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MR-guided focused ultrasound thalamotomy modulates cerebello-thalamo-cortical tremor network in essential tremor patients.

Authors: Jiang L, Gandhi D, Furman A, Eisenberg HM, Fishman P, Melhem ER, Gullapalli RP, Zhuo J

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). 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. ET patients demonstrated significant tremor improvement at the treated hand, which persisted throughout the 1-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-thalamo-cortical 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.

Introduction

Purpose thermal ablation
Study Objective Investigate long-term (1-year) changes in resting-state functional connectivity within the cerebello-thalamo-cortical tremor network after unilateral MRgFUS VIM thalamotomy in essential tremor patients
Animal model / Human subject human (essential tremor patients)
Disease model essential tremor
MRI or image guidance method Yes (MRI)
Targeted brain region(s) Thalamus
Target coordinates approximately 1/4 distance from PC to AC, 14-15 mm from midline in AC-PC plane

Outcomes and Safety

Summary of Outcomes Fifteen ET patients underwent unilateral VIM MRgFUS thalamotomy. Hand tremor (treated side) significantly improved from baseline (11.33±3.50) to 1-year (5.08±2.88) (p<0.001). Functional connectivity analysis: left VIM (treated) showed decreased FC with sensorimotor cortex; left M1H and left dentate nucleus showed increased FC with premotor/SMA/ACC. Changes in left VIM FC correlated with tremor improvement in motor, sensory, attention, visual, and visuospatial regions.
Duration of biological effect 1 year (follow-up period)

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro System (InSightec), MR-guided focused ultrasound, 3T MRI scanner
Treatment frequency single session (unilateral thalamotomy, multiple sonications within session)

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