Disturbed laterality of non-rapid eye movement sleep oscillations in post-stroke human sleep: a pilot study

Sleep is known to promote recovery post-stroke. However, there is a paucity of data profiling sleep oscillations in the post-stroke human brain. Recent rodent work showed that resurgence of physiologic spindles coupled to sleep slow oscillations (SOs) and concomitant decrease in pathological delta (delta) waves is associated with sustained motor performance gains during stroke recovery. The goal of this study was to evaluate bilaterality of non-rapid eye movement (NREM) sleep-oscillations (namely SOs, delta-waves, spindles, and their nesting) in post-stroke patients vs. healthy control subjects. We analyzed NREM-marked electroencephalography (EEG) data in hospitalized stroke-patients (n = 5) and healthy subjects (n = 3). We used a laterality index to evaluate symmetry of NREM oscillations across hemispheres. We found that stroke subjects had pronounced asymmetry in the oscillations, with a predominance of SOs, delta-waves, spindles, and nested spindles in affected hemisphere, when compared to the healthy subjects. Recent preclinical work classified SO-nested spindles as restorative post-stroke and delta-wave-nested spindles as pathological. We found that the ratio of SO-nested spindles laterality index to delta-wave-nested spindles laterality index was lower in stroke subjects. Using linear mixed models (which included random effects of concurrent pharmacologic drugs), we found large and medium effect size for delta-wave nested spindle and SO-nested spindle, respectively. Our results in this pilot study indicate that considering laterality index of NREM oscillations might be a useful metric for assessing recovery post-stroke and that factoring in pharmacologic drugs may be important when targeting sleep modulation for neurorehabilitation post-stroke.