MRgFUS thalamotomy lesion connectivity patterns linked to tremor control in Parkinson's disease

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an established thermoablative treatment for tremor. Although outcomes in Essential Tremor approach those of deep brain stimulation, efficacy in tremor-dominant Parkinsons disease (TDPD) is often less durable, with tremor relapse reported in 30-50% of cases. Previous associations with lesion size or age remain descriptive and do not explain why anatomically similar lesions yield divergent long-term outcomes. We retrospectively analyzed 20 patients with TDPD who underwent unilateral MRgFUS. Lesions were used as seeds for normative structural and functional connectivity analyses. Durable tremor control was associated with lesion showing stronger functional connectivity to primary motor (M1), primary somatosensory (S1), and supplementary motor areas, as well as inferior frontal and occipital cortices. In contrast, relapse was linked to greater connectivity with cerebellar motor and associative regions. Structurally, optimal lesions converged at the triangular interface of the nuclei ventralis intermedius, ventralis oralis, and ventro caudalis. Streamlines associated with better outcomes projected posteriorly towards S1, with M1 delineating an anterior functional boundary beyond which outcomes declined. Structural fingerprints emphasized posterior sensorimotor areas as critical therapeutic outputs. Findings define a connectivity-based substrate of durable tremor suppression and support the development of individualized, network-guided targeting strategies for MRgFUS in TDPD