Müller E J, van Albada S J, Kim J W, Robinson P A
School of Physics, The University of Sydney, Sydney, NSW 2006, Australia; Center for Integrative Brain Function, The University of Sydney, NSW 2006, Australia.
School of Physics, The University of Sydney, Sydney, NSW 2006, Australia; Institute of Neuroscience and Medicine (INM-6) and Institute for Advanced Simulation (IAS-6) and JARA BRAIN Institute I, Jülich Research Center, Jülich, Germany.
J Theor Biol. 2017 Sep 7;428:132-146. doi: 10.1016/j.jtbi.2017.06.016. Epub 2017 Jun 17.
The mechanisms underlying pathologically synchronized neural oscillations in Parkinson's disease (PD) and generalized epilepsies are explored in parallel via a physiologically-based neural field model of the corticothalamic-basal ganglia (CTBG) system. The basal ganglia (BG) are approximated as a single effective population and their roles in the modulation of oscillatory dynamics of the corticothalamic (CT) system and vice versa are analyzed. In addition to normal EEG rhythms, enhanced activity around 4 Hz and 20 Hz exists in the model, consistent with the characteristic frequencies observed in PD. These rhythms result from resonances in loops formed between the BG and CT populations, analogous to those that underlie epileptic oscillations in a previous CT model, and which are still present in the combined CTBG system. Dopamine depletion is argued to weaken the dampening of these loop resonances in PD, and network connections then explain the significant coherence observed between BG, thalamic, and cortical population activity around 4-8 Hz and 20 Hz. Parallels between the afferent and efferent connection sites of the thalamic reticular nucleus (TRN) and BG predict low dopamine to correspond to a reduced likelihood of tonic-clonic (grand mal) seizures, which agrees with experimental findings. Furthermore, the model predicts an increased likelihood of absence (petit mal) seizure resulting from pathologically low dopamine levels in accordance with experimental observations. Suppression of absence seizure activity is demonstrated when afferent and efferent BG connections to the CT system are strengthened, which is consistent with other CTBG modeling studies. The BG are demonstrated to have a suppressive effect on activity of the CTBG system near tonic-clonic seizure states, which provides insight into the reported efficacy of current treatments in BG circuits. Sleep states of the TRN are also found to suppress pathological PD activity in accordance with observations. Overall, the findings demonstrate strong parallels between coherent oscillations in generalized epilepsies and PD, and provide insights into possible comorbidities.
通过基于生理学的皮质丘脑 - 基底神经节（CTBG）系统神经场模型，并行探究帕金森病（PD）和全身性癫痫中病理性同步神经振荡的潜在机制。将基底神经节（BG）近似为单个有效群体，并分析其在调节皮质丘脑（CT）系统振荡动力学中的作用，反之亦然。除了正常的脑电图节律外，模型中还存在4Hz和20Hz附近增强的活动，这与在PD中观察到的特征频率一致。这些节律源于BG和CT群体之间形成的环路中的共振，类似于先前CT模型中癫痫振荡的基础，并且在组合的CTBG系统中仍然存在。多巴胺耗竭被认为会削弱PD中这些环路共振的抑制作用，然后网络连接解释了在4 - 8Hz和20Hz附近BG、丘脑和皮质群体活动之间观察到的显著相干性。丘脑网状核（TRN）和BG的传入和传出连接位点之间的相似性预测低多巴胺对应于强直 - 阵挛（大发作）癫痫发作的可能性降低，这与实验结果一致。此外，该模型预测，根据实验观察，多巴胺水平病理性降低会导致失神（小发作）癫痫发作的可能性增加。当加强BG与CT系统的传入和传出连接时，失神癫痫发作活动受到抑制，这与其他CTBG建模研究一致。已证明BG对强直 - 阵挛癫痫发作状态附近的CTBG系统活动具有抑制作用，这为目前BG回路治疗的报道疗效提供了见解。还发现TRN的睡眠状态根据观察结果抑制病理性PD活动。总体而言，这些发现表明全身性癫痫和PD中的相干振荡之间存在强烈相似性，并为可能的合并症提供了见解。
