Functional Connectivity of Primary Motor Cortex Is Dependent on Genetic Burden in Prodromal Huntington Disease

Koenig, Katherine A.; Lowe, Mark J.; Harrington, Deborah L.; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S.; Rao, Stephen M.

doi:10.1089/brain.2014.0271

Cited by 28 publications

(30 citation statements)

References 58 publications

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“…Several recent studies have addressed intrinsic neural function in preHD. Our findings are in accord with a study in a preHD group with a mean disease burden score of about 250 that showed preserved functional connectivity at rest21, with some evidence for M1/precuneus decoupling when employing a different analysis technique22. Significantly reduced synchronization in the sensory-motor network, particularly in the medial primary motor area (M1) posterior to the supplementary motor area, was detected by another study23.…”

Section: Discussionsupporting

confidence: 91%

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Gorges

Müller

Mayer

et al. 2017

Sci Rep

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Structural and functional changes attributable to the neurodegenerative process in Huntington’s disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.

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Section: Discussionsupporting

confidence: 91%

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Gorges

Müller

Mayer

et al. 2017

Sci Rep

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“…Indeed, the cohort of Müller et al () featured a lower impairment of motor abilities (as assessed with motor UHDRS scale). This assumption seems supported by studies in pre‐HD individuals, reporting reduced functional connectivity within the SMN (Koenig et al, ; Poudel et al, ; Unschuld et al, ). Lower connectivity in these individuals was associated with worse motor (Poudel et al, ) and cognitive abilities (Koenig et al, ).…”

Section: Resultsmentioning

confidence: 74%

“…This assumption seems supported by studies in pre‐HD individuals, reporting reduced functional connectivity within the SMN (Koenig et al, ; Poudel et al, ; Unschuld et al, ). Lower connectivity in these individuals was associated with worse motor (Poudel et al, ) and cognitive abilities (Koenig et al, ). Moreover, divergent connectivity changes in SMN were also observed between pre‐HD with lower and higher 5‐year probability of a clinical diagnosis (Koenig et al, ), which may suggest divergent connectivity abnormalities according to disease stage.…”

Section: Resultsmentioning

confidence: 74%

“…Lower connectivity in these individuals was associated with worse motor (Poudel et al, ) and cognitive abilities (Koenig et al, ). Moreover, divergent connectivity changes in SMN were also observed between pre‐HD with lower and higher 5‐year probability of a clinical diagnosis (Koenig et al, ), which may suggest divergent connectivity abnormalities according to disease stage. Therefore, increased connectivity within the “motor corticocerebellar system” may characterize the manifest HD stage and linked with characteristic motor symptoms, while in the prodromal stage reduced “motor system” connectivity is observed.…”

Section: Resultsmentioning

confidence: 99%

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Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

Pini

Jacquemot

Cagnin

et al. 2019

Human Brain Mapping

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Resting‐state functional magnetic resonance imaging (rs‐fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic literature review was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs‐fMRI. We included studies investigating connectivity in presymptomatic (pre‐HD) and manifest HD gene carriers compared to healthy controls, implementing seed‐based connectivity, independent component analysis, regional property, and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre‐HD, showing disease stage‐dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior–posterior alterations, possibly reflecting compensatory mechanisms. The involvement of these networks in pre‐HD is still unclear. In conclusion, aberrant connectivity of the sensory‐motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory‐motor and executive networks exhibit hyper‐ and hypo‐connectivity patterns following different spatiotemporal trajectories. These findings could potentially help to implement future huntingtin‐lowering interventions.

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“…, ; Koenig et al. ). Electroencephalography (EEG) shows promise in identifying subtle changes in integrity of motor processing, and may offer new insights into the mismatch between neural atrophy and successful motor performance (Turner et al.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Functional Connectivity of Primary Motor Cortex Is Dependent on Genetic Burden in Prodromal Huntington Disease

Cited by 28 publications

References 58 publications

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

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

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