Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Essential tremor is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus of the thalamus and/or the posterior subthalamic area has been shown to provide significant tremor suppression in patients with essential tremor, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the CNS, including cerebellar, motor cortex or peripheral nerves, have also been developed for treating essential tremor, but the clinical outcomes remain inconsistent. Existing studies suggest that pathology in essential tremor might emerge from multiple cortical and subcortical areas, but its exact mechanisms remain unclear.
By simultaneously capturing neural activities from motor cortices and thalami and recording hand tremor signals via accelerometers in 15 human subjects who had undergone lead implantations for DBS, we systematically characterized the efferent and afferent cortico-thalamic tremor networks. Through the comparisons of these network characteristics and tremor amplitude between DBS off and on conditions, we also investigated the associations between different tremor network characteristics and the magnitude of the DBS effect.
Our findings implicate the thalamus, specifically the contralateral hemisphere, as the primary generator of tremor in essential tremor, also with a significant contribution of the ipsilateral hemisphere. Although there is no direct correlation between the cortico-tremor connectivity and tremor power or reduced tremor by DBS, the strength of connectivity from the motor cortex to the thalamus and vice versa at tremor frequency predicts baseline tremor power and effect of DBS. Interestingly, there is no correlation between these two connectivity pathways themselves, suggesting that, independent of the subcortical pathway, the motor cortex appears to play a relatively distinct role, possibly mediated through an afferent/feedback loop in the propagation of tremor. DBS has a greater clinical effect in those with stronger cortico-thalamo-tremor connectivity involving the contralateral thalamus, which is also associated with bigger and more stable tremor measured with an accelerometer. Interestingly, stronger cross-hemisphere coupling between left and right thalami is associated with more unstable tremor.
This study provides important insights for a better understanding of the cortico-thalamic tremor-generating network and its implication for the development of patient-specific therapeutic approaches for essential tremor.
By simultaneously capturing neural activities from motor cortices and thalami and recording hand tremor signals via accelerometers in 15 human subjects who had undergone lead implantations for DBS, we systematically characterized the efferent and afferent cortico-thalamic tremor networks. Through the comparisons of these network characteristics and tremor amplitude between DBS off and on conditions, we also investigated the associations between different tremor network characteristics and the magnitude of the DBS effect.
Our findings implicate the thalamus, specifically the contralateral hemisphere, as the primary generator of tremor in essential tremor, also with a significant contribution of the ipsilateral hemisphere. Although there is no direct correlation between the cortico-tremor connectivity and tremor power or reduced tremor by DBS, the strength of connectivity from the motor cortex to the thalamus and vice versa at tremor frequency predicts baseline tremor power and effect of DBS. Interestingly, there is no correlation between these two connectivity pathways themselves, suggesting that, independent of the subcortical pathway, the motor cortex appears to play a relatively distinct role, possibly mediated through an afferent/feedback loop in the propagation of tremor. DBS has a greater clinical effect in those with stronger cortico-thalamo-tremor connectivity involving the contralateral thalamus, which is also associated with bigger and more stable tremor measured with an accelerometer. Interestingly, stronger cross-hemisphere coupling between left and right thalami is associated with more unstable tremor.
This study provides important insights for a better understanding of the cortico-thalamic tremor-generating network and its implication for the development of patient-specific therapeutic approaches for essential tremor.
Date Issued
2025-06-01
Date Acceptance
2024-11-01
Citation
Brain, 2025, 148 (6), pp.2093-2107
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Start Page
2093
End Page
2107
Journal / Book Title
Brain
Volume
148
Issue
6
Copyright Statement
© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which per mits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39592428
7909131
Grant Number
MR/X023141/1
Subjects
deep brain stimulation
directed connectivity
efferent and afferent
essential tremor
local field potential
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Neurology & Neurosurgery
Publication Status
Published
Coverage Spatial
England
Article Number
awae387
Date Publish Online
2024-11-27