Cortical propagation tracks functional recovery after stroke

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. Author summary Millions of people worldwide suffer from long-lasting motor deficits caused by stroke. Very recently, the two basic therapeutic approaches, motor training and pharmacological intervention, have been combined in order to achieve a more efficient functional recovery. In this study, we analyze the neurophysiological activity in the brain of mice observed with in vivo calcium imaging before and after the induction of a stroke. We use a newly developed universal approach based on the temporal sequence of local activation in different brain regions to quantify three properties of global propagation patterns: duration, smoothness and angle. These innovative spatiotemporal propagation indicators allow us to track damage and functional recovery following stroke and to quantify the relative success of motor training, pharmacological inactivation, and a combination of both, compared to spontaneous recovery. We show that all three treatments reverse the alterations observed during the subacute phase right after stroke. We also find that combining motor training and pharmacological intervention does not restore pre-stroke features but rather leads to the emergence of new propagation patterns that, surprisingly, are even faster and smoother than the pre-stroke patterns.