Modafinil Modulation of Oscillatory and Aperiodic Brain Activity in Rats Across Wakefulness and Subsequent Sleep

Abstract Cortical states shape sensory processing, decision-making, and behavior, and are characterized by distinct patterns of neuronal oscillatory activity. Pharmacological agents can modulate these states and their underlying electrophysiological signatures. Modafinil is a widely used wake-promoting agent and cognitive enhancer, but its effects on cortical oscillations are not fully understood. In this study, we evaluated the effect of modafinil on cortical activity during wakefulness and subsequent sleep. Ten male Wistar rats were implanted with electrocorticographic electrodes and recorded following oral administration of modafinil or its vehicle. Our results show that modafinil increased wakefulness in a dose-dependent manner, with doses of 200 and 300 mg/kg producing prolonged wake episodes and reducing hypnogram complexity. During wakefulness, modafinil enhanced gamma-band power in anterior cortices, an effect primarily driven by increases in the aperiodic rather than oscillatory components. Although no sleep rebound was observed, subsequent NREM sleep exhibited increased delta power, particularly in anterior regions, indicating heightened sleep pressure. In conclusion, our findings demonstrate that modafinil-induced wakefulness is associated with an enhanced aperiodic gamma band component at the anterior cortices in the EEG. Furthermore, modafinil modulates sleep homeostasis by enhancing NREM sleep intensity rather than extending its duration.