRFs). We found that visual neurons from early visual areas (V1-3) expanded their pRFs both inside and at the vicinity of the lesion. V1 pRFs also shifted their preferred central position towards the outside of the scotoma. By doing so, neural populations were able to process information from spared visual field, consistent with the notion of predictive masking. In contrast, well-sighted observers did not show similar patterns of neural activity in response to the introduction of an artificial scotoma (AS). Our findings provide evidence of enduring cortical reorganization underlying the predictive spatial masking of scotomas in glaucoma, meeting the contemporary view that early visual areas of the adult human brain retain plastic mechanisms. Furthermore, the involvement of the brain suggests that glaucoma pathogenesis goes beyond the eye

The interaction between human vision and eye movements in health and disease

Human motor behaviour depends on the successful integration of vision and eye movements. Many studies have investigated neural correlates of visual processing in humans, but typically with the eyes stationary and fixated centrally. Similarly, many studies have sought to characterise which brain areas are responsible for oculomotor control, but generally in the absence of visual stimulation. The few studies to explicitly study the interaction between visual perception and eye movements suggest strong influences of both static and dynamic eye position on visual processing and modulation of oculomotor structures by properties of visual stimuli. However, the neural mechanisms underlying these interactions are poorly understood. This thesis uses a range of fMRI methodologies such as retinotopic mapping, multivariate analsyis techniques, dynamic causal modelling and ultra high resolution imaging to examine the interactions between the oculomotor and visual systems in the normal human brain. The results of the experiments presented in this thesis demonstrate that oculomotor behaviour has complex effects on activity in visual areas, while spatial properites of visual stimuli modify activity in oculomotor areas. Specifically, responses in the lateral geniculate nucleus and early cortical visual areas are modulated by saccadic eye movements (a process potentially mediated by the frontal eye fields) and by changes in static eye position. Additionally, responses in oculomotor structures such as the superior colliculus are biased for visual stimuli presented in the temporal rather than nasal hemifield. These findings reveal that although the visual and oculomotor systems are spatially segregated in the brain, they show a high degree of integration at the neural level. This is consistent with our everyday experience of the visual world where frequent eye movements do not lead to disruption of visual continuity and visual information is seamlessly transformed into motor behaviour

Assessment of the potentials and limitations of cortical-based analysis for the integration of structure and function in normal and pathological brains using MRI

The software package Brainvisa (www.brainvisa.tnfo) offers a wide range of possibilities for cortical analysis using its automatic sulci recognition feature. Automated sulci identification is an attractive feature as the manual labelling of the cortical sulci is often challenging even for the experienced neuro-radiologists. This can also be of interest in fMRI studies of individual subjects where activated regions of the cortex can simply be identified using sulcal labels without the need for normalization to an atlas. As it will be explained later in this thesis, normalization to atlas can especially be problematic for pathologic brains. In addition, Brainvisa allows for sulcal morphometry from structural MR images by estimating a wide range of sulcal properties such as size, coordinates, direction, and pattern. Morphometry of abnormal brains has gained huge interest and has been widely used in finding the biomarkers of several neurological diseases or psychiatric disorders. However mainly because of its complexity, only a limited use of sulcal morphometry has been reported so far. With a wide range of possibilities for sulcal morphometry offered by Brainvisa, it is possible to thoroughly investigate the sulcal changes due to the abnormality. However, as any other automated method, Brainvisa can be susceptible to limitations associated with image quality. Factors such as noise, spatial resolution, and so on, can have an impact on the detection of the cortical folds and estimation of their attributes. Hence the robustness of Brainvisa needs to be assessed. This can be done by estimating the reliability and reproducibility of results as well as exploring the changes in results caused by other factors. This thesis is an attempt to investigate the possible benefits of sulci identification and sulcal morphometry for functional and structural MRI studies as well as the limitations of Brainvisa. In addition, the possibility of improvement of activation localization with functional MRI studies is further investigated. This investigation was motivated by a review of other cortical-based analysis methods, namely the cortical surface-based methods, which are discussed in the literature review chapter of this thesis. The application of these approaches in functional MRI data analysis and their potential benefits is used in this investigation

