Hierarchical Dynamic Causal Modeling of Resting-State fMRI Reveals Longitudinal Changes in Effective Connectivity in the Motor System after Thalamotomy for Essential Tremor

한글 요약

본태성 떨림 치료를 위해 시상의 특정 핵을 파괴하는 시상절제술이 운동 회로의 연결을 어떻게 장기적으로 바꾸는지를 방향성 있는 실효연결망(effective connectivity) 관점에서 규명한 연구입니다. 두개골을 열지 않는 MRI 유도 초음파 절제술을 받은 환자의 휴지기 fMRI를 수술 전부터 수술 후 여러 시점에 걸쳐 종단적으로 얻고, 스펙트럼 동적 인과 모델링(DCM)과 다층 경험 베이즈 분석으로 집단 수준의 시간적 변화를 추정했습니다. 수술 후 시상 복외측핵과 보조운동영역에서 반대쪽 소뇌 치상핵으로 향하는 연결이 선택적이고 일관되게 변했으며, 이 연결 변화는 임상 운동 증상 점수의 변화를 예측했습니다. 시상절제술이 시상-대뇌피질-소뇌 운동 고리를 통해 치상핵을 조절함으로써 효과를 낸다는 기전을 시사하며, 사람의 장기적 뇌 가소성을 비침습적으로 정량화하는 방법론으로서의 가치도 보여줍니다.

Thalamotomy at the ventralis intermedius nucleus for essential tremor is known to cause changes in motor circuitry, but how a focal lesion leads to progressive changes in connectivity is not clear. To understand the mechanisms by which thalamotomy exerts enduring effects on motor circuitry, a quantitative analysis of directed or effective connectivity among motor-related areas is required. We characterized changes in effective connectivity of the motor system following thalamotomy using (spectral) dynamic causal modeling (spDCM) for resting-state fMRI. To differentiate long-lasting treatment effects from transient effects, and to identify symptom-related changes in effective connectivity, we subject longitudinal resting-state fMRI data to spDCM, acquired 1 day prior to, and 1 day, 7 days, and 3 months after thalamotomy using a non-cranium-opening MRI-guided focused ultrasound ablation technique. For the group-level (between subject) analysis of longitudinal (between-session) effects, we introduce a multilevel parametric empirical Bayes (PEB) analysis for spDCM. We found remarkably selective and consistent changes in effective connectivity from the ventrolateral nuclei and the supplementary motor area to the contralateral dentate nucleus after thalamotomy, which may be mediated via a polysynaptic thalamic-cortical-cerebellar motor loop. Crucially, changes in effective connectivity predicted changes in clinical motor-symptom scores after thalamotomy. This study speaks to the efficacy of thalamotomy in regulating the dentate nucleus in the context of treating essential tremor. Furthermore, it illustrates the utility of PEB for group-level analysis of dynamic causal modeling in quantifying longitudinal changes in effective connectivity; i.e., measuring long-term plasticity in human subjects non-invasively.