Region-specific non-rapid eye movement delta activity is associated with stroke recovery

Abstract

Neural activity in the delta range (1.0-4.5 Hz) during non-rapid eye movement (NREM) sleep is crucial for brain plasticity and overall brain health. Recent research has shown that changes in NREM delta activity can occur locally, and activity can vary across different brain regions. Ischemic stroke results in focal brain injury and long-term disability. While sleep disruption during the acute phase of stroke is known to hinder recovery, the relationship between region-specific changes in NREM delta activity and functional recovery remains poorly understood. To investigate these localized changes in NREM delta activity with high spatial resolution, we utilized wide-field optical imaging (WFOI) in mice that expressed GCaMP6f, a fluorescent calcium indicator, in cortical excitatory pyramidal neurons. Sleep was longitudinally recorded before and at 24 hours, 1 week, and 4 weeks after photothrombotic stroke in the left somatosensory forepaw cortex. In the acute phase of stroke (24 hours post-stroke), mice exhibited decreased delta activity in the infarct and peri-infarct regions during NREM sleep. Increased delta activity in the contralesional hemisphere and decreased delta activity in the perilesional region during NREM sleep in the acute phase were associated with poor behavioral recovery, as measured by performance on the cylinder rearing test. These findings suggest that region-specific NREM delta activity may play a crucial role in stroke recovery and warrant further investigation to determine whether modulating delta activity in targeted brain areas during NREM sleep could aid recovery.

Keywords: GCaMP-HS; brain injury; ischemic stroke; mouse model; optical imaging; sleep, NREM; sleep, REM; sleep, slow-wave; somatosensory cortex; wakefulness.