Cortical propagation tracks functional recovery after stroke

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / physiopathology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Recovery of Function / physiology
  • Stroke / physiopathology*
  • Stroke Rehabilitation / methods*

Grant support

This project has received funding from the H2020 EXCELLENT SCIENCE - European Research Council (ERC) under grant agreement ID n. 692943 BrainBIT and from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 785907 (HBP SGA2) [Grant recipient: F.S.P.]. This research was supported by the EBRAINS research infrastructure, funded from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3) [Grant recipient: F.S.P.]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.