Kelley Christopher R, Kauffman Jeffrey L
Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024:1-4. doi: 10.1109/EMBC53108.2024.10781501.
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.
帕金森病的特征是基底神经节中多巴胺减少，这会导致对丘脑的过度紧张性抑制。这种过度抑制似乎可以解释帕金森病中运动活力的下降，但它是否会导致震颤仍不清楚。本文探讨了这种抑制如何改变闭环特性，以确定这种既定的病理生理学如何产生震颤。首先，单神经元模拟通过调整膜时间常数来确定紧张性抑制增加的速率和时间特征。这些特征指向不稳定反馈的两种可能机制：信息延迟和信号减弱。这两种情况都会在闭环动力学和克服本体感受反馈延迟的前向模型之间产生不匹配。总体而言，由过度紧张性抑制引起的不稳定反馈代表了帕金森病运动抑制和兴奋性运动症状的统一病理生理学。
