Neuromuscular Systems Lab, School of Electrical & Electronic Engineering, University College Dublin, Dublin, Ireland.
J Neural Eng. 2021 Apr 6;18(5). doi: 10.1088/1741-2552/abee50.
. High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) suppresses excessive beta band (∼13-30 Hz) activity of the motor cortex in Parkinson's disease (PD). While the mechanisms of action of STN DBS are not well-understood, strong evidence supports a role for cortical network modulating effects elicited by antidromic activation of cortical axons via the hyperdirect pathway.. A spiking model of the thalamo-cortical microcircuit was developed to examine modulation of cortical network activity by antidromic STN DBS, mediated by direct activation of deep pyramidal neurons (PNs) and subsequent indirect activation of other thalamo-cortical structures.. Increasing synaptic coupling strength from cortical granular to superficial layers, from inhibitory neurons to deep PNs, and from thalamus reticular to relay cells, along with thalamocortical connection strength, accompanied by reduced coupling from cortical superficial to granular layers, from thalamus relay cells to reticular neurons, and corticothalamic connection strength, led to increased beta activity and neural synchrony, as observed in PD. High frequency DBS desynchronized correlated neural activity, resulting in clusters of both excited and inhibited deep cortical PNs. The emergence of additional frequency components in the local field potential (LFP), and increased power at subharmonics of the DBS frequency as observed in patients with dyskinesia during DBS, occurred under different stimulus amplitudes and frequencies. While high-frequency (>100 Hz) DBS suppressed the LFP beta power, low-frequency (<40 Hz) DBS increased beta power when more than 10% of PNs were activated, but reduced the total beta power at lower levels of neural activation.. The results suggest a potential mechanism for experimentally observed alterations in cortical neural activity during DBS via the propagation of DBS stimuli throughout the cortical network, modulated by short-term synaptic plasticity, and the emergence of resonance due to interaction of DBS with existing M1 rhythms by engaging feedforward-feedback loops.
. 高频深部脑刺激（DBS）于丘脑底核（STN）抑制帕金森病（PD）患者运动皮层过度的β频带（∼13-30 Hz）活动。虽然 STN DBS 的作用机制尚未完全清楚，但有强有力的证据支持通过直接激活皮层轴突的逆行激活来调节皮层网络的作用，这种作用通过超直接通路产生。.. 开发了丘脑皮质微电路的尖峰模型，以检查通过直接激活深皮质神经元（PNs）和随后间接激活其他丘脑皮质结构，逆行 STN DBS 对皮质网络活动的调制作用。.. 增加从皮层颗粒层到浅层的突触耦合强度，从抑制性神经元到深 PN 的强度，以及从丘脑网状到中继细胞的强度，以及丘脑皮质连接强度，同时减少从皮层浅层到颗粒层的耦合，从丘脑中继细胞到网状神经元的耦合，以及皮质丘脑连接强度，导致β活动和神经同步增加，如 PD 中观察到的那样。高频 DBS 使相关神经活动去同步化，导致深皮质 PN 兴奋和抑制的簇出现。局部场电位（LFP）中出现额外的频率成分，以及在患者出现运动障碍时 DBS 期间观察到 DBS 频率的次谐波增加的功率，发生在不同的刺激幅度和频率下。虽然高频（>100 Hz）DBS 抑制了 LFP β功率，但当超过 10%的 PN 被激活时，低频（<40 Hz）DBS 增加了 β功率，但在较低的神经激活水平下降低了总 β功率。.. 结果表明，通过 DBS 刺激在皮层网络中的传播，通过短期突触可塑性进行调制，以及由于 DBS 与现有的 M1 节律相互作用而产生的共振的出现，通过前馈-反馈回路参与，通过 DBS 观察到的皮层神经活动的改变的潜在机制。
