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Immediate and Longitudinal Alterations of Functional Networks after Thalamotomy in Essential Tremor.

Authors: Jang C, Park HJ, Chang WS, Pae C, Chang JW

Thalamotomy at the ventralis intermedius nucleus has been an effective treatment method for essential tremor, but how the brain network changes immediately responding to this deliberate lesion and then reorganizes afterwards are not clear. Taking advantage of a non-cranium-opening MRI-guided focused ultrasound ablation technique, we investigated functional network changes due to a focal lesion. To classify the diverse time courses of those network changes with respect to symptom-related long-lasting treatment effects and symptom-unrelated transient effects, we applied graph-theoretic analyses to longitudinal resting-state functional magnetic resonance imaging data before and 1 day, 7 days, and 3 months after thalamotomy with essential tremor. We found reduced average connections among the motor-related areas, reduced connectivity between substantia nigra and external globus pallidum and reduced total connection in the thalamus after thalamotomy, which are all associated with clinical rating scales. The average connectivity among whole brain regions and inter-hemispheric network asymmetry show symptom-unrelated transient increases, indicating temporary reconfiguration of the whole brain network. In summary, thalamotomy regulates interactions over the motor network via symptom-related connectivity changes but accompanies transient, symptom-unrelated diaschisis in the global brain network. This study suggests the significance of longitudinal network analysis, combined with minimal-invasive treatment techniques, in understanding time-dependent diaschisis in the brain network due to a focal lesion.

Introduction

Purpose Thermoablation
Study Objective To characterize longitudinal functional brain network changes and distinguish symptom-related lasting effects from transient, symptom-unrelated effects following MRI-guided focused ultrasound thalamotomy for essential tremor.
Animal model / Human subject nonhuman primate, none, none, none
Disease model essential tremor
MRI or image guidance method MRI-guided focused ultrasound
Targeted brain region(s) Thalamus

Outcomes and Safety

Summary of Outcomes MRgFUS thalamotomy produced long-lasting reductions in motor-network connectivity (reduced thalamic node degree, average node strength and global efficiency) associated with improved tremor/posture scores, accompanied by transient, symptom-unrelated global network reconfiguration; no multiple focused-ultrasound parameter variants were tested.
Duration of biological effect 3 months
Safety-related matter The paper reports transient unintended effects after MRgFUS thalamotomy, including connectional/connectomal diaschisis, possible local brain edema, temporary neuronal 'knock-out' dysfunctions, and potential off-target lesioning of neighboring thalamic nuclei; these are discussed as transient and possibly recoverable. No specific clinical adverse events or long-term safety complications are reported in the study.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro
FUS Frequency not reported
FUS Intensity not reported
FUS Pressure not reported
FUS Mode not reported
Pulse duration not reported
Duration of a single FUS session not reported
Treatment frequency single

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