Cerebellar Gray Matter Alterations in Huntington Disease: A Voxel-Based Morphometry Study

Abstract

Neuropathological and neuroimaging studies in Huntington disease (HD) have suggested a role for the cerebellum. Our goal was to perform a detailed evaluation of cerebellar morphology. We performed the Unified HD rating scale (UHDRS) and Montreal cognitive assessment (MOCA) in 26 HD patients and 26 healthy controls. We created a two-sample test to analyze cerebellar gray matter (GM) differences between groups and another to correlate GM alterations with UHDRS and MOCA, corrected for age, expanded cytosine-adenine-guanine repeats, and disease duration using the spatially unbiased atlas template (SUIT)-SPM-toolbox which preserves anatomical detailing. We found increased GM density in the anterior cerebellum compared to controls. Higher GM density in the postero-superior lobe correlated with mood symptoms. Worse motor function and better cognitive function correlated with GM changes in the posterior cerebellum (false discovery rate (FDR) correction p < 0.05 and k > 100 voxels). In this detailed study of the in vivo cerebellar morphology in HD, we observed GM changes in regions involved in sensorimotor integration, motor planning, and emotional processing, supporting cerebellar involvement in the neuropathological process of HD.

Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy

“…Limitations of the Talairach-Tournoux brain atlas are thus circumvented, enabling more accurate depiction than whole-brain methods offer. Previously conducted functional MRI studies relying on SUIT have successfully identified morphologic changes of cerebellar subregions in several neuropsychiatric diseases (Chen et al, 2018; Cocozza et al, 2017; de Azevedo et al, 2017; Piccinin et al, 2017). In addition, these studies showed that SUIT template preserves more anatomical detail of the cerebellum and allows for better localization of cerebellar findings than the commonly-used whole brain Voxel-based morphometry(VBM) MNI template.…”

Cerebellar atrophy and its contribution to cognition in frontotemporal dementias

“…Structural and functional abnormalities of the cerebellum are present in numerous developmental and acquired neurological conditions, such as developmental dyslexia, autism spectrum disorders, alcohol‐related brain damage, movement disorders (eg, Friedreich ataxia, Parkinson disease, Huntington disease), dementia (eg, Alzheimer disease [AD], dementia with Lewy bodies, frontotemporal dementia), and psychiatric disorders . The contribution of the cerebellum to motor coordination and motor planning is well known, but many studies have downplayed its involvement in other domains despite the mounting evidence over the past 30 years (eg, language, social cognition, interoception).…”

Montreal cognitive assessment for evaluating cognitive impairment in Huntington’s disease: a systematic review

“…The scale was used in six neuroimaging studies, 75 , 83 , 85 , 87 , 94 , 95 eight cognitive studies, 74 , 82 , 84 , 88 , 89 , 91 , 93 , 96 and three studies examining other clinical aspects of HD (eg, balance, dysphagia) 80 , 90 , 92 …”

“…Neuroimaging studies revealed that MoCA scores present significant correlation with N-acetylaspartate (NAA) and glutamate brain levels 75 and with gray matter density in the cerebellum 83 and subcortical structures 95 …”