MR-guided Focused Ultrasound Thalamotomy Modulates Cerebellothalamo-cortical Tremor Network in Essential Tremor Patients

Li Jiang ^1* Dheeraj Gandhi ¹ Andrew Furman ¹ Howard M. Eisenberg ² Paul Fishman ³ Elias R. Melhem ¹ Rao P Gullapalli ¹ Jiachen Zhuo ^1*

• ¹ Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, United States
• ² Department of Neurosurgery, University of Maryland, Baltimore, United States
• ³ Department of Neurology, University of Maryland, Baltimore, United States

Objectives: To advance the mechanistic understanding of changes occurring to brain connectivity after successful MR-guided Focused Ultrasound ventral intermediate nucleus (VIM) thalamotomy for essential tremor (ET).Methods: This retrospective study included fifteen right-handed ET patients, who underwent successful unilateral VIM ablation and experienced improved hand tremor on their dominant hand. Resting-state fMRI scans were conducted both before and 1-year post-treatment for all participants. A seed-based whole brain resting-state functional connectivity (FC) analysis was performed, centering on tremor-related regions within the cerebello-thalamo-cortical (CTC) network, including the left and right ventral intermediate nucleus (VIM), primary motor cortex (M1H), and dentate nucleus (DN). The study examined both the changes in FC and their correlation with clinical outcomes evaluated using the Clinical Rating Scale for Tremor (CRST) at the 1-year post-treatment.Results: ET patients demonstrated significant tremor improvement at the treated hand, which persisted throughout the one-year study period. Compared with the baseline, FC of both left VIM and right VIM decreased in precentral gyrus and postcentral gyrus; FC of left M1 hand area increased in premotor cortex and supplemental motor area (SMA); and FC of left DN also increased in premotor cortex, SMA, M1, and anterior cingulate cortex (ACC). Association analysis between changes in left VIM functional connectivity and contralateral hand tremor scores revealed a significant negative correlation in the bilateral precentral gyrus, superior parietal lobule, precuneus, occipital cortex, and middle prefrontal cortex. Conversely, a significant positive correlation was observed in the frontal orbital cortex, right insular cortex, temporal pole, hippocampus, left lingual gyrus, right cerebellar lobules IV/V, left cerebellar lobule VI, and vermis IV/V.Our findings of altered functional connectivity within the cerebello-thalamocortical network, encompassing regions involved in motor, sensory, attention, visual, and visuospatial functions, and its association with hand tremor improvement suggest that targeting functional connectivity abnormalities may be a potential approach for alleviating tremor symptoms in ET patients.