Integrative Neuroscience. (360G-Wellcome-096521_Z_11_Z)

Please provide a summary of your proposed research, including key goals (no more than 200 words) The close relationship between neuronal activity and subsequent changes in vessel tone, thus cerebral blood flow, is termed neurovascular coupling (NVC). This coupling mechanism is not yet fully understood. In Multiple Sclerosis (MS), a chronic autoimmune inflammatory disease, hypoperfusion and impaired cerebrovascular reactivity are seen, both components of NVC. Our primary aim is to examine the effect of inflammation on NVC and how decoupling may contribute to tissue damage. MS individuals will be compared with matched controls, and blood biomarkers relating to vascular function will be measured. Another aim is to advance methodologies measuring NVC, studied previously at CUBRIC. In response to a visual task, gamma oscillations using MEG (magnetoencephalography) were regressed against BOLD/ASL (Blood Oxygen Level Dependent contrast/Arterial Spin Labelling) responses, measuring neuronal activity and blood flow, respectively. Regression coefficients define an empirical measure of NVC, with good repeatability. This project will optimise a motor task with these methods, assessing NVC in another functional domain relevant to MS. Many neuroimaging techniques are based on NVC; an increased knowledge of NVC pathways will provide insight into their signals. This research will deepen understanding of the role of NVC in brain pathologies, particularly MS, and potentially inform therapeutic directions.