Dynamic functional changes upon thalamotomy in essential tremor depend on baseline brain morphometry

Abstract

Abstract Patients with drug-resistant essential tremor (ET) may undergo Gamma Knife stereotactic radiosurgical thalamotomy (SRS-T), where the ventro-intermediate nucleus of the thalamus (Vim) is lesioned by focused beams of gamma radiations to induce clinical improvement. Here, we studied SRS-T impacts on left Vim dynamic functional connectivity (dFC, n = 23 ET patients scanned before and 1 year after intervention), and on surface-based morphometric brain features (n = 34 patients, including those from dFC analysis). In matched healthy controls (HCs), three dFC states were extracted from resting-state functional MRI data. In ET patients, state 1 spatial stability increased upon SRS-T (p = 0.0041). Lower pre-intervention spatial variability in state 2 expression, and more frequent expression of state 3 over state 1, correlated with greater clinical recovery (p = 0.015 and p = 0.008, respectively). ET morphometric profiles showed significantly lower similarity to HCs in 13 regions upon SRS-T (p ≤ 0.02), and a joint analysis revealed that before thalamotomy, morphometric similarity and states 2/3 mean spatial similarity to HCs were anticorrelated, a relationship that disappeared upon SRS-T (p < 0.001). Our results show that left Vim functional dynamics directly relates to upper limb tremor lowering upon intervention, while morphometry instead has a supporting role in reshaping such dynamics.