Altered white matter connectivity associated with visual hallucinations following occipital stroke

Introduction: Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. Methods: We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age-matched controls. Results: Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. Conclusions: Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493–1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.York University Librarie

Altered White Matter Structure in Adults Following Early Monocular Enucleation

Visual deprivation from early monocular enucleation (the surgical removal of one eye) results in a number of long-term behavioural and morphological adaptations in the visual, auditory, and multisensory systems. This thesis aims to investigate how the loss of one eye early in life affects structural connectivity within the brain. A combination of diffusion tensor imaging and tractography was used to examine structural differences in 18 tracts throughout the brain of adult participants who had undergone early monocular enucleation compared to binocularly intact controls. We report significant structural changes to white matter in early monocular enucleation participants that extend beyond the primary visual pathway to include interhemispheric, auditory and multisensory tracts, as well as several long association fibres. Overall these results suggest that early monocular enucleation has long-term effects on white matter structure throughout the brain

Reduced structural connectivity between left auditory thalamus and the motion-sensitive planum temporale in developmental dyslexia

Developmental dyslexia is characterized by the inability to acquire typical reading and writing skills. Dyslexia has been frequently linked to cerebral cortex alterations; however recent evidence also points towards sensory thalamus dysfunctions: dyslexics showed reduced responses in the left auditory thalamus (medial geniculate body, MGB) during speech processing in contrast to neurotypical readers. In addition, in the visual modality, dyslexics have reduced structural connectivity between the left visual thalamus (lateral geniculate nucleus, LGN) and V5/MT, a cerebral cortex region involved in visual movement processing. Higher LGN-V5/MT connectivity in dyslexics was associated with the faster rapid naming of letters and numbers (RANln), a measure that is highly correlated with reading proficiency. We here tested two hypotheses that were directly derived from these previous findings. First, we tested the hypothesis that dyslexics have reduced structural connectivity between the left MGB and the auditory motion-sensitive part of the left planum temporale (mPT). Second, we hypothesized that the amount of left mPT-MGB connectivity correlates with dyslexics RANln scores. Using diffusion tensor imaging based probabilistic tracking we show that male adults with developmental dyslexia have reduced structural connectivity between the left MGB and the left mPT, confirming the first hypothesis. Stronger left mPT-MGB connectivity was not associated with faster RANnl scores in dyslexics, but in neurotypical readers. Our findings provide first evidence that reduced cortico-thalamic connectivity in the auditory modality is a feature of developmental dyslexia, and that it may also impact on reading related cognitive abilities in neurotypical readers

Visual brain areas in obsessive compulsive disorder : a diffusion tensor imaging approach

