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bioRxiv · 10.1101/2020.11.30.404269

A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation

Milosevic, L.·Kalia, S. K.·Hodaie, M.·Lozano, A. M.·Popovic, M. R.·Hutchison, W. D.·Lankarany, M.
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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.

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Milosevic, L., Kalia, S. K., Hodaie, M., Lozano, A. M., Popovic, M. R., Hutchison, W. D., Lankarany, M.. 2020-12-02. A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation. https://doi.org/10.1101/2020.11.30.404269

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