Human Neuronal Excitation/Inhibition Balance Explains and Predicts Neurostimulation Induced Learning Benefits

Abstract

Previous research has highlighted the role of the excitation/inhibition ratio (E/I) for typical and atypical development, mental health, cognition, and learning. Parallel 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 whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent. 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. One hundred and two participants received either sham stimulation or 20 min DLPFC tRNS during a mathematical learning task. We showed a lower aperiodic exponent, which reflects higher E/I, after tRNS, and that higher baseline aperiodic exponent, which reflects lower E/I, predicted greater benefit from tRNS specifically for the learning task. In contrast to previous MRS-based E/I studies, we found no effect of the learning manipulation on E/I. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding could provide stronger potential to augment learning. At the same time, we offer new insights on the quantification of E/I using EEG vs MRS to foster better theoretical understanding and its utilisation in future research.

Digital twins for understanding mechanisms of learning disabilities: Personalized deep neural networks reveal impact of neuronal hyperexcitability

“…Thus, neural excitability maybe a significant contributor to suboptimal performance levels observed in children with MLD. These results resonate with empirical research on Glutamate/GABA levels indicating excitatoryinhibitory imbalances 41,43,56,57 , and intrinsic fMRI hyperactivity and hyperconnectivity 34 , as well as task-related hyperactivity and hyperconnectivity in MLD 18 . Together, our computational modeling of pDNNs and empirical findings reinforce the notion that neural excitability plays a crucial role in learning and may be a key neurophysiological factor underlying MLD.…”

“…Our study brings to light the significant impact of neural excitability and hyper-excitability on learning processes, which we evaluated here in the context of MLD. Theoretical models propose that E/I imbalances could disrupt functional neural circuitry, potentially leading to a range of neurodevelopmental disorders, including MLD 41,43,56,57 . By focusing on E/I imbalance, our pDNN model provides a more precise understanding of the neurobiological underpinnings of learning disabilities.…”

“…Individuals lacking in mathematical education have also been shown to demonstrate lower inhibition in brain regions relevant to reasoning and learning 36 . Recent studies which attempt to rectify E/I imbalance by using neurostimulation have shown that E/I balance modulates the amount of benefit that can be obtained from neurostimulation [41][42][43] , and can be a marker for neurostimulation based efficacy and learning 41 . Despite these advances, the neurophysiological mechanisms underlying MLD, the sufficiency of establishing E/I imbalances as contributing factors towards MLD, and the mechanisms via which such imbalances may cause learning difficulties, remain speculative, primarily due to the correlative nature of brain imaging studies.…”

“…Moreover, as reviewed above, task-related hyperactivation and intrinsic hyper-fluctuations observed in children with MLD suggest that E/I imbalance may be a key underlying neurophysiological mechanism. The concept of E/I imbalance as a putative neural mechanism underlying learning disabilities is suggested by both theoretical models and empirical research 41,43,53,[55][56][57] . E/I balance is a fundamental aspect of neural processing, playing a crucial role in shaping neural network dynamics and cognitive function [52][53][54][55] .…”

Transcranial random noise stimulation combined with cognitive training for treating ADHD: a randomized, sham-controlled clinical trial

“…While this shift could be attributed to various factors, it highlights an imbalance in E/I in cortical circuits which is related to disrupted information processing [60]. E/I has been proposed as a neural marker for stimulation efficacy [61,62], and could reliably predict ADHD likelihood in early development [59]. The only study to date which examined the effect of tRNS on aperiodic activity found that tRNS increases E/I and is associated with cognitive improvement in adults without ADHD [62].…”