Striatal morphology correlates with frontostriatal electrophysiological motor processing in Huntington's disease: an IMAGE‐HD study

Abstract

BackgroundHuntington's disease (HD) causes progressive atrophy to the striatum, a critical node in frontostriatal circuitry. Maintenance of motor function is dependent on functional connectivity of these premotor, motor, and dorsolateral frontostriatal circuits, and structural integrity of the striatum itself. We aimed to investigate whether size and shape of the striatum as a measure of frontostriatal circuit structural integrity was correlated with functional frontostriatal electrophysiological neural premotor processing (contingent negative variation, CNV), to better understand motoric structure–function relationships in early HD.MethodsMagnetic resonance imaging (MRI) scans and electrophysiological (EEG) measures of premotor processing were obtained from a combined HD group (12 presymptomatic, 7 symptomatic). Manual segmentation of caudate and putamen was conducted with subsequent shape analysis. Separate correlational analyses (volume and shape) included covariates of age, gender, intracranial volume, and time between EEG and MRI.ResultsRight caudate volume correlated with early CNV latency over frontocentral regions and late CNV frontally, whereas right caudate shape correlated with early CNV latency centrally. Left caudate volume correlated with early CNV latency over centroparietal regions and late CNV frontally. Right and left putamen volumes correlated with early CNV latency frontally, and right and left putamen shape/volume correlated with parietal CNV slope.ConclusionsTiming (latency) and pattern (slope) of frontostriatal circuit‐mediated premotor functional activation across scalp regions were correlated with abnormalities in structural integrity of the key frontostriatal circuit component, the striatum (size and shape). This was accompanied by normal reaction times, suggesting it may be undetected in regular tasks due to preserved motor “performance.” Such differences in functional activation may reflect atrophy‐based frontostriatal circuitry despecialization and/or compensatory recruitment of additional brain regions.

Rate of torque development and striatal shape in individuals with prodromal Huntington's disease

“…Consistent with previous studies, significant differences in striatal shape metrics were observed between individuals with pro-HD and HC 26 , 27 . In particular, individuals with pro-HD displayed significant shape deflation in comparison with HC that was more evident for the right hemispheres of the putamen and caudate than for the left.…”

“…Together, these findings highlight the inherent variability in motor features across individuals with pro-HD, which has been well-documented in previous epidemiological studies and is presumed to relate to differences in striatal pathology, genetic burden, lifestyle and genetic modifiers, which could be the subject of future investigations. Consistent with previous studies, significant differences in striatal shape metrics were observed between individuals with pro-HD and HC 26,27 . In particular, individuals with pro-HD displayed significant shape deflation in comparison with HC that was more evident for the right hemispheres of the putamen and caudate than for the left.…”

Sleep in Huntington’s disease: a systematic review and meta-analysis of polysomongraphic findings

“…This could involve atrophy of brain areas that is increased with age in HD patients. Previous studies revealed that HD, which typically presents between 35 and 45 years of age [34], could cause progressive atrophy in the striatum [35]. Even in prodromal and early symptomatic HD, putamen atrophy rates of about 2.3% per year and 4.5% per year, and caudate atrophy rates of 1.1%-2.4% per year and 2.9%-4.9% per year, respectively, have been reported in comparisons to controls [36][37][38].…”

Time and relative dimensions in syndromology: Towards endophenotypes in neurology, psychiatry and in-between

“…Even in a clearly genetic disorder, great effort has been made into defining a clinical phenotype encompassing the prodromal period through to the development of neurological and psychiatric features. For example, there has been evidence that compensatory motoric electrophysiologic processes in HD are correlated with the structural integrity of neurocircuits serving these functions (Turner et al, 2016). The development of such multi-level pathophysiologic measures may lead to the better characterisation of endophenotypes, such as corticostriatal circuit dysfunction leading to cognitive, motoric and emotional manifestations.…”