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

Abstract

Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal (6 months) within-subject crossover protocol (DBS OFF, OL-DBS, and CL-DBS). Most patients with ET experience involuntary limb tremor during goal-directed movements, but not during rest. Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulation amplitude based on patient-specific motor behavior, suppressing the pathological tremor on-demand based on a cortical electrode detecting upper limb motor activity. Here, we demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal and distal posture, water pouring, and writing) while having a consistent reduction in energy delivery. The proposed paradigm is an important step toward a behaviorally modulated fully embedded DBS system, capable of delivering stimulation only when needed, and potentially mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device replacement.

The sensitivity of ECG contamination to surgical implantation site in adaptive neurostimulation

“…Moreover, given the proximity of the ECG artifact to the LFP noise floor, higher amplitude signals, e.g. recorded with electrocorticography, will not suffer from ECG and may be viable for certain aDBS applications [6,[12][13][14]. Finally, given the brevity of the high amplitude QRS component, post-hoc processing can restore a significant portion (~80%) underlying neural activity in many contaminated signals, but even if this proves possible in real-time it will involve additional power consumption.…”

Subthalamic-Cortical Network Reorganization during Parkinson’s Tremor

“…These results overall argue for a combined subcortical-cortical stimulation/recording paradigm not unlike corticalthalamic closed-loop DBS for ET (Opri et al, 2020). By combining recordings from the STN and sensorimotor cortex, an algorithm could infer whether tremor was about to emerge (STN and MC θ) or was already present (SC θ).…”

Advances in Carbon-Based Microfiber Electrodes for Neural Interfacing

“…This is a significant material sciences challenge as the electrode materials need to possess a wide range of electrochemical properties if they are to be used for both recording and stimulation. Examples of clinical applications that may benefit from the use of closed-loop system include epilepsy prediction and treatment via electrical stimulation of spinal cord (Berenyi et al, 2012;Pais-Vieira et al, 2016), deep brain stimulation for Parkinson's diseases treatment (Fleming et al, 2020) and tremor suppression (Opri et al, 2020). In these applications, the use of closed-loop system has been shown with similar or even better clinical efficacy compared to the use of open-loop system, while having a consistent reduction in energy requirement (Fleming et al, 2020;Opri et al, 2020).…”