Multi-site stimulation of subthalamic nucleus diminishes thalamocortical relay errors in a biophysical network model

This paper presents results on a computational study of how multi-site stimulation of the subthalamic nucleus (STN), within the basal ganglia, can improve the fidelity of thalamocortical (TC) relay in a parkinsonian network model. In the absence of stimulation, the network model generates activity featuring synchronized bursting by clusters of neurons in the STN and internal segment of the globus pallidus (GPi), as occurs experimentally in parkinsonian states. This activity yields rhythmic inhibition from GPi to TC neurons, which compromises TC relay of excitatory inputs. We incorporate two types of multi-site STN stimulation into the network model. One stimulation paradigm features coordinated reset pulses that are on for different subintervals of each period at different sites. The other is based on a filtered version of the local field potential recorded from the STN population. Our computational results show that both types of stimulation significantly diminish TC relay errors; the former reduces the rhythmicity of the net GPi input to TC neurons and the latter reduces, but does not eliminate, STN activity. Both types of stimulation represent promising directions for possible therapeutic use with Parkinson’s disease patients.