Not Only a Matter of Age: Machine Learning-Based Characterization of the Differential Effect of Brain Stimulation on Skill Acquisition

Brain stimulation shows potential at enhancing cognitive and motor functions in humans. However, multiple studies assessing its effects on behavior show heterogeneous results, especially in healthy older subjects. We propose a new method to predict an individual’s likelihood and the magnitude of the benefit from stimulation, based on the baseline performance of a sequential motor task, framed in the context of their age. Our results show a differential effect of stimulation, in which individuals with less efficient learning mechanisms benefit from stimulation, while those possessing optimal learning strategies resent a detrimental effect. Importantly, this differential effect was determined by one’s ability to integrate task-relevant information at the early stages of training, and not the age. This study paves the way towards the personalized application of stimulation to maximize its effects, and constitutes the first steps to implement an individualized translational clinical intervention, based on the state of the neural system. Teaser Age notwithstanding, brain stimulation is most effective in deficient neural systems, while being detrimental to optimal systems Visual abstract Main finding Anodal transcranial direct current stimulation (atDCS), applied over the hand representation of the motor cortex concomitant to the training of a sequential motor sequence, has differential effects as a function of the recipient’s ability to integrate task-relevant information at the early stages of training. Stimulation benefits individuals with seemingly less efficient learning mechanisms, enabling the rapid storage of the spatial coordinates of the motor sequence and an accelerated optimization of the accuracy of execution. In contrast, individuals possessing optimal learning mechanisms experience detrimental effects of stimulation, leading to drops in the accuracy of execution.