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 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.