Temporal interference methods for non-invasive deep brain stimulation

Project summary/abstract (30 lines max) A number of clinical disorders such as addiction, OCD, and schizophrenia, as well as neurological disorders including Parkinson’s disease, depend critically on deeper brain regions. Invasive deep brain stimulation of the nucleus accumbens, for example, has been shown to cause rapid, effortless loss of addiction, but these interventions are impractical due to the risks and costs of brain surgery. There is currently no developed non- invasive method of deep brain stimulation -- existing methods such as TMS, tDCS, tACS, and tFUS do not stimulate deep brain regions without also stimulating the overlying cortex, causing unwanted side effects and confounds. Moreover, there is unresolved debate about the causal role of deeper brain regions in cognition, as methods like fMRI show correlations but not causation between brain activity and behavior. This project explores temporal interference (TI) electrical neurostimulation as a potential new technology to test causal hypotheses about deep brain function in human cognition, which may further provide a foundation for treating clinical disorders involving deeper brain regions. TI works by applying two or more high frequency alternating current fields of slightly different frequencies. The fields individually do not stimulate brain activity, but where the fields overlap, there is a pattern of temporal interference which can activate neurons. Using combined TI and fMRI in human subjects, we will characterize the effect of TI on BOLD signals and functional connectivity, and how those vary with different TI frequencies and targeted brain regions (Aim 1). Then we will apply TI to the dorsal anterior cingulate cortex (dACC), to resolve longstanding debates about the causal role of dACC in cognition, especially in conflict monitoring, risk avoidance, and foraging behavior (Aim 2). The results will establish TI as a means of safely and effectively manipulating deep brain activity without activating the overlying cortical regions. This in turn will provide a new method for answering questions about the causal role of various deeper brain regions in cognition as well as a new means of treating clinical disorders involving deeper brain regions.