Glaucoom wordt traditioneel als een oogziekte gezien, maar verschillende MRI-onderzoeken tonen veranderingen in de rest van het visuele systeem in de hersenen aan die wijzen op schade. Dit zou verklaard kunnen worden doordat de hersenen minder visuele input krijgen, maar zou ook kunnen betekenen dat glaucoom een hersencomponent heeft. Deze openstaande vraag heb ik onderzocht door het analyseren van hersenscans van patienten met glaucoom (zowel uit Europa als Japan), mensen met eenzijdige blindheid en gezonde controles. Ik vond voor glaucoom — en niet eenzijdige blindheid — aanwijzingen voor neurodegeneratie in het visuele systeem. Dit suggereert dat enkel verminderde visuele input deze veranderingen niet kan verklaren. Daarnaast onderzocht ik hersenstructuren buiten het visuele systeem. Ik vond dat zowel glaucoom als eenzijdige blindheid zijn geassocieerd met witte stof veranderingen in visueel-gerelateerde en niet-visuele hersenstructuren. Echter, die in glaucoom zijn meer uitgebreid (bijvoorbeeld meer aangedane hersenstructuren). Naar mijn mening wijzen dit op de bijdrage van een onafhankelijke hersencomponent in glaucoom. Dit proefschrift draagt daarmee bij aan het idee dat in de toekomst neuroprotectieve medicatie kan worden voorgeschreven om neurodegeneratie van het visuele systeem en andere hersenstructuren te voorkomen, in aanvulling op de standaardbehandeling die gericht is op het oog. Bovendien stelt de betrokkenheid van de hersenen voor dat neuroimaging - mettertijd - nodig is voor de klinische evaluatie van de voortgang en behandeling van de ziekte. Mijn aanbeveling voor toekomstig onderzoek is het ontwikkelen van MRI-gebaseerde instrumenten die in staat zijn om ziekteprogressie in de hersenen te evalueren en monitoren op een individueel niveau.
Abstract The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test–retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.
Neural processing of speech production has been traditionally attributed to the left hemisphere. However, it remains unclear if there are structural bases for speech functional lateralization and if these may be partially explained by sexual dimorphism of cortical morphology. We used a combination of high-resolution MRI and speech-production functional MRI to examine cortical thickness of brain regions involved in speech control in healthy males and females. We identified greater cortical thickness of the left Heschl's gyrus in females compared to males. Additionally, rightward asymmetry of the supramarginal gyrus and leftward asymmetry of the precentral gyrus were found within both male and female groups. Sexual dimorphism of the Heschl's gyrus may underlie known differences in auditory processing for speech production between males and females, whereas findings of asymmetries within cortical areas involved in speech motor execution and planning may contribute to the hemispheric localization of functional activity and connectivity of these regions within the speech production network. Our findings highlight the importance of consideration of sex as a biological variable in studies on neural correlates of speech control.
The emerging view of dystonia is that of a large-scale functional network disorder, in which the communication is disrupted between sensorimotor cortical areas, basal ganglia, thalamus, and cerebellum. The structural underpinnings of functional alterations in dystonia are, however, poorly understood. Notably, it is unclear whether structural changes form a larger-scale dystonic network or rather remain focal to isolated brain regions, merely underlying their functional abnormalities. Using diffusion-weighted imaging and graph theoretical analysis, we examined inter-regional white matter connectivity of the whole-brain structural network in two different forms of task-specific focal dystonia, writer's cramp and laryngeal dystonia, compared to healthy individuals. We show that, in addition to profoundly altered functional network in focal dystonia, its structural connectome is characterized by large-scale aberrations due to abnormal transfer of prefrontal and parietal nodes between neural communities and the reorganization of normal hub architecture, commonly involving the insula and superior frontal gyrus in patients compared to controls. Other prominent common changes involved the basal ganglia, parietal and cingulate cortical regions, whereas premotor and occipital abnormalities distinctly characterized the two forms of dystonia. We propose a revised pathophysiological model of focal dystonia as a disorder of both functional and structural connectomes, where dystonia form-specific abnormalities underlie the divergent mechanisms in the development of distinct clinical symptomatology. These findings may guide the development of novel therapeutic strategies directed at targeted neuromodulation of pathophysiological brain regions for the restoration of their structural and functional connectivity.
Abstract Purpose Glaucoma is the most common age‐related neurodegenerative eye disease in western society. It is an insidious disease that, when untreated or detected too late, leads inevitably to blindness. An outstanding issue is whether glaucoma should be considered exclusively an eye disease or also a brain disease. To further examine it, we used Diffusion Tensor Imaging ( DTI ) to study white matter integrity in a Japanese glaucoma population. This population has a very high incidence of normal‐pressure glaucoma, in which optic nerve damage occurs in the absence of the elevated eye pressure that characterises the more common form of glaucoma. Methods We performed DTI in 30 participants with normal‐pressure glaucoma and 21 age‐matched healthy controls. We used voxel‐wise tract‐based spatial statistics to compare fractional anisotropy and mean diffusivity of the white matter of the brain between patients and control group. Whole‐brain and region of interest‐based analyses served to find associations between diffusion indices and clinical measures of glaucomatous damage. Results Fractional Anisotropy was significantly lower in glaucoma patients in a cluster in the right occipital lobe ( p < 0.05; family‐wise error‐corrected) comprising fibres of both the optic radiation and the forceps major. Additional analysis confirmed bilateral involvement of the optic radiations and forceps major and additionally revealed damage to the corpus callosum and parietal lobe ( p < 0.09; family‐wise error‐corrected). The region of interest‐based analysis revealed a positive association between Fractional Anisotropy of the optic radiation and optic nerve damage. Conclusions In this specific population, glaucoma is associated with lower Fractional Anisotropy in the optic radiations, forceps major and corpus callosum. We interpret these reductions as evidence for white matter degeneration in these loci. In particular, the degeneration of the corpus callosum suggests the presence of neurodegeneration of the brain beyond what can be explained on the basis of propagated retinal and pre‐geniculate damage. We discuss how this finding links to the emerging view that a brain component that is independent from the eye damage plays a role in the aetiology of glaucoma.
Background: Children with auditory processing disorders (APD) seem to have difficulties in auditory functioning, and with cognitive, language and reading tasks. However, it is not clear whether the behavioural characteristic of children with APD are distinctive from the behavioural characteristics of children with another developmental disorder, like specific language impairment (SLI), dyslexia, attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD). Aim: The aim of this study was to determine which characteristics overlap between children with APD versus SLI, dyslexia, ADHD, or ASD.
Abstract The degree to which glaucoma has effects beyond the eye –in the brain– is unclear. We investigated white matter microstructure (WMM) alterations in 37 tracts of patients with glaucoma, monocular blindness and controls. We used reproducible methods and the advanced cloud computing platform brainlife.io . White matter tracts were subdivided into seven categories ranging from primarily involved in vision (the visual white matter) to primarily involved in cognition and motor control. WMM in both glaucoma and monocular blind subjects was lower than controls in the visual white matter, suggesting neurodegenerative mechanisms due to reduced sensory inputs. In glaucoma participants WMM differences from controls decreased outside the visual white matter. A test-retest validation approach was used to validate these results. The pattern of results was different in monocular blind participants, where WMM properties increased outside the visual white matter as compared to controls. The pattern of results suggests that whereas in the blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the brain plasticity effects that in other patient groups follow visual loss.
