Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects

Abstract

The ability to induce cortical plasticity with non-invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours. Additionally, and importantly, the induction of lasting changes in cortical excitability can, under some conditions, reversibly modify behaviour and interact with normal learning. Such findings have driven a large number of recent studies examining whether by using such approaches it might be possible to induce functionally significant changes in patients with a large variety of neurological and psychiatric conditions including stroke, Parkinson's disease and depression. However, even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high. This variability at present limits the therapeutic usefulness of these techniques. The cause of this variability is multifactorial and to some degree still unknown. However, a number of factors that can influence the induction of plasticity have been identified. This review will summarise what is known about the causes of variability in healthy subjects and propose additional factors that are likely to be important determinants. A greater understanding of these determinants is critical for optimising the therapeutic applications of non-invasive brain stimulation techniques.

Figures

Figure 1. Schematic diagram demonstrating relative magnitude (y-axis) and potential significance (x-axis) of determinants on neuroplasticity induction by NBS with some examples indicated

Potential significance is a somewhat subjective estimation of the authors of the future potential of the various determinants to play a role in purposefully modulating direction and magnitude of NBS-induced plasticity. Zero (y-axis) represents the level of NBS-induced plasticity that would be expected in a random adult subject group. Colours of bars (see inserted legend) indicate the level of evidence from the number and consistency of the available studies. *Note that with one form of NBS (QPS), significantly larger priming effects have been reported in one study. Abbreviations: AG, agonist; ANT, antagonist; DA, dopamine; Ach, acetylcholine; NE, noradrenaline.