A functional micro-electrode mapping of ventral thalamus in Essential Tremor

Deep Brain Stimulation (DBS) 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 (VLp) has become a reliable DBS target for medically-refractory patients suffering from Essential Tremor (ET). But despite this, the contribution of the thalamus in ET, and even whether VLp is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the VLp that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during DBS surgery. Data were obtained from 10 severely affected ET-patients (12 hemispheres) undergoing DBS surgery. Our results demonstrate power and coherence maxima located in the inferior VLp 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 VLp. Taken together, these results provide important evidence for the role of the inferior VLp and its border region in ET pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high-resolution segregated DBS electrodes.