Optimizing the efficacy of transcranial direct current stimulation on cortical neuroplasticity based on a neurovascular coupling model

Abstract

Our understanding of how our brain learns and retains new motor skills has evolved significantly over the last several decades. One significant break-through has been in the area of neuroimaging, where scientists are now able observe brain activity in real-time while humans are asked to learn or perform various behaviors. Simultaneously, measurement devices like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG) can be used to noninvasively visualize and quantify the brain regions that are relevantly involved with the performed action or learning process. But the story does not stop there: in recent years, new technology has emerged that allows researchers and clinicians to interact with vital brain regions and networks by using low intensities of electric current stimulation. This weak form of stimulation, called transcranial direct current stimulation, or tDCS, is remarkable in that it can induce long-term learning-related changes in the brain, even after the stimulation has ended. The process by which tDCS induces learning-related changes remains to be fully understood, but existing evidence indicates that its mechanisms are similar to models of synaptic plasticity, as obtained from classical animal studies. Today, tDCS is being used to not only study how various types of skill learning occurs in the healthy adult brain, but also as a therapeutic means to help restore learningrelated processes, such as when the brain is met with injury (e.g., stroke) or as it is slowly degenerating (e.g., through natural aging). However, in order to fully realize the potential of tDCS, it is necessary that we fully understand the biological mechanisms that under-pin the learning-related neurophysiological mechanisms of tDCS. In this work, we combine the use of neuroimaging (fMRI and EEG) with brain stimulation (tDCS) in order to understand the relation between the key parameters of tDCS (such as current intensity and the stimulation polarity) and the resulting long-term neurophysiological changes in the brain (such as changes in the brain's blood flow or changes in the brain's rhythmic neural activity). Once we have an understanding of the nature of the relationship between stimulation settings and neurobiological changes, we can be closer to having "optimized" stimulation protocols which can lead to greater efficiency in clinical applications. In the latter part of this work, we examine how tDCS specifically affects learning of complex skills by applying stimulation while two groups of young (age 18-30 y) and older (65-77 y) adults are asked to learn difficult bimanual movements. Our positive findings show that tDCS is nicely suited in its ability to boost learning of difficult motor skills in both young and older adults, which are accompanied by lasting changes in the brain's functional neural network. This work opens the door for further research into how tDCS may be a powerful method for inducing longlasting neuroplastic changes in both healthy and patient (neurologic and psychiatric) human populations.