The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamo-cortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through divergent intrathalamic circuits, and entrains thalamo-cortical pathways by means of propagating low-frequency oscillations beyond the restricted region of the lesion. Hence, pathological stroke-induced thalamo-cortical dynamics can be the source of diaschisis, and account for the dissociation between lesion location and non-specific symptoms of stroke such as neuropathic pain and hemispatial neglect.

新皮层（neocortex）与丘脑（thalamus）为感知、认知与动作提供核心底物，二者通过不同直接与间接通路相互连接，维持与清醒、睡眠等功能状态相关的特定动态特性。已有研究表明，兴奋性不足或皮层下抑制增强可破坏该系统，使丘脑核团陷入低频爆发的吸引子状态，并进一步驱动丘脑-皮层环路的同步活动，该现象也被称为丘脑皮层节律紊乱（thalamo-cortical dysrhythmia, TCD）。不过仍存在一个核心问题：是否存在起源于皮层的类似TCD的现象？例如在脑卒中场景中，皮层病灶可通过减弱向丘脑的兴奋性输入，破坏丘脑-皮层环路的交互作用，造成兴奋-抑制失衡，进而引发TCD状态。本研究通过对比21例急性缺血性脑卒中患者与17例年龄匹配的健康对照者的静息态脑电图（electroencephalogram, EEG）记录数据，验证了上述假说。结果显示，患者群体呈现出TCD的典型特征：脑电图功率谱中优势α频段峰值出现特征性下移，同时低频段（δ和θ频段）的功率显著升高。与TCD的常规观测结果不同，本研究中患者的β频段活动还出现了广泛性降低。为阐释该脑卒中诱导型TCD的发生机制，我们构建了一个具备生物学约束性的通用丘脑-皮层环路模型，借此明确了其涉及的特异性细胞与网络机制。模型结果显示，皮层区域的病灶会导致对应丘脑中继神经元的细胞膜持续超极化，进而使电压门控T型钙通道（voltage-gated T-type Ca²⁺ channels）去抑制，促使神经元从紧张性放电模式转变为病理性爆发模式。这种丘脑爆发活动可通过丘脑内的发散通路实现群体水平的活动同步，并通过将低频振荡传播至病灶以外的区域，实现对丘脑-皮层通路的同步驱动。因此，脑卒中诱导的病理性丘脑-皮层动态活动可作为远隔机能障碍（diaschisis）的源头，并可解释脑卒中病灶位置与非特异性症状（如神经病理性疼痛、半侧空间忽视）之间的分离现象。