Targeted repair of neural pathways with focused ultrasonic waves

Weak or damaged neural pathways have been associated with many disabling neurological and mental conditions, including stroke, neurodegenerative disorders, and mental disorders such as depression. This project, led by researchers at the University of Utah, will use focused ultrasound, delivered through the cranium, for effective neurorehabilitation. The system and approach will enable operators to modulate the connection between any two regions of the human brain, and thus repair neural pathways that have been damaged or weakened. To maximize the impact of the therapies, the team will use seminars and demonstrations to engage human populations in Utah that have traditionally had limited access to cutting-edge neurological treatments. The feedback gathered from these groups will inform the design of the final therapeutic tools, optimizing the usability of the system for all persons regardless of socioeconomic status. There is currently no tool that would enable the noninvasive repair of neural networks in a targeted manner. Transcranial, focused ultrasound has the potential to provide such a tool, but there is no system and no approach for the modulation of neural connectivity. The project team, which consists of an engineer, a psychiatrist, and a magnetic resonance imaging (MRI) scientist, has designed a prototype device that can deliver effective and safe levels of neuromodulatory ultrasound into deep brain targets in humans. This project will develop the prototype into a system that can stimulate two nodes of a neural network simultaneously (Aim 1), thus promoting Hebbian plasticity under an appropriate stimulation-timing protocol (Aim 2). The team will apply this dual stimulation protocol to two key nodes within the cingulate cortex in humans, and quantify the resulting changes in connectivity using functional MRI (fMRI) blood-oxygenation-level-dependent activity (BOLD) and diffusion tractography. Successful completion of the project will result in a tool for the noninvasive repair of neural circuits with the potential to enable many affected individuals to return to work and normal life. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.