基於皮層－基底核－視丘迴路模擬對視覺刺激於巴金森氏症治療之機制研究

Abstract

巴金森氏症（Parkinson’s disease）是一種影響中樞神經系統的慢性神經退化性疾病。目前，巴金森氏症的病理假說認為逐漸減少從緻密黑質部供應的多巴胺改變基底核神經元的放電模式並產生與巴金森氏症相關的β頻段異常震盪。在本研究中，我們透過建立了由12種基於Hodgkin-Huxley的神經元電導模型，進一步組成皮質－基底核－視丘迴路（cortical-basal ganglia-thalamic loop，CBT loop），以模擬皮質－基底核－視丘迴路在兩種不同生理與病理狀態組合下的表現，包含在不同的疾病嚴重程度（基線／輕度／中度／重度）和在不同的意識狀態（清醒／非快速動眼期／麻醉）。除此之外，我們也藉由模擬來比較深腦刺激術（deep brain stimulation）和視覺刺激如何影響巴金森氏症的皮質－基底核－視丘迴路的放電模式。本研究發現1）視丘下核的深腦刺激術能完全阻斷視丘的上游訊號傳遞到其他下游腦區。2）視覺刺激能抑制視丘中的β頻段異常震盪並將正常的訊號傳遞到其他下游腦區。

Parkinson's disease (PD) is a chronic neurodegenerative disease affecting the central nervous system. The current pathological hypothesis suggests that the loss of dopaminergic input from substantia nigra pars compacta (SNc) altered basal ganglia neurons' firing pattern and eventually led to the emergence of a pathological beta band. Here, we build a whole Hodgkin-Huxley (HH) neuron-based cortical-basal ganglia-thalamic (CBT) loop model with twelve neuronal types as a library to simulate a combination of states, including PD progression states and cross-consciousness states. The simulation states include combinations of baseline (healthy)/three stages of PD and wake/non-rapid eye movement sleep/anesthesia. We also compare how deep brain stimulation (DBS) and visual stimulation affect the CBT loop dynamics in PD in silico. Our model shows that 1) subthalamic nucleus DBS can block all signals to further propagate from thalamic relay nuclei to other downstream circuitry. 2) optical stimulation can overcome the pathological beta wave in resting, wake thalamus, and propagate the desired signal to downstream circuitry.