Department of Psychology, University of Toronto, Toronto, ON M5S 3G3, Canada.
Rotman Research Institute, Baycrest Health Sciences, Toronto, ON M6A 2E1, Canada.
Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2409345121. doi: 10.1073/pnas.2409345121. Epub 2024 Nov 6.
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.
中风导致神经活动明显和广泛减慢。尽管数十年来一直在探索这些异常神经动力学及其相关的功能障碍，但它们的原因仍在很大程度上不清楚。为了弥补这一理解上的差距，我们应用神经生理皮质丘脑电路模型来模拟从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进行比较，患者在受损半球显示出明显较低的丘脑内抑制，尽管丘脑本身没有直接损伤。我们假设这种去抑制作用可能与丘脑的继发性退化有关，文献中有越来越多的证据表明了这一点。进一步的分析证实，频谱减慢与对侧丘脑的总体继发性退化显著相关，包括丘脑体积减小、组织微结构改变和血流量减少。至关重要的是，这种相关性是通过模型估计的丘脑去抑制来介导的，这表明继发性丘脑退化与异常大脑动力学之间存在因果关系，即通过丘脑去抑制。最后，丘脑退化与认知和语言功能较差显著相关，但与病变体积无关，这表明丘脑损伤可能导致中风后残疾的个体差异增加。总的来说，我们的发现表明，经常观察到的中风后减速反映了皮质丘脑回路动力学的破坏，这是由于继发性丘脑功能障碍所致，并强调了丘脑作为理解和潜在治疗中风后大脑功能障碍的重要目标。
