Acute Slow Oscillation Power as a Biomarker of Injury Severity After Photothrombotic Stroke: Dissociation from Week 1 Functional Recovery

Cortical slow oscillations (SOs; 0.1-1.0 Hz) are suppressed after ischemic stroke, and their recovery is often read as evidence of circuit reorganization and functional restoration. Whether SO recovery is coupled to behavioral improvement, and whether pre-stroke network organization shapes recovery, has not been tested within individual animals. Using longitudinal wide-field calcium imaging in Thy1-GCaMP6f mice (n = 25), we tracked ipsilateral and contralateral SO power across baseline, 24 hours, and one week after photothrombotic stroke of the left somatosensory forepaw cortex, classifying animals by the presence (STI+; n = 14) or absence (STI-; n = 11) of secondary thalamic injury (STI). Acute ipsilateral SO power was markedly suppressed and tracked concurrent behavioral deficit ({rho} = -0.718, p < 0.001), capturing dysfunction beyond lesion volume (partial {rho} = -0.448, p = 0.025). By one week SO power had recovered, yet this recovery was dissociated from forelimb use. Week 1 SO power showed no association with behavior in any region or hemisphere (all |{rho}| [&le;] 0.074, all p > 0.5), and STI+ and STI- animals recovered SO equivalently despite STI+ animals remaining more impaired (p = 0.011). In contrast, pre-stroke SO laterality predicted week 1 forelimb use independent of infarct size ({rho} = -0.518, p = 0.008; partial {rho} = -0.446, p = 0.026). Acute SO suppression thus tracks injury severity beyond infarct volume, but its recovery does not track functional recovery; instead, pre-stroke interhemispheric SO balance predicts outcome, identifying pre-injury brain state as an underappreciated prognostic factor. Significance StatementSlow oscillations are suppressed by stroke and recover over time, and that recovery is often read as a sign of functional repair. Whether oscillatory recovery actually tracks behavioral recovery had not been tested within individual animals. Tracking slow oscillation power and forelimb use longitudinally, we show that acute suppression marks injury severity beyond lesion size, but that recovery of slow oscillation power over the first week does not track recovery of forelimb use: animals with good and poor outcomes recover oscillations equivalently. What predicts recovery is instead the interhemispheric balance of slow oscillation power (its relative distribution across the two hemispheres) present before the stroke. These results separate oscillatory recovery from functional recovery and point to pre-injury brain state as a prognostic factor.