Early changes in spatiotemporal dynamics of remapped circuits and global networks predict functional recovery after stroke in mice.

Significance: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

Aim: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

Approach: We used wide-field optical imaging, photothrombosis, and the cylinder-rearing assay to examine changes in neuronal circuit and network activity in the context of functional recovery after stroke.

Results: Larger strokes ablating $S{1}_{\mathrm{FP}}$ caused diffuse and widespread forepaw stimulus-evoked cortical activation, including contralesional regions evolving within 4 weeks post-stroke; smaller strokes resulted in more focused ipsilesional activation. Larger strokes decreased neuronal fidelity and bilateral coherence during stimulation of either the affected or unaffected forepaw within this 4-week period. Mice in the larger lesion group demonstrated hyperconnectivity within the contralesional hemisphere at the resting state. Greater degrees of remapping diffusivity, neuronal fidelity degradation, and hyperconnectivity predicted worse 8-week recovery after statistically controlling for the effect of infarct size.

Conclusions: These results suggest that diffuse patterns of remapping, and desynchronization and hyperconnectivity of cortical networks, evolving early after stroke may reflect maladaptive plasticity, predicting poor long-term functional recovery.