Visual Cortex

The neurosciences have experienced tremendous and wonderful progress in many areas, and the spectrum encompassing the neurosciences is expansive. Suffice it to mention a few classical fields: electrophysiology, genetics, physics, computer sciences, and more recently, social and marketing neurosciences. Of course, this large growth resulted in the production of many books. Perhaps the visual system and the visual cortex were in the vanguard because most animals do not produce their own light and offer thus the invaluable advantage of allowing investigators to conduct experiments in full control of the stimulus. In addition, the fascinating evolution of scientific techniques, the immense productivity of recent research, and the ensuing literature make it virtually impossible to publish in a single volume all worthwhile work accomplished throughout the scientific world. The days when a single individual, as Diderot, could undertake the production of an encyclopedia are gone forever. Indeed most approaches to studying the nervous system are valid and neuroscientists produce an almost astronomical number of interesting data accompanied by extremely worthy hypotheses which in turn generate new ventures in search of brain functions. Yet, it is fully justified to make an encore and to publish a book dedicated to visual cortex and beyond. Many reasons validate a book assembling chapters written by active researchers. Each has the opportunity to bind together data and explore original ideas whose fate will not fall into the hands of uncompromising reviewers of traditional journals. This book focuses on the cerebral cortex with a large emphasis on vision. Yet it offers the reader diverse approaches employed to investigate the brain, for instance, computer simulation, cellular responses, or rivalry between various targets and goal directed actions. This volume thus covers a large spectrum of research even though it is impossible to include all topics in the extremely diverse field of neurosciences

Contextual modulations of visual perception and visual cortex activity in humans

Visual perception and neural processing depend on more than retinal stimulation alone. They are modulated by contextual factors like cross-modal input, the current focus of attention or previous experience. In this thesis I investigate ways in which these factors affect vision. A first series of experiments investigates how co-occurring sounds modulate vision, with an emphasis on temporal aspects of visual processing. In three behavioral experiments I find that participants are unable to ignore the duration of co-occurring sounds when giving visual duration judgments. Furthermore, prolonged sound duration goes along with improved detection sensitivity for visual stimuli and thus extends beyond duration judgments per se. I go on to test a cross-modal illusion in which the perceived number of flashes in a rapid series is affected by the number of co-occurring beeps (the sound-Induced flash illusion). Combining data from structural magnetic resonance imaging (MRI) and a behavioral experiment I find that individual proneness to this illusion is linked with less grey matter volume in early visual cortex. Finally, I test how co-occurring sounds affect the cortical representation of more natural visual stimuli. A functional MRI (fMRI) experiment investigates patterns of activation evoked by short video clips in visual areas V1-3. The trial-by-trial reliability of such patterns is reduced for videos accompanied by mismatching sounds. Turning from cross-modal effects to more intrinsic sources of contextual modulation I test how attention affects visual representations in V1-3. Using fMRI and population receptive field (pRF) mapping I find that high perceptual load at fixation renders spatial tuning for the surrounding visual field coarser and goes along with pRFs being radially repelled. In a final behavioral and fMRI experiment I find that the perception of face features is modulated by retinal stimulus location. Eye and mouth stimuli are recognized better, and evoke more discriminable patterns of activation in face sensitive patches of cortex, when they are presented at canonical locations. Taken together, these experiments underscore the importance of contextual modulation for vision, reveal some previously unknown such factors and point to possible neural mechanisms underlying them. Finally, they argue for an understanding of vision as a process using all available cues to arrive at optimal estimates for the causes of sensory events

Early visual contributions to reading

Reading requires integrating visual and linguistic processes, so it is perhaps surprising that models of visual word recognition focus almost entirely on language, to the exclusion of vision. Neurological models of reading assume that visual information proceeds serially from the retina through the early visual cortices, where a hierarchy of increasingly complex feature detectors transform the sensory-bound retinotopic code into progressively more abstract forms, eventually reaching reading-specialised populations that encode orthographic units. These orthographic detectors are the input pathway to the wider language system. This notion of a serial staged hierarchy culminating in abstract detectors, however, is likely overly simplistic. Evidence suggests that the occipitotemporal system is better understood as a highly recurrent network. Classical hierarchical accounts and interactive processing models make contrasting predictions about how early visual areas contribute to reading. To test these predictions, I retinotopically mapped occipital visual areas and then measured (fMRI) their neural response to different reading tasks. I found that reading strongly engaged areas V1-V3 bilaterally, both in the central (stimulated) regions and in regions coding the periphery, suggesting both bottom-up and top-down influences in early visual cortices. Within the central regions of V1-V3, activity was significantly stronger for low frequency than high frequency words, again suggesting that non-visual factors such as lexical frequency influence processing in the earliest visual areas. Subsequent analyses revealed that ventral (V4, VO-1, VO-2) and dorsal (V3a, V3b, V7) regions were both active during reading, with no evidence of any difference in the strength of activation between them. Lastly, I found that a seemingly incidental property of the experimental paradigm (stimulus presentation rate) dramatically affected V1-V3 activity. Together these results contradict the notion that the early visual stages of reading are tightly sensory-bound and require reading-specific neuronal representations. Rather, these findings suggest that reading is an interactive process, even in the earliest visual cortices

Multimodal Investigation of Brain Network Systems: From Brain Structure and Function to Connectivity and Neuromodulation

