Jing Yinghua, Dogan Imis, Overbeck Rena Theda, Reetz Kathrin, Romanzetti Sandro
Department of Neurology, RWTH Aachen University, Aachen, Germany.
JARA-Brain Institute Molecular Neuroscience and Neuroimaging (INM-11), Research Centre Jülich and RWTH Aachen University, Aachen, Germany.
Ann Clin Transl Neurol. 2025 Aug;12(8):1628-1637. doi: 10.1002/acn3.70104. Epub 2025 Jun 12.
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.
阐明亨廷顿舞蹈症（HD）进展过程中关键脑区之间功能失调的连接模式可能对开发治疗方法和疗效评估具有重要意义。
探讨HD特异性脑区异常自发静息态活动与萎缩之间的关系，并阐明HD不同阶段这些脑区之间有效连接性的变化。
采用低频振幅（ALFF）分析检测异常自发神经活动；运用基于体素的形态学分析评估萎缩情况；采用频谱动态因果模型（DCM）估计HD患者与健康对照之间以及临床前突变携带者与有症状患者之间的区域有效连接性。
基于体素的全脑ALFF分析确定双侧尾状核、壳核和运动皮层为HD特异性脑区。尾状核和壳核的ALFF变化与其各自的体积萎缩相关，而运动皮层的ALFF变化在HD临床前阶段先于其萎缩出现。随后，DCM显示与对照组相比，HD患者从双侧尾状核到运动皮层的抑制性连接增加。此外，与临床前突变携带者相比，有症状患者从右侧壳核到双侧尾状核的抑制性连接减少，且与运动评分呈非线性关系。
我们的结果表明，纹状体萎缩和尾状核-运动连接的过度抑制可能导致HD中的区域功能改变。此外，纹状体-运动回路中抑制性连接的破坏可能在运动症状的出现中起重要作用。
