Abstract
With the growing interest in the expansion of deep brain stimulation indications, we aimed to provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on human neuronal activity. Experimentally, we demonstrated microstimulation-evoked excitatory neuronal responses in the ventral intermediate nucleus and reticular thalamus, and inhibitory responses in the subthalamic nucleus and substantia nigra pars reticulata; hypothesized to be the result of simultaneous activations of convergent afferent inputs. Higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression; hypothesized to be mediated by synaptic depression. These experimental findings were reproduced by a computational framework in which relative distributions of convergent excitatory/inhibitory afferents were embedded within a model of short-term synaptic plasticity for the prediction of site-specific and frequency-dependent responses to extracellular stimulation. This theoretical framework may aid in the design of physiologically-informed stimulation paradigms in existing or prospective deep brain stimulation indications.
Competing Interest Statement
S.K.K., M.H., W.D.H. have received honoraria, travel funds, and/or grant support from Medtronic (not related to this work). A.M.L. has received honoraria, travel funds, and/or grant support from Medtronic, Boston Scientific, St. Jude-Abbott, and Insightec (not related to this work). M.R.P. is a shareholder in MyndTec Inc. A.M.L. is a co-founder of Functional Neuromodulation Ltd. L.M. and M.L. have no financial disclosures.