Closed-loop low-frequency DBS restores thalamocortical relay fidelity in a computational model of the motor loop.

Abstract

Closed-loop modulation of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is investigated to automatically adjust the stimulation to the patients' conditions, optimize the clinical outcomes, and reduce the energy requirements. This study proposes a closed-loop control system for real-time adaptation of the STN-DBS amplitude based on the neural activity in the motor thalamus. Population-averaged post-stimulus time histograms are used to measure the average effects of STN-DBS on the thalamocortical neurons and a L2-norm minimization problem is solved to design the control algorithm, while the frequency of stimulation is kept constant. Applied on a large-scale, biophysically-based, anatomically-compliant model of the cortico-basal ganglia-thalamo-cortical motor loop under PD conditions, our adaptive DBS significantly (P-value P<;0.05) improved the relay fidelity of the thalamocortical neurons and restored the average power of the thalamocortical spike trains in the band [3, 100] Hz, two indicators of restored thalamocortical activity. Furthermore, adaptive-DBS significantly decreased the energy requirements when compared with non-adaptive-DBS at the same frequency. Finally, 30- and 60-Hz-adaptive-DBS determined the maximal restoration of thalamocortical activity and outperformed high-frequency, non-adaptive-DBS. Overall, results suggest that a feedback-controlled, low-frequency DBS pattern may result in significant restoration of the thalamocortical encoding while lowering the energy requirements.