Objective. Cognitive and memory impairments are common sequelae after stroke, yet how middle cerebral artery (MCA) stroke chronically affects the neural activity of the hippocampus, a brain region critical for memory but remote from the stroke epicenter, is poorly understood. Environmental enrichment (EE) improves cognition following stroke; however, the electrophysiology that underlies this behavioral intervention is still elusive. Approach. We recorded extracellular local field potentials simultaneously from sensorimotor cortex and hippocampus in rats during urethane anesthesia following MCA occlusion and subsequent EE treatment. Main results. We found that MCA stroke significantly impacted the electrophysiology in the hippocampus, in particular it disrupted characteristics of sharp-wave associated ripples (SPW-Rs) altered brain state, and disrupted phase amplitude coupling (PAC) within the hippocampus and between the cortex and hippocampus. Importantly, we show that EE mitigates stroke-induced changes to SPW-R characteristics but does not restore hippocampal brain state or PAC. Significance. These results begin to uncover the complex interaction between cognitive deficit following stroke and EE treatment, providing a testbed to assess different strategies for therapeutics following stroke.

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Cognitive and memory impairments are common sequelae after stroke, yet it is not well understood how middle cerebral artery (MCA) stroke chronically affects the neural activity of the hippocampus, a brain region critical for memory function but remote from the stroke epicenter. Environmental enrichment (EE) has been shown to improve cognition following stroke; however, the electrophysiology that underlies this behavioral intervention is still elusive. We recorded local field potentials simultaneously from sensorimotor cortex and hippocampus in rats following MCA occlusion and subsequent EE treatment. We found that stroke increased duration and power of sharp-wave associated ripples (SPW-Rs), altered brain state, and disrupted phase amplitude coupling (PAC) within the hippocampus and between the cortex and hippocampus. EE counteracted stroke-induced increase in SPW-R characteristics but did not restore hippocampal brain state or PAC. Our results suggest that these brain oscillatory changes are novel biomarkers underlying stroke-induced cognitive impairment and the recovery from EE.

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.