Non‐invasive Flicker Neurostimulation Boosts Resilience to Psychological Stress

Abstract

AbstractBackgroundChronic stress promotes life‐long risk for neuropsychiatric decline by increasing neuroinflammation and disrupting synaptic health and plasticity. Our lab and others have recently demonstrated that non‐invasive gamma sensory flicker stimulation modulates inflammatory signaling, restores microglia function and improves cognitive performance in mice models of Alzheimer’s disease (AD). However, no research to date has studied the effects of flicker in the context of stress. Accordingly, our goal for this study was to determine how sensory flicker stimulation mitigates neuropsychiatric‐like behavioral deficits and rescue glia and synapse pathology following chronic stress.MethodDaily flicker intervention was introduced concomitantly with daily stress exposure (28 days) at multiple frequencies in male and female C57BL6 and Thy1‐GFP mice (n = 6/group per sex). The mice were then tested for anxiety‐like and anhedonia using a range of behavioral tests. Next, we quantified spine density changes in Thy1‐GFP mice and quantified GFAP‐labeled astrocyte morphology change, a reliable proxy for astrocyte reactivity, in the medial PFC using the semi‐automated Imaris imaging software to determine synaptic health and inflammatory profile, respectively.ResultWe show for the first time that stress‐induced morphological changes in the medial PFC are modulated in a sex‐, and frequency‐specific manner that coincides with behavioral resilience in stressed mice. Our findings indicates that audio‐visual flicker protect against stress‐induced behavioral deficits (p<0.0001) and improves neuroinflammation (p<0.01) in a sex‐ and frequency‐specific manner.ConclusionTogether, these findings show frequency tunable flicker intervention improves stress pathology and may prevent neuropsychiatric health decline in conditions with sex dimorphic symptoms and prevalence.