Department of Mathematics and Computer Science, University of Barcelona, Barcelona, Spain.
Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy.
PLoS Comput Biol. 2021 May 17;17(5):e1008963. doi: 10.1371/journal.pcbi.1008963. eCollection 2021 May.
Stroke is a debilitating condition affecting millions of people worldwide. The development of improved rehabilitation therapies rests on finding biomarkers suitable for tracking functional damage and recovery. To achieve this goal, we perform a spatiotemporal analysis of cortical activity obtained by wide-field calcium images in mice before and after stroke. We compare spontaneous recovery with three different post-stroke rehabilitation paradigms, motor training alone, pharmacological contralesional inactivation and both combined. We identify three novel indicators that are able to track how movement-evoked global activation patterns are impaired by stroke and evolve during rehabilitation: the duration, the smoothness, and the angle of individual propagation events. Results show that, compared to pre-stroke conditions, propagation of cortical activity in the subacute phase right after stroke is slowed down and more irregular. When comparing rehabilitation paradigms, we find that mice treated with both motor training and pharmacological intervention, the only group associated with generalized recovery, manifest new propagation patterns, that are even faster and smoother than before the stroke. In conclusion, our new spatiotemporal propagation indicators could represent promising biomarkers that are able to uncover neural correlates not only of motor deficits caused by stroke but also of functional recovery during rehabilitation. In turn, these insights could pave the way towards more targeted post-stroke therapies.
中风是一种影响全球数百万人的致残性疾病。开发改进的康复治疗方法依赖于寻找适合跟踪功能损伤和恢复的生物标志物。为了实现这一目标，我们对中风前后小鼠的宽场钙成像获得的皮质活动进行时空分析。我们将自发恢复与三种不同的中风后康复范例进行了比较，即单独的运动训练、对侧药物失活以及两者的结合。我们确定了三个新的指标，这些指标能够跟踪运动诱发的全局激活模式如何因中风而受损，并在康复过程中演变：持续时间、平滑度和个体传播事件的角度。结果表明，与中风前的情况相比，中风后亚急性期皮质活动的传播速度减慢，且更加不规则。在比较康复范例时，我们发现接受运动训练和药物干预的小鼠，即唯一与广泛恢复相关的组，表现出的新传播模式比中风前更快、更平滑。总之，我们的新时空传播指标可能代表有前途的生物标志物，这些标志物不仅能够揭示中风引起的运动缺陷的神经相关性，还能够揭示康复期间的功能恢复。反过来，这些见解可能为更有针对性的中风后治疗铺平道路。