The field of cognitive neuroscience has benefited greatly from multimodal investigations of the human brain, which integrate various tools and neuroimaging data to understand brain functions and guide treatments for brain disorders. In this dissertation, we present a series of studies that illustrate the use of multimodal approaches to investigate brain structure and function, brain connectivity, and neuromodulation effects. Firstly, we propose a novel landmark-guided region-based spatial normalization technique to accurately quantify brain morphology, which can improve the sensitivity and specificity of functional imaging studies. Subsequently, we shift the investigation to the characteristics of functional brain activity due to visual stimulations. Our findings reveal that the task-evoked positive blood-oxygen-level dependent (BOLD) response is accompanied by sustained negative BOLD responses in the visual cortex. These negative BOLD responses are likely generated through subcortical neuromodulatory systems with distributed ascending projections to the cortex. To further explore the cortico-subcortical relationship, we conduct a multimodal investigation that involves simultaneous data acquisition of pupillometry, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). This investigation aims to examine the connectivity of brain circuits involved in the cognitive processes of salient stimuli. Using pupillary response as a surrogate measure of activity in the locus coeruleus-norepinephrine system, we find that the pupillary response is associated with the reorganization of functional brain networks during salience processing. In addition, we propose a cortico-subcortical integrated network reorganization model with potential implications for understanding attentional processing and network switching. Lastly, we employ a multimodal investigation that involves concurrent transcranial magnetic stimulation (TMS), EEG, and fMRI to explore network perturbations and measurements of the propagation effects. In a preliminary exploration on brain-state dependency of TMS-induced effects, we find that the propagation of left dorsolateral prefrontal cortex TMS to regions in the lateral frontoparietal network might depend on the brain-state, as indexed by the EEG prefrontal alpha phase. Overall, the studies in this dissertation contribute to the understanding of the structural and functional characteristics of brain network systems, and may inform future investigations that use multimodal methodological approaches, such as pupillometry, brain connectivity, and neuromodulation tools. The work presented in this dissertation has potential implications for the development of efficient and personalized treatments for major depressive disorder, attention deficit hyperactivity disorder, and Alzheimer's disease

Peripheral and Central Auditory Processing in People With Absolute Pitch

Absolute pitch (AP) is a rare ability that is defined by being able to name musical pitches without a reference standard. This ability has been of interest to researchers studying music cognition and the processing of pitch information because it is very rarely expressed and raises questions about developmental interactions between biological predispositions and musical training. This dissertation focuses mainly on the peripheral and central neural substrates and is divided into seven chapters. The first chapter reviews the anatomy, function, and frequency resolution of the auditory peripheral and central nervous system. It includes background information pertaining to the origins of AP and describes inconsistencies reported throughout a number of studies that characterize AP emergence. Chapter two details a series of peripheral experiments on twenty AP and thirty-three control subjects recruited for testing at two locations. The goal was to test whether frequency resolution differences could be resolved at the level of the cochlea within both groups as a potential correlate for the genesis of AP. Chapter three details two behavioural tests that were administered to assess the smallest frequency difference that AP musicians could resolve and to test how well they could detect melodic mistuning excerpts compared to non-AP musicians and controls without musical experience. Both AP musicians and non-AP musicians did significantly better in both tests compared to non-musicians. However, there were no differences between the AP and non-AP musician groups. Chapter four details a functional MRI study that measured frequency tuning in the cortex using a population receptive field (pRF) model that estimates preferred frequency bandwidth in each voxel. This method was also tested in auditory subcortical nuclei such as the inferior colliculus and medial geniculate nucleus. Chapter five reports the neuro-anatomical correlates of musicianship and AP using structural MRI. Here we investigated cortical thickness and volume differences among the three groups and found a number of regions differed significantly. Cortical thickness was significantly greater in the left Heschls gyrus (an area that acts as a central hub for auditory processing) in AP musicians compared to non-AP musicians and non-musicians. AP and non-AP musicians also exhibited increased cortical thickness and volume throughout their cortex and subcortex. In line with previous studies, AP musicians showed decreased cortical thickness and volume in frontal regions such as the pars opercularis part of the inferior frontal gyrus. Chapter six reports the neuro-anatomical correlates of musicianship and AP using diffusion tensor imaging (DTI) to measure connectivity and white matter structural integrity in regions associated with audition and language processing. Tracts connecting language processing regions were reduced in volume in AP musicians compared to their non-AP counterparts. Chapter seven includes the general discussion, which integrates the findings and results from the five experiments. Our findings indicate that the sharpness of frequency tuning did not differ in either peripheral or central auditory processing stages among AP and non-AP groups. This implies that AP possessors do not encode or represent auditory frequency any differently than other groups, from the periphery through auditory cortex; instead, the neural substrate of their abilities must lie elsewhere. The automatic and working memory independent categorization abilities in AP may reflect more refined efficiency in local but not global functional connectivity