Studies on the neural representation of sequential movement order have provided insight into the organization of movement, but research on sequential movement timing has produced inconclusive results. In this proposal I will investigate the neural representation of timing in movement production. Based on previous findings I hypothesize that information about the sequential timing of movements is stored in the cerebellum and the ventral premotor cortex. To address this hypothesis, I will use comp limentary methods. Novel multivoxel pattern analyses of fMRI signals will reveal the distribution and spatial configuration of temporal encoding as opposed to the sequence of movements across brain regions and elucidate how these representations change with learning. Non-invasive cortical stimulation with healthy subjects and behavioural studies with cerebellar patients will probe the causal contribution of cortical and cerebellar encoding of temporal information. Finally, these studies will be complimented by behavioural tests with mice mutants and electrophysiology in wild-type mice to reveal how individual neurons and neural populations in the cerebellum encode sequential motor timing. Taken together, my integrated approach will identify the neural basis of accurate timing required for many of our everyday skilled movements. In our daily life, we effortlessly produce highly skilled movements: We coordinate our lips, vocal chords and tongue to utter a sentence, our arm and hand to throw a ball to a target and our fingers to play a melody on a piano. In addition to what muscles to move, knowing when to move is necessary to achieve the desired goal. However, how the nervous system acquires and stores representations of movement timing is unknown. I will combine neuroimaging in humans and neurophysiology in mice to addr ess this question. Advanced brain imaging in humans will reveal local patterns of neural activity across the brain that carry information about movement timing and elucidate how these activity patterns progressively change with learning. To test whether these local representations are indispensable for timing accuracy, I will temporarily and non-invasively interfere with these regions and assess whether patients with local brain degeneration are affected. Finally, neurophysiology in rodents will reveal how individual neurons and neuronal populations ensure accurate timing in a series of movements. My results will advance our knowledge of how motor timing is stored in the brain. I believe that, ultimately, this knowledge will improve the rehabilitation of individuals with movement coordination.

Vacation Scholarships 2019 - Bangor University

Damage to the peripheral nerves of the hand dramatically disrupts feeling and movement, and precipitates a variety of reorganisational changes in the brain. Preliminary evidence from our work with hand transplant and replant recipients suggests that such changes are maladaptive and limit recovery. Specifically, we find that passive cutaneous stimulation of the uninjured hand results in significant positive functional MRI (fMRI) activity in ipsilateral primary sensory cortex (S1), and moreover, the strength of this activity negatively correlates with sensory performance. Positive ipsilateral S1 activity during hand stimulation is not observed in healthy controls, and represents a marker of trauma-related interhemispheric reorganization. Building from these initial data, which are limited by few patient cases, the proposed research will investigate the clinical significance of nerve-trauma-related brain changes in the more numerous conditions of median/ulnar and digital nerve injury and repair. Using our established fMRI and behavioural methods, we expect to identify brain changes in patients that predict poor sensory performance of the injured hand. This research will significantly advance our understanding of the functional consequences of brain changes following nerve damage to the hand, and set the stage for the development of new rehabilitation therapies designed to help reverse these changes. When a nerve of the hand is cut, the signalling between the hand and brain is disrupted, and as a consequence, the brain changes. These injuries are extremely common, with significant and longstanding personal and societal costs. Better understanding the links between brain changes and functional recovery holds promise for improving patient outcomes, and reducing these costs. This is the purpose of the proposed research. We will investigate the clinical significance of nerve-trauma-related brain changes in patients who have undergone surgical repairs of the nerve(s) of the hand. Using our established functional MRI and behavioural methods, we expect to identify brain changes in patients that predict poor sensory performance of the injured hand. This research will significantly advance our understanding of the functional consequences of brain changes following nerve damage to the hand, and set the stage for the development of new rehabilitation therapies designed to help reverse these changes.