Investigating human motor learning using multimodal imaging and brain stimulation

Many post-stroke motor rehabilitation programmes are developed from methods used to augment and improve motor skill learning in healthy controls. An important step towards developing effective motor rehabilitation strategies is therefore understanding the neurophysiology of healthy motor learning, and then assessing if (and if so, how) this changes after a stroke. This thesis contains work using multimodal methods to further understanding of the neurophysiological underpinning of motor skill learning in both healthy controls and stroke survivors. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) are used to measure brain activity and neurotransmitter concentrations, while transcranial direct current stimulation (tDCS) is used to modulate both brain activity and motor learning performance. The first experiment, in Chapter Three, uses ultra-high field MRS to investigate healthy motor learning, and observed a reduction in GABA concentration which is specific to performance of a learning task. This finding replicates previous literature, and provides support of the important role of inhibition in normal motor learning. In the following two Chapters, the role of the ipsilateral motor cortex is investigated in tDCS-influenced healthy motor learning. Following stroke, the ipsilateral (or contralesional) motor cortex has been shown to increase involvement in movement, but it’s role is less well established. Here, cathodal tDCS to the task-dominant (left) hemisphere in healthy controls is combined with fMRI (Chapter Four) or bilateral TMS (Chapter Five). In Chapter Four, offline cathodal tDCS prior to task performance resulted in increased ipsilateral motor cortex activity during motor task performance. In Chapter Five, the same tDCS stimulation paradigm did not find group-wide cortical excitability changes, however relationships were observed at the individual subject level between behaviour and TMS measures (baseline response time predicts left hemisphere cortical excitability change, and rate of learning correlates with right hemisphere facilitation change). These relationships may provide insight into the neurophysiological changes caused by cathodal tDCS and how these may relate to behaviour. The final experimental chapter focuses on identification of differences in learning ability between healthy controls and stroke survivors, and presents a successful proof-of-principle study introducing a novel motor task which could be used to assess this intergroup difference. This task has been developed to overcome limitations of existing tasks which require volitional movement, and often dexterity, to perform. Taken together, these studies strengthen our knowledge of the key role of inhibition in healthy motor learning, highlight the importance of understanding the contralesional hemisphere following stroke, and introduce a novel task which could be developed further to investigate potential differences between motor skill learning in healthy controls and stroke survivors.

Keywords: Motor learning
GABA
Magnetic Resonance Spectroscopy
Magnetic Resonance Imaging
Stroke
Brain stimulation
Advisor: Fleming, M
Stagg, C