The brain has a remarkable ability to undergo spontaneous self-repair in response to an injury or a cortical lesion. This dynamic and lasting restorative process involves a diverse array of neuroplastic mechanisms that are time and location dependent. Lesion-induced neuroplasticity is believed to involve neighboring intact neurons assuming the functional roles of the damaged ones, altering the brain’s activation map. Despite extensive research, there is still a lack of definitive evidence regarding neurons changing their functional response, leading to debates about the exact cellular mechanism of neuroplasticity. Conclusive evidence supporting or refuting functional remapping after stroke requires direct measurements and longitudinal tracking of neural activity at a single-neuron resolution and over chronic periods.

In this work, we employed multi-electrode arrays (NanoElectronic Threads) to record and longitudinally track both the sensory-evoked single-neuron spiking dynamics and population activity with high spatial specificity after a small-scale optically targeted stroke. Our multimodal measurement combined simultaneous laser speckle contrast imaging and hyperspectral reflectance spectroscopy, together with spatially distributed intracortical neural recordings. We found that while hemodynamic activation shifted following the cortical lesion, it no longer correlated with electrical neural activity. Direct neural recording showed a sustained suppression of evoked spiking activity near the lesioned infarct while an enhancement in the more distant cortical regions. Longitudinal tracking of individual neurons uncovered heterogeneous responses underlying the enhanced activity. We observed a distinct subset of neurons that demonstrated a significant upregulation in their sensory-evoked spiking activity which exhibited a stronger correlation with the overall population activity within the local cortical network, suggesting a potential restorative mechanism in response to the lesion. Contrary to the prevailing hypothesis of population-level changes in the peri-infarct region, our findings provide compelling evidence against this notion. Instead, our data reveal that lesion-induced plasticity at the single neuron level is manifested as a selective potentiation of pre-existing functional neurons.