Does Excessive Tonic Inhibition Cause Unstable Feedback in Parkinson’s Disease?

Parkinson’s disease is characterized by decreased dopamine in the basal ganglia, which causes excessive tonic inhibition of the thalamus. This excessive inhibition seems to explain decreased motor vigor in Parkinson’s disease, but whether it causes tremor remains unclear. This paper explores how inhibition may change closed-loop characteristics to determine how this established pathophysiology could produce tremor. First, single-neuron simulations establish the rate and time characteristics of increased tonic inhibition by adjusting the membrane time constant. These characteristics point towards two possible mechanisms for unstable feedback: information delay and decreased signal. Both cases create a mismatch between the closed-loop dynamics and the forward model that overcomes proprioceptive feedback delays. Overall, unstable feedback stemming from excessive tonic inhibition represents a unifying pathophysiology for the movement inhibiting and excitatory motor symptoms of Parkinson’s disease.