Structural and functional changes of the visual cortex in early Huntington's disease

Abstract

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder characterized by motor disturbances, psychiatric disturbances, and cognitive impairment. Visual cognitive deficits and atrophy of the posterior cerebral cortex are additionally present in early disease stages. This study aimed to assess the extent of structural and functional brain alterations of the visual cortex in HD gene carriers using different neuroimaging modalities. Structural and functional magnetic resonance imaging data were acquired from 18 healthy controls, 21 premanifest, and 20 manifest HD gene carriers. Voxel-based morphometry (VBM) analysis and cortical thickness measurements were performed to assess structural changes in the visual cortex. Brain function was measured by assessing neuronal connectivity changes in response to visual stimulation and at rest in visual resting-state networks. Multiple linear regression analyses were performed to examine the relationship between visual cognitive function and structural imaging measures. Compared to controls, pronounced atrophy and decreased neuronal function at rest were present in associative visual cortices in manifest HD. The primary visual cortex did not show group differences in cortical thickness and in vascular activity after visual stimulation. Thinning of the associative visual cortex was related to worse visual perceptual function. Premanifest HD gene carriers did not show any differences in brain structure or function compared to controls. This study improves the knowledge on posterior brain changes in HD, as our findings suggest that the primary visual cortex remains preserved, both structurally and functionally, while atrophy of associative visual cortices is present in early HD and linked to clinical visual deficits.

Structural brain correlates of dementia in Huntington’s disease

“…Our findings are in accordance with previous works showing that the development of cognitive deterioration in HD cannot be solely attributed to basal ganglia atrophy( Rosas et al, 2008 , Nopoulos et al, 2010 , Tabrizi et al, 2009 , Coppen et al, 2018 , Podoll et al, 1988 , Say et al, 2011 , Carmichael et al, 2019 , Harris et al, 2019 , Martinez-Horta et al, 2019 , Wolf et al, 2014 , Labuschagne et al, 2016 , Hinzen et al, 2018 , Chan et al, 2019 ). Structures of the basal ganglia, such as the caudate nucleus and putamen, but also the insular cortex, the PFC and the occipital and parietal cortex, strongly differentiated non-demented HD patients from healthy controls.…”

“…The involvement of cortical atrophy in HD, especially in parietal and occipital regions, is a well-known finding supported by several imaging studies( Rosas et al, 2008 , Rosas et al, 2005 , Kuwert et al, 1990 , Tabrizi et al, 2009 , Coppen et al, 2018 ). However, the functional translation of these cortical changes is partially understood.…”

“…Cross-sectional and longitudinal studies have illustrated that even in the premanifest stage of the disease, grey matter volume (GMV) reductions, cortical thinning (Cth), and reduced brain metabolism affect multiple extra-striatal regions. These regions comprise extensive territories of the parietal, temporal and occipital lobes that also contribute to the clinical expression of the disease( Rosas et al, 2008 , Rosas et al, 2005 , Nopoulos et al, 2010 , Tabrizi et al, 2009 , Coppen et al, 2018 , Rub et al, 2015 , Kuwert et al, 1990 ).…”

Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

“…In manifest HD the VIS showed abnormal functional connectivity changes in 4 out of 5 independent studies (Coppen et al, ; Dumas et al, ; Werner et al, ; Wolf, Sambataro, Vasic, Baldas, et al, ). Reduced connectivity within this network was functionally related to lower attention, visual scanning, and motor speed and with higher disease burden scores (Wolf, Sambataro, Vasic, Baldas, et al, ).…”

Patterns of CAG repeat instability in the central nervous system and periphery in Huntington’s disease and in spinocerebellar ataxia type 1

“…This difference parallels neuroanatomical observations in HD of only mild changes in retinal thickness by optical coherence tomography ( 52–54 ) and the lack of histopathological changes or aggregates in postmortem retina ( 55 ). In contrast, there is considerable neuronal cell loss in BA17 and atrophy of associative visual cortices ( 56 , 57 ) suggesting that visual impairment in HD is more likely due to central visual perception. In the periphery, as for the Boston cohort ( Fig.…”