Human neuronal excitation/inhibition balance explains and predicts neurostimulation induced learning benefits.

Previous research has highlighted the role of the excitation/inhibition (E/I) ratio for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency transcranial 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-minute 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 (MRS)-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 versus 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.