Modulating Human Cortical Plasticity via Transcranial Direct Current Stimulation: Basic & Clinical Applications

Abstract

As humans we have a unique ability to study, and even to modify the makeup of our own existence. The concept of changing oneself has always intrigued me, and it was what initially piqued my interest in the study of the human brain. In my estimation, the brain was where most of our “existence” derived from (I’ve changed my mind about that somewhat since then), and therefore learning about it, and how to modify it, would be quite an interesting undertaking. My passion for this topic led me to work with Dr. Kelvin Lim, who at the time was building momentum for studying the clinical potential of non-invasive neuromodulation. Over the course of 5 years working with Kelvin, I was able to learn a significant amount regarding neuromodulation, research and science as a whole. This dissertation describes two of my main projects. These studies focus on researching the basic and clinical applications of transcranial direct current stimulation (tDCS) as a means to modulate human brain plasticity. The first project, described in chapter II, was a basic science study which aimed to investigate how tDCS interacts with functional brain state. Previous literature has reported on the ability of tDCS to modulate plasticity, both in humans and in animal models. However, given the non-focal nature of tDCS, there is an open debate as to how specific outcomes (physiological or behavioral) are achieved. Recently, a hypothesis has been proposed that active brain networks or populations of neurons are preferentially susceptible to the influence of electric fields over inactive networks or groups of cells. This ‘activity-selectivity’ hypothesis has not been thoroughly tested in studies using physiological measures. In this study I use a novel electrophysiological paradigm to investigate the impact of tDCS on plasticity in the auditory cortex. The unique features of the paradigm allowed me to analyze stimulus specific effects of tDCS, making it possible to test the ‘activity-selectivity’ hypothesis using a novel physiological measure. The third chapter of the thesis describes a clinical trial where we used tDCS in combination with cognitive training to treat impaired executive functions in children with fetal alcohol spectrum disorders (FASD). Exposure to alcohol in the womb impairs neuroplasticity in the developing brain and often leads to severe cognitive deficits later in life. Cognitive training is one of a few treatment options for these deficits, however treatment times are long and difficult to complete. Research has shown that pairing cognitive training with tDCS enhances efficacy and can allow for a shorter intervention. However, tDCS has not been tried in children with FASD and it is not clear if it would be tolerated or efficacious in this population. With this in mind, we conducted a first of its kind clinical trial in children with FASD to test the tolerability and feasibility of tDCS augmented cognitive training and its effects on executive functioning. In sum, this dissertation describes two of my major studies which describe the characteristics and the use of tDCS in both a basic and clinical setting. I believe that the findings generated by these studies will make a significant and positive effect on the field of tDCS and its use in the clinic.