Abstract
Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes.
Highlights
Essential tremor refractory to medical treatment is a frequent indication for deep brain stimulation (DBS) lead placement
We have identified tremor-related power and thalamomuscular coherence increases relative to baseline that were spatially focal about ventral thalamus
We found that predominantly efferent pockets outnumbered afferent ones, but that their spatial topography was indistinguishable
Summary
Essential tremor refractory to medical treatment is a frequent indication for deep brain stimulation (DBS) lead placement. DBS surgery offers the opportunity to record brain activity that may provide important insight into the pathomechanisms of essential tremor. To appreciate the contribution and organization of thalamic neurons to tremor, a more detailed view is required. This is especially important when we consider that there is ongoing debate over the efficiency of stimulating the thalamus, versus stimulation applied immediately below its VLp division (King et al, 2017). In view of the possible segregated efferent drive and resonant reafference, a more detailed view on the characteristics of tremor in both the thalamus and the areas immediately ventral are important in the development of tailored therapies for essential tremor. In-so-doing we tested the over-arching hypothesis that tremor-related activity in focal clusters of thalamic neurons organizes and helps drive tremulous arm movements
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