Stage‐Dependent Inhibitory Connectivity in Striatal‐Motor Circuit in Huntington's Disease

TL;DR

This study explores how brain connectivity changes in Huntington's disease across different stages, focusing on the striatal-motor circuit and its role in motor symptoms.

Contribution

The study identifies stage-dependent inhibitory connectivity changes in the striatal-motor circuit in Huntington's disease.

Findings

Abnormal spontaneous activity in the caudate nucleus and putamen correlates with their atrophy in Huntington's disease.

Increased inhibitory connectivity from the caudate nucleus to the motor cortex is observed in symptomatic HD patients.

Disrupted inhibitory connectivity in the striatal-motor circuit correlates with motor symptom severity in HD.

Abstract

Elucidating dysfunctional connectivity patterns among key brain regions in Huntington's disease (HD) underlying progression may have implications for developing treatment and therapeutic evaluation.

Explore the relationship between abnormal spontaneous resting‐state activity and atrophy in HD‐specific brain regions and clarify effective connectivity changes among them across different stages of HD.

Amplitude of low‐frequency fluctuation (ALFF) analysis was used to detect abnormal spontaneous neural activity; voxel‐based morphometry analysis was applied to assess atrophy; spectral dynamic causal model (DCM) was conducted to estimate regional effective connectivity between HD participants and healthy controls, as well as between preclinical mutation carriers and symptomatic patients.

Voxel‐wise whole‐brain ALFF analysis identified the bilateral caudate nucleus, putamen, and motor cortex as HD‐specific brain regions. ALFF changes in the caudate nucleus and putamen correlated with their respective volumetric atrophy, whereas ALFF changes in the motor cortex preceded its atrophy in the HD preclinical stage. Subsequently, DCM revealed increased inhibitory connectivity from the bilateral caudate nucleus to the motor cortex in HD participants compared to controls. Moreover, compared to preclinical mutation carriers, symptomatic patients showed decreased inhibitory connectivity from the right putamen to the bilateral caudate nucleus, with nonlinear relationships with motor scores.

Our results indicate that striatal atrophy and hyper‐inhibition of caudate‐motorial connectivity might contribute to the regional function alterations in HD. Furthermore, disruption of inhibitory connectivity in the striatal‐motor circuit may play an important role in the emergence of motor symptoms.

Figures