Distinct cerebellar regions related to motor and cognitive performance in SCA6 patients

Abstract

Objective To demonstrate a correlation between anatomic regional changes in Spinocerebellar Ataxia type 6 (SCA6) patients and measures of cognitive performance on neuropsychological tests. Methods Neurocognitive testing was conducted on 24 SCA6 and 28 control subjects. For each cognitive test, SCA6 patients were compared against the controls using Student’s t-test. For the cerebellar patients, using voxel based morphometry, correlations between cerebellar gray matter volume at each voxel and performance on the neuropsychological exams were calculated using the Pearson correlation coefficient implemented in SPM8. Results Compared to controls, SCA6 patients exhibited significantly impaired performance on the following cognitive tests: Rey-Auditory Verbal Learning Test Trial V, Controlled Oral Word Association phonemic test and semantic-verb test, Rey-Osterrieth Complex Figure copy test as well as immediate and delayed visuo-spatial memory recall test, Trail Making Test (TMT) Part A and Part B, Stroop Color Task completion time, Stroop Color-Word Task score, and Grooved Pegboard Test (GPT) Dominant and Non-Dominant Hand time. Correlations of gray matter density with cognitive test performance were determined for all SCA6 subjects. Using a p-value threshold of 0.001 and family-wise small volume error correction, significant correlations were found for GPT Non-Dominant, GPT Dominant, TMT Part A, and TMT Part B. Conclusion Different regional patterns of cerebellar involvement were found for the motoric GPT task and the executive version of the TMT. The results for the GPT strongly indicated that the integrity of medial superior hemispheric regions was associated with motor task performance, whereas executive cognitive function was localized in distinctly different inferior regions. This is the first VBM study to differentiate cognitive and motor contributions of the cerebellum.

Action perception recruits the cerebellum and is impaired in spinocerebellar ataxia patients

“…Future studies could include fMRI of SCA6 patients to explore where in the cerebellum degeneration alters task-related activity, and whether this includes regions associated with gaze-control. A previous VBM study points to a loss of gray matter in the hemispheres of lobule VI as the primary cause of upper limb ataxia triggered by SCA6 (Rentiya et al, 2017), which is in close vicinity to and partly overlaps with regions in which we find cerebellar activations to action observation, but is lateral relative to the sections of lobule VI mostly associated with eye movements ( Supplementary Fig. 3).…”

“…SCA6 is a rare late-onset neurodegenerative disorder characterized by ataxia and associated with a loss of Purkinje cells in the cerebellum. A Voxel-based morphology study points to loss of gray matter in the hemispheres of lobule VI (Rentiya et al, 2017) as being the primary cause of the upper limb ataxia -adjacent to regions in which we find cerebellar activations to action observation in part I. Task performance was compared with that of 31 age matched controls.…”

Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia

“…Future studies could include functional MRI of SCA6 patients to explore where in the cerebellum degeneration alters task-related activity, and whether this includes regions associated with gaze-control. A previous voxel-based morphometry study points to a loss of grey matter in the hemispheres of lobule VI as the primary cause of upper limb ataxia triggered by SCA6 ( Rentiya et al , 2017 ), which is in close vicinity to and partly overlaps with regions in which we found cerebellar activations to action observation, but is lateral relative to the sections of lobule VI mostly associated with eye movements ( Supplementary Fig. 5 ).…”

“…SCA6 is a rare late-onset neurodegenerative disorder characterized by ataxia and associated with a loss of Purkinje cells in the cerebellum ( Du et al , 2013 ). A voxel-based morphology study points to loss of grey matter in the hemispheres of lobule VI ( Rentiya et al , 2017 ) as being the primary cause of the upper limb ataxia—adjacent to regions in which we found cerebellar activations to action observation in part one of our study. Task performance was compared with that of 31 age-matched control subjects.…”

Brain-predicted age difference score is related to specific cognitive functions: A multi-site replication analysis

“…Tentative neurobiological support can be found for this correlation in the overlap in correlations between TMT B performance and GM volume in regions containing voxels which contribute heavily to brainPAD in our model. TMT B performance is negatively correlated with medial temporal lobe atrophy (Oosterman et al, 2010) and is positively related with GM density within the cerebellum in patients with spinocerebellar ataxia (Rentiya, Khan, Ergun, Ying, & Desmond, 2017). This evidence could suggest that brainPAD may be a potential objective measure of cognitive decline as it is not subject to the same factors which bias trail-making performance, including to practice effects (Bartels, Wegrzyn, Wiedl, Ackermann, & Ehrenreich, 2010), rater effects (Feeney et al, 2016) and participant literacy (Vaucher et al, 2014).…”