Explaining and Predicting the Effects of Neurostimulation via Neuronal Excitation/Inhibition

Previous research has highlighted the role of the excitation/inhibition ratio (E/I) for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency random noise stimulation (tRNS)--an excitatory form of neurostimulation--on learning. We examined the E/I as a potential mechanism and studied whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent as its putative marker. In addition to manipulating E/I using tRNS, we also manipulated the level of learning (learning/overlearning) that has been shown to influence E/I. Participants (n=102) received either sham stimulation or 20 min tRNS over the dorsolateral prefrontal cortex (DLPFC) during a mathematical learning task. We showed that tRNS increased E/I, as reflected by the aperiodic exponent, and that lower E/I predicted greater benefit from tRNS specifically for the learning task. In contrast to previous Magnetic Resonance Spectroscopy-based E/I studies, we found no effect of the level of learning on E/I. A further analysis using a different data set suggest that both measures of E/I (EEG vs MRS) may reflect, at least partly, different biological mechanisms. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding provides better opportunities for augmented learning and personalized interventions.