CRCNS US-Israel Research Proposal: Multiscale analysis of brain-wide neuromodulation

Vanderbilt University, Nashville TN

Investigators

Abstract

Ongoing changes in motivation, mood, and alertness, play an important role in healthy brain function, and are disrupted in neurological and psychiatric disorders. The project will analyze neural circuitry that underpins these changes across behavioral states. It will do so by developing a new computational analysis method, validating this method on recordings of zebrafish brain activity, and using this method to analyze human brain activity. The project will also develop an online educational workshop on extraction of knowledge from big neural data. The workshop will provide a hands-on approach to analysis and modeling of large neuroscience datasets — from simulations to zebrafish to humans — and in this way will help train a new generation of computational neuroscientists. The project proposes a new computational framework for statistical inference of neuromodulation in functional imaging data across species and scales. It will validate and deploy this framework in three steps. First, it will validate this framework in simulations of neuronal network activity with known ground truth. Second, it will deploy this framework to zebrafish brain-wide cell-resolution calcium imaging data. This deployment will enable the discovery of neuromodulatory systems, and the benchmarking of these discoveries against existing anatomical knowledge. Third, it will translate this framework to analysis of human functional MRI data. This translation will facilitate noninvasive inference of neuromodulation in living humans across brain states. Collectively, completion of these steps will deliver an integrative statistical framework for inferring brain-wide neuromodulatory systems across species and spatial scales. In the short term, this completion will provide investigators with new ways to infer effects of neuromodulation from non-invasive imaging. In the long term, this completion will help facilitate detection of dysregulated neuromodulation across brain states. Collectively, these deliverables will accelerate discovery of foundational aspects of brain activity and function. This project is funded jointly by the Neural Systems Cluster in the Biological Sciences Directorate and the Division of Information and Intelligent Systems in the Computer and information Science and Engineering Directorate. A companion project is being funded by the US-Israel Binational Science Foundation (BSF). 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.