Understanding Neuroplastic Effects of Transcranial Direct Current Stimulation through Analysis of Dynamics of Large-Scale Brain Networks

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Intrinsic adult neuroplasticity plays a critical role in learning and memory as well as mediating functional recovery from brain lesions like stroke and traumatic brain injuries. Extrinsic strategies to aid favorable modulation of neuroplasticity act as important adjunctive tools of neurorehabilitation. Transcranial direct current stimulation (tDCS) is an example of a non-invasive technique that can successfully induce neuroplastic changes in the human brain, although the underlying mechanisms are not completely understood. In this regard, characterization of neuroplastic changes in large-scale brain networks is a functional and necessary step towards non-invasively understanding neuroplastic modulation mediated by tDCS in humans. This dissertation, thus, aimed to understand the effects of tDCS, on large-scale brain network dynamics recorded through magnetoencephalography (MEG) through three specific aims that will provide novel insights into the mechanism(s) through which plastic changes are promoted by tDCS, specifically in the context motor learning. This dissertation pursued a systematic investigation of these changes in whole-head cortical dynamics using both model-free and model-based analysis techniques. Two experiments were conducted to dissociate between network changes mediated by tDCS at rest as well as when coupled with a task in order to determine optimal conditions for using tDCS for clinical purposes. Results from Study 1 using model-free analysis showed that a specific fronto-parietal network at rest was modulated up to a period of 30 minutes outlasting the duration of the stimulation. Further model-based analysis of this fronto-parietal network showed that these differences were driven by network activity primarily involving high frequency gamma band connectivity to and from the supplementary motor area to associated regions (left primary motor cortex (stimulated region), left prefrontal and parietal cortices). Results from Study 2 showed that the tDCS exerts highly polarity-specific effects on the impact of oscillatory network connectivity, within the functionally relevant fronto-parietal network, on behavioral changes associated with motor learning. These results advance our understanding of neuroplasticity mediated by tDCS and thus, have implications in the clinical use of tDCS for enhancing efficacy of neurorehabilitation in patients with stroke and traumatic brain injury.