Stroke causes pronounced and widespread slowing of neural activity. Despite decades of work exploring these abnormal neural dynamics and their associated functional impairments, their causes remain largely unclear. To close this gap in understanding, we applied a neurophysiological corticothalamic circuit model to simulate magnetoencephalography (MEG) power spectra recorded from chronic stroke patients. Comparing model-estimated physiological parameters to those of controls, patients demonstrated significantly lower intrathalamic inhibition in the lesioned hemisphere, despite the absence of direct damage to the thalamus itself. We hypothesized that this disinhibition could instead be related to secondary degeneration of the thalamus, for which growing evidence exists in the literature. Further analyses confirmed that spectral slowing correlated significantly with overall secondary degeneration of the ipsilesional thalamus, encompassing decreased thalamic volume, altered tissue microstructure, and decreased blood flow. Crucially, this relationship was mediated by model-estimated thalamic disinhibition, suggesting a causal link between secondary thalamic degeneration and abnormal brain dynamics via thalamic disinhibition. Finally, thalamic degeneration was correlated significantly with poorer cognitive and language outcomes, but not lesion volume, reinforcing that thalamus damage may account for additional individual variability in poststroke disability. Overall, our findings indicate that the frequently observed poststroke slowing reflects a disruption of corticothalamic circuit dynamics due to secondary thalamic dysfunction, and highlights the thalamus as an important target for understanding and potentially treating poststroke brain dysfunction.

中文翻译：

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继发性丘脑功能障碍是慢性卒中中异常大规模神经动力学的基础


中风会导致神经活动明显而广泛的减慢。尽管几十年来一直在探索这些异常的神经动力学及其相关的功能障碍，但它们的原因在很大程度上仍不清楚。为了缩小这一理解差距，我们应用了神经生理学皮质丘脑回路模型来模拟慢性中风患者记录的脑磁图 （MEG） 功率谱。将模型估计的生理参数与对照组的生理参数进行比较，尽管没有对丘脑本身的直接损伤，但患者在病变半球的丘脑内抑制显著降低。我们假设这种去抑制可能与丘脑的继发性变性有关，文献中对此有越来越多的证据。进一步的分析证实，频谱减慢与同侧丘脑的整体继发性变性显著相关，包括丘脑体积减少、组织微观结构改变和血流减少。至关重要的是，这种关系是由模型估计的丘脑去抑制介导的，表明继发性丘脑变性与通过丘脑去抑制的异常大脑动力学之间存在因果关系。最后，丘脑变性与较差的认知和语言结果显著相关，但与病变体积无关，这加强了丘脑损伤可能是中风后残疾的额外个体变异性的原因。总体而言，我们的研究结果表明，经常观察到的中风后减慢反映了继发性丘脑功能障碍导致皮质丘脑回路动力学的中断，并强调丘脑是理解和可能治疗中风后脑功能障碍的重要目标。