Studies using transcranial direct current stimulation (tDCS) to enhance motor training areoften irreproducible. This may be partly due to differences in stimulation parameters across studies, but it is also plausible that uncontrolled placebo effects may interact with the true ‘treatment’ effect of tDCS. Thus, the purpose of this study was to test whether there was a placebo effect of tDCS on motor training and to identify possible mechanisms of such an effect. Fifty-one participants (age: 22.2 ± 4.16; 26 F) were randomly assigned to one of three groups: active anodal tDCS (n=18), sham tDCS (n=18), or no stimulation control (n=15). Participant expectations about how much tDCS could enhance motor function and their general suggestibility were assessed. Participants then completed 30 trials of functional upper extremity motor training with or without online tDCS. Stimulation (20-min, 2mA) was applied to the right primary motor cortex (C4) in a double-blind, sham-controlled fashion, while the control group was unblinded and not exposed to any stimulation. Following motor training, expectations about how much tDCS could enhance motor function were assessed again for participants in the sham and active tDCS groups only. Results showed no effect of active tDCS on motor training (p=.67). However, there was a significant placebo effect, such that the collapsed sham and active tDCS groups improved more during motor training than the control group (p=.02). This placebo effect was significantly influenced by post-training expectations about tDCS (p=.0004). Thus, this exploratory study showed that there is a measurable placebo effect of tDCS on motor training, likely driven by participants’ perceptions of whether they received stimulation. Future studies should consider placebo effects of tDCS and identify their underlying mechanisms in order to leverage them in clinical care.

Repetitive practice of functional movement patterns during motor rehabilitation are known to drive learning (or relearning) of novel motor skills, but the learning process is highly variable between individuals such that responsiveness to task-specific training is often patient-specific. A number of neuroimaging and neurophysiological methods have been proposed to better predict a patient’s responsiveness to a given type or dose of motor therapy. However, these methods are often time- and resource-intensive, and yield results that are not readily interpretable by clinicians. In contrast, standardized visuospatial tests may offer a more feasible solution. The work presented in this dissertation demonstrate that a clinical paper-and-pencil test of visuospatial function may improve predictive models of motor skill learning in older adults and individuals with stroke pathology. To further our understanding of the neuroanatomical correlates underlying this behavioral relationship, I collected diffusion-weighted magnetic resonance images from 19 nondemented older adults to determine if diffusion characteristics of white matter tracts explain shared variance in delayed visuospatial memory test scores and motor skill learning. Consistent with previous work, results indicated that the structural integrity of regions with the bilateral anterior thalamic radiations, corticospinal tracts, and superior longitudinal fasciculi are related to delayed visuospatial memory performance and one-week skill retention. Overall, results of this dissertation suggest that incorporating a clinical paper-and-pencil test of delayed visuospatial memory may prognose motor rehabilitation outcomes and support that personalized variables should be considered in standards of care. Moreover, regions within specific white matter tracts may underlie this behavioral relationship and future work should investigate these regions as potential targets for therapeutic intervention.

Motor skill learning is important to rehabilitation, sports, and many occupations. When attempting to learn or adapt a motor skill, some individuals learn slower or less compared to others despite the same amount of motor practice. This dissertation aims to understand the factors that contributed to such variability in motor learning, and thereby identify viable methods to enhance motor learning. Behavioral evidence from our lab showed that visuospatial ability is positively related to the extent of motor learning. Neuroimaging studies suggest that motor learning and visuospatial processes share common frontoparietal neural structures, and that this visuospatial-motor relationship may be more pronounced in the right hemisphere compared to the left. Thus, the overall objective of this dissertation is to determine if aspects of motor learning (such as the rate and extent of skill acquisition) may be modifiable through neuromodulation of the right frontoparietal network. In Aim 1, anodal transcranial direct current stimulation (tDCS) was used to test whether modulating the right parietal area affects visuospatial ability and motor skill acquisition. A randomized, three-arm design was used, which added a no-tDCS control group to the double-blinded sham-control protocol to address placebo effects. No tDCS treatment effect was observed, likely due to low statistical power to detect any treatment effects as the study is still ongoing. However, the current results revealed a unique finding that the placebo effect of tDCS was stronger than its treatment effect on motor learning, with implications that tDCS and motor studies should measure and control for placebo effects. In Aim 2, right frontoparietal connectivity during resting-state EEG was estimated via alpha band imaginary coherence to test whether it correlated with visuospatial performance and motor skill acquisition. As a preliminary step towards leveraging the frontoparietal network for EEG-neurofeedback applications, this work found that alpha imaginary coherence was positively correlated with visuospatial function, but not with motor skill acquisition during a limited dose of motor practice (only 5 trials). This work establishes a premise for developing frontoparietal alpha IC-based neurofeedback for cognitive training in rehabilitation, while warranting future studies to test the relationship between alpha IC and motor learning with a more extensive motor training regimen.