BrainWAVE: A Flexible Method for Noninvasive Stimulation of Brain Rhythms across Species

Abstract

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are limited. Accordingly, we recently introduced a noninvasive stimulation approach using flickering lights and sounds (“flicker”). Flicker drives rhythmic activity in deep and superficial brain regions. Gamma flicker spurs immune function, clears pathogens, and rescues memory performance in mice with amyloid pathology. Here we present substantial improvements to this approach that is flexible, user-friendly, and generalizable across multiple experimental settings and species. We present novel open-source methods for flicker stimulation across rodents and humans. We demonstrate rapid, cross-species induction of rhythmic activity without behavioral confounds in multiple settings from electrophysiology to neuroimaging. This flicker approach provides an exceptional opportunity to discover the therapeutic effects of brain rhythms across scales and species.Significance StatementDespite many studies showing abnormal brain rhythms in multiple diseases, limited means to target deep brain regions noninvasively has restricted the therapeutic potential of driving brain rhythms. Accordingly, we developed a noninvasive millisecond precise sensory stimulation to drive brain rhythms. Here we introduce for the first time newly developed open-source software and instructions for building, testing, debugging, and using BrainWAVE (Brain Wide-spectrum Audio/Visual Exposure) stimulation. We demonstrate BrainWAVE stimulation across multiple species and different experimental settings. These methods constitute a customizable, open-source, accessible, and non-invasive technology that stimulates brain oscillations to causally test how rhythmic brain activity impacts brain function.