A functional micro-electrode mapping of ventral thalamus in essential tremor

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.

Neuroimaging Detectable Differences between Parkinson's Disease Motor Subtypes: A Systematic Review

“…Activity in the BG and cerebellum has shown to be highly associated and structurally connected via the thalamus and pontine nucleus 117 . When targeted surgically with DBS, the Vim has shown to produce relief of tremor 21 and activity in the Vim that receives projections from the cerebellum, as well as from the GPi, has shown to synchronize with, mediate, and be directly related to tremor activity 118–121 . These finding are consistent with reports that the GP and putamen in TD patients have increased connectivity with the Vim–motor cortex–cerebellum circuit via the motor cortex 34 and further support results showing that a combination of STC and CTC circuitry might be behind the generation of tremors in PD 17 …”

Chronic embedded cortico-thalamic closed-loop deep brain stimulation for the treatment of essential tremor

“…Our data, along with other recent studies (45)(46)(47)(48)(49)(50) showed it is possible to directly use the VIM to detect movement and tremor features. However, the stimulation would adversely affect recording quality, especially when delivering stimulation to contacts adjacent to the recording site, rendering the detection of the termination of movement/tremor impossible.…”

Toward Electrophysiology-Based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders

“…Here, robust activity in the tremor frequency that can drive periodic muscle contractions [96][97][98][99][100] has been reported. The underlying multiunit activity was recently dissected in terms of the spatial distribution of efferent and afferent connections within the ventrolateral thalamic nuclei offering both spectral and spatial information for tremor-specific activity [100]. Cortical modulation of beta activity through voluntary movement was also demonstrated in ET patients [89,101], rendering ECoG a useful addition as a biomarker signal to differentiate voluntary and involuntary movements [102].…”

“…High-frequency stimulation of ventral intermediate nucleus (VIM) of the thalamus has shown great clinical success in the treatment of essential tremor [10][11][12][13]95]. Here, robust activity in the tremor frequency that can drive periodic muscle contractions [96][97][98][99][100] has been reported. The underlying multiunit activity was recently dissected in terms of the spatial distribution of efferent and afferent connections within the ventrolateral thalamic nuclei offering both spectral and spatial information for tremor-specific activity [100].…”