Dissertação de mestrado integrado em Psicologia (área de especialização em Psicologia Clínica)A Perturbação Obsessivo-Compulsiva (POC) é uma condição psiquiátrica pertencente ao espectro das perturbações de ansiedade, sendo caracterizada por obsessões e compulsões. Obsessões são definidas como pensamentos, imagens, ideias ou impulsos recorrentes cujo conteúdo causam um elevado grau de ansiedade no indivíduo, levando-o a executar ações especificas ou rituais mentais de modo a reduzir a ansiedade, i.e. compulsões, (DSM-IV-TR, APA, 2000). A POC é uma psicopatologia bastante debilitante com uma taxa de prevalência de 1 a 2,5% na população adulta, com diversas facetas no que diz respeito às suas características clínicas: comportamentais, emocionais e neurocognitivas. Com especial atenção, défices ao nível do processamento visual e um viés atencional são descritos como uma significante manifestação desta perturbação, desempenhando um papel importante na ineficiente apreensão de estímulos sociais, um importante característica desta perturbação. Em concordância, alterações cerebrais estruturais e funcionais têm sido associadas a este fenótipo. Deste modo, o principal objectivo é analisar a integridade da microestrutura de substância branca em pacientes com POC, através de técnicas de Imagiologia por Tensor de Difusão (do inglês Diffusion Tensor Imaging), usando uma metodologia baseada na segmentação e tractografia, de modo a estabelecer uma relação entre estes padrões de conexão cerebral e a sua sintomatologia clínica. Considerando os défices cognitivos e alterações cerebrais da POC, nomeadamente ao nível das áreas frontais (orbitofrontal e dorsolateral) e occipitais, pretendemos continuar investigações prévias da nossa equipa de investigação e examinar a integridade da substância branca dos feixes da circunvolução frontal inferior (CFI), lobo occipital e área V1, regiões cerebrais relacionadas com o processamento visuo-perceptivo, que hipotetizamos estarem alteradas na população com POC (Gonçalves et al., 2010). Recorrendo a uma inovadora técnica de imagiologia (DTI), foram avaliadas as medidas de integridade dos feixes de substância branca (FA, MD, AD e RD) das áreas da CFI, lobo occipital e V1 devido ao seu papel no processamento visual e perceptivo. Catorze pacientes com POC (idade média,M=32,64±11,41) e dez participantes no grupo controlo (idade média M=30,70±9,73), emparelhados em idade, sexo e lateralidade, participaram neste estudo. Os nosso resultados demonstraram diferenças entre pacientes e controlos em três medidas de DTI nas regiões occipitais e V1. Especificamente, o grupo com POC apresentou menor integridade dos feixes de substância branca nestas áreas cerebrais que estão estritamente relacionadas com o processamento visual. No entanto, não foram encontradas diferenças de grupo no que diz respeito às medidas de integridade da matéria branca no feixe da CFI. Os resultados sugerem que feixes de substância branca envolvidas no processamento precoce de estímulos visuais podem estar associadas às manifestações clínicas da POC, nomeadamente o viés de processamento de estímulos emocionais.Obsessive Compulsive Disorder (OCD) is a psychiatric disorder classified within the spectrum of anxiety disorders, being characterized by obsessions and compulsions. Obsessions are defined as thoughts, images, ideas or recurrent impulses which content causes an elevated degree of anxiety on the individual, impelling him to execute specific actions or mental rituals in order to reduce anxiety, i.e. compulsions, (DSM-IV-TR, APA, 2000). OCD is a very disabling psychopathology with a prevalence rate of 1 to 2,5% in the adult population, with several facets concerning its clinical features: behavioral, emotional and neurocognitive. Of special note, visual processing deficits and an attentional bias has been described as a significant manifestation of this disorder, playing an important role in their inefficient social stimuli aprehension, a important characteristic of this disorder. In agreement, structural and functional brain alterations in the occipital, parietal and other visual areas have been associated with this phenotype. Therefore, the main objective of the present study is to analyze white matter microstructure in OCD patients through the use of Diffusion Tensor Imaging (DTI) techniques, using a segmentation and tractography based approach, in order to establish a relation between connectivity patterns of these visual brain and OCD’ clinical symptomatology. Considering their neurocognitive phenotype and specific brain abnormalities in OCD, namely in frontal (orbitofrontal and dorsolateral) and occipital areas, we now aim to follow our team previous research and investigate the integrity of the Inferior Frontal Gyrus (IFG), occipital lobe and V1 area, as are related with visuo-perceptive processing, which we hypothesize to be abnormal in OCD population (Gonçalves et al., 2010). Using this innovative imaging technique (DTI) we evaluated white matter DTI-derived measures (FA, MD, AD and RD) of the IFG, occipital and V1 areas taking into account their role on visual processing and perception. Fourteen patients with OCD (Mean age=32,64 ± 11,41) and ten comparison controls (Mean age=30,70 ± 9,73), matched on age, sex and handedness, participated in this study. Our results reported group differences in three DTI indexes (MD, AD and RD) in occipital and V1. Specifically, OCD group displayed decreased integrity of these white matter tracts which are strictly related with visual processing. Nevertheless, we did not find group differences regarding the integrity of the IFG white matter tract. Results suggest that brain fiber tracts enrolled in early steges of visual processing may be associated with the clinical features of OCD, specifically the bias in processing for emotional stimuli

