Senft Valentin, Stewart Terrence C, Bekolay Trevor, Eliasmith Chris, Kröger Bernd J
Medical School, RWTH Aachen University, Aachen, Germany.
Centre for Theoretical Neuroscience, University of Waterloo, Waterloo, ON, Canada.
Front Comput Neurosci. 2018 Jun 6;12:41. doi: 10.3389/fncom.2018.00041. eCollection 2018.
Parkinson's disease affects many motor processes including speech. Besides drug treatment, deep brain stimulation (DBS) in the subthalamic nucleus (STN) and globus pallidus internus (GPi) has developed as an effective therapy. We present a neural model that simulates a syllable repetition task and evaluate its performance when varying the level of dopamine in the striatum, and the level of activity reduction in the STN or GPi. The Neural Engineering Framework (NEF) is used to build a model of syllable sequencing through a cortico-basal ganglia-thalamus-cortex circuit. The model is able to simulate a failing substantia nigra pars compacta (SNc), as occurs in Parkinson's patients. We simulate syllable sequencing parameterized by (i) the tonic dopamine level in the striatum and (ii) average neural activity in STN or GPi. With decreased dopamine levels, the model produces syllable sequencing errors in the form of skipping and swapping syllables, repeating the same syllable, breaking and restarting in the middle of a sequence, and cessation ("freezing") of sequences. We also find that reducing (inhibiting) activity in either STN or GPi reduces the occurrence of syllable sequencing errors. The model predicts that inhibiting activity in STN or GPi can reduce syllable sequencing errors in Parkinson's patients. Since DBS also reduces syllable sequencing errors in Parkinson's patients, we therefore suggest that STN or GPi inhibition is one mechanism through which DBS reduces syllable sequencing errors in Parkinson's patients.
帕金森病会影响包括言语在内的许多运动过程。除药物治疗外，丘脑底核（STN）和苍白球内侧部（GPi）的深部脑刺激（DBS）已发展成为一种有效的治疗方法。我们提出了一个模拟音节重复任务的神经模型，并在改变纹状体中多巴胺水平以及STN或GPi活动减少水平时评估其性能。神经工程框架（NEF）用于通过皮质-基底神经节-丘脑-皮质回路构建音节排序模型。该模型能够模拟帕金森病患者中出现的黑质致密部（SNc）功能衰退。我们模拟了由（i）纹状体中的多巴胺张力水平和（ii）STN或GPi中的平均神经活动参数化的音节排序。随着多巴胺水平降低, 该模型会产生音节排序错误，表现为跳过和交换音节、重复相同音节、在序列中间中断并重新开始以及序列停止（“冻结”）。我们还发现，降低（抑制）STN或GPi中的活动会减少音节排序错误的发生。该模型预测，抑制STN或GPi中的活动可以减少帕金森病患者的音节排序错误。由于DBS也能减少帕金森病患者的音节排序错误，因此我们认为STN或GPi抑制是DBS减少帕金森病患者音节排序错误的一种机制。
