Objective: To assess functional connectivity in the premanifest and manifest period of Huntington’s disease (HD) by using functional Magnetic Resonance Imaging (fMRI) at high-field (7 Tesla).

Background: HD is an autosomal dominant, progressive neurodegenerative disorder caused by an expanding CAG repeat in the Huntington’s gene. The natural history can be divided into premanifest (no detectable or subtle signs and symptoms of HD) and manifest (unequivocal motor signs) period. Progressive regional atrophy occurs early in the course of HD. Our previous study showed reduced cortico-striatal functional connectivity at rest in prodromal-HD subjects (Unschuld et al. Neurosci Letter 2012), but has not yet been replicated or demonstrated at 7 Tesla.

Methods: We assessed 10 subjects in the premanifest period of HD [age 43±9 years, CAG repeat 42±2, Unified Huntington’s disease Rating Scale (UHDRS) motor score 9 ±7, estimated years to symptom onset (YTO) 9 ±8 according to Langbehn et al. Clin Genet 2004], 10 subjects in the manifest period of HD [age 49 ±13 years CAG repeat 45+/-5, UHDRS motor score 30+/-20, YTO -7 ±7] and 10 matched healthy controls [age 47 ±12 years] by resting state fMRI scans at 7 Tesla. Because of the central role of the striatum in the pathogenesis of Huntington’s disease we assessed functional connectivity between the striatum and various cortical and sub-cortical regions, such as precentral, supplementary motor area, hippocampus, postcentral, angular, paracentral lobule, and thalamus. Two tailed t-test was applied for statistical analysis.

Results: Functional connectivity between striatum and supplementary motor area (Brodman areal 6 (3-5)) of the left hemisphere was impaired comparing HD subjects in the premanifest period with controls (P=0.03, F=5.3) and comparing manifest HD subjects with controls (P=0.01, F=7.8). P-values for all other comparisons were P>0.05, F<3.8.

Conclusions: These initial fMRI data indicate impaired functional connectivity between supplementary motor area and striatum in the premanifest period and the manifest period of HD, consistent with our previous data at 3 Tesla. With the enhanced sensitivity and spatial resolution at high-field, we will conduct advanced analysis to investigate functional connectivity between sub-striatal regions and the cortex in Huntington’s disease.

Presented for the first time.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/cortico-striatal-functional-connectivity-in-the-premanifest-and-manifest-period-of-huntingtons-disease-measured-with-high-field-functional-magnetic-resonance-imaging/