Using magnetic resonance imaging to assess visual deficits : a review

PURPOSE: Over the last two decades, magnetic resonance imaging (MRI) has been widely used in neuroscience research to assess both structure and function in the brain in health and disease. With regard to vision research, prior to the advent of MRI, researchers relied on animal physiology and human post-mortem work to assess the impact of eye disease on visual cortex and connecting structures. Using MRI, researchers can non-invasively examine the effects of eye disease on the whole visual pathway, including the lateral geniculate nucleus, striate and extrastriate cortex. This review aims to summarise research using MRI to investigate structural, chemical and functional effects of eye diseases, including: macular degeneration, retinitis pigmentosa, glaucoma, albinism, and amblyopia. RECENT FINDINGS: Structural MRI has demonstrated significant abnormalities within both grey and white matter densities across both visual and non-visual areas. Functional MRI studies have also provided extensive evidence of functional changes throughout the whole of the visual pathway following visual loss, particularly in amblyopia. MR spectroscopy techniques have also revealed several abnormalities in metabolite concentrations in both glaucoma and age-related macular degeneration. GABA-edited MR spectroscopy on the other hand has identified possible evidence of plasticity within visual cortex. SUMMARY: Collectively, using MRI to investigate the effects on the visual pathway following disease and dysfunction has revealed a rich pattern of results allowing for better characterisation of disease. In the future MRI will likely play an important role in assessing the impact of eye disease on the visual pathway and how it progresses over time

Altered white matter connectivity associated with visual hallucinations following occipital stroke

Introduction Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. Methods We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age‐matched controls. Results Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. Conclusions Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493–1500). Long‐term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations

Development of Low-Frequency Repetitive Transcranial Magnetic Stimulation as a Tool to Modulate Visual Disorders: Insights from Neuroimaging

Repetitive transcranial magnetic stimulation (rTMS) has become a popular neuromodulation technique, increasingly employed to manage several neurological and psychological conditions. Despite its popular use, the underlying mechanisms of rTMS remain largely unknown, particularly at the visual cortex. Moreover, the application of rTMS to modulate visual-related disorders is under-investigated. The goal of the present research was to address these issues. I employ a multitude of neuroimaging techniques to gain further insight into neural mechanisms underlying low-frequency (1 Hz) rTMS to the visual cortex. In addition, I begin to develop and refine clinical low-frequency rTMS protocols applicable to visual disorders as an alternative therapy where other treatment options are unsuccessful or where there are simply no existing therapies. One such visual disorder that can benefit from rTMS treatment is the perception of visual hallucinations that can occur following visual pathway damage in otherwise cognitively healthy individuals. In Chapters 23, I investigate the potential of multiday low-frequency rTMS to the visual cortex to alleviate continuous and disruptive visual hallucinations consequent to occipital injury. Combining rTMS with magnetic resonance imaging techniques reveals functional and structural cortical changes that lead to the perception of visual hallucinations; and rTMS successfully attenuates these anomalous visual perceptions. In Chapters 45, I compare the effects of alternative doses of low-frequency rTMS to the visual cortex on neurotransmitter levels and intrinsic functional connectivity to gain insight into rTMS mechanisms and establish the most effective protocol. Differential dose-dependent effects are observed on neurotransmitter levels and functional connectivity that suggest the choice of protocol critically depends on the neurophysiological target. Collectively, this work provides a basic framework for the use of low-frequency rTMS and neuroimaging in clinical application for visual disorders

How our brains are wired: Are the applications of diffusion imaging useful given the current limitations?

Diffusion imaging (DI) enables researchers to study white matter (WM) pathways in the human brain in-vivo by labelling water molecules and measuring their diffusion into different directions. Connectivity patterns are inferred assuming that water diffuses rather along than across fibre bundles. This paper introduces the concept of DI, addresses suitable applications and evaluates gains versus limitations. Common applications are (1) generating WM atlases, (2) mapping connectional models of functionally subdivided brain regions, (3) linking disorders to connectivity abnormalities, (4) verifying WM pathways from animal studies, (5) linking personality traits to particular connectivity patterns, (6) measuring structural changes resulting from experience or ageing and (7) presurgical planning. Despite limitations like the moderate spatial resolution, or – more fundamentally – the lack of a gold standard and the kissing/crossing problem, DI can be regarded as a useful tool if researchers choose methods carefully and consider the known limitations