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

• Published in: Brain and behavior 2016-12, Vol.6 (12), p.e00511-n/a
• Main Authors: Turner, Lauren M., Jakabek, David, Wilkes, Fiona A., Croft, Rodney J., Churchyard, Andrew, Walterfang, Mark, Velakoulis, Dennis, Looi, Jeffrey C. L., Georgiou‐Karistianis, Nellie, Apthorp, Deborah
• Format: Article
• Language: English
• Subjects: Adult; Atrophy; Caudate Nucleus - diagnostic imaging; Caudate Nucleus - pathology; Caudate Nucleus - physiopathology; Compensation; Electroencephalography; Electroencephalography - methods; Female; Humans; Huntington Disease - diagnostic imaging; Huntington Disease - pathology; Huntington Disease - physiopathology; Huntington's disease; Huntingtons disease; Magnetic Resonance Imaging - methods; Male; Middle Aged; Morphology; motor; motor response potentials; NMR; Nuclear magnetic resonance; Original Research; Psychomotor Performance - physiology; Putamen - diagnostic imaging; Putamen - pathology; Putamen - physiopathology; Software; striatum; structural; Structure-Activity Relationship
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.511

Background Huntington'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. Methods Magnetic 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. Results Right 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. Conclusions Timing (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. Research on Huntington's disease (HD) suggests that presymptomatic individuals show no functional motor abnormalities despite significant and well‐established structural degeneration; however, our previous paper (Turner et al., PLoS One, 2015) identified aberrant premotor activation, which we suggest implicated frontostriatal network impairment. Here, we expand on our first study to demonstrate correlations between premo