Precise mapping of human brain function and connectivity for diseases of neurological network disruption

Neurological diseases and neuropsychiatric conditions constitute a looming crisis for ageing societies, including the UK. Many of these diseases involve pathological alterations to deep brain “nuclei”, which cascades into disruption of larger brain networks. Magnetic resonance imaging (MRI) is a promising technology for studying, monitoring, and developing therapeutics for these diseases. Specifically, we can measure brain activity with functional MRI and structural connectivity with diffusion MRI. However, current functional and diffusion MRI methods are limited in spatial resolution (>1mm) and cannot precisely measure early changes in many small nuclei and their associated networks. The proposed research will develop novel functional and diffusion MRI technologies to map brain function and connectivity with unprecedented spatial precision and accuracy. The main goals are to: i. develop novel technologies to enable sub-0.5mm diffusion MRI for precise mapping of brain structural connectivity. ii. develop novel technologies to enable sub-0.5mm functional MRI for robust detection of brain activity. iii. apply the developed methods to improve the accuracy of targeting and response measurement for transcranial ultrasound stimulation. iv. translate prototype methods into robust tools and investigate future technical and clinical research directions. These new methods will enable previously unfeasible clinical and basic science research to be performed.