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Can we fix the brain like we fix electronic circuits?

Neurological and psychiatric disorders are dramatically increasing in prevalence due to aging population and social isolation. However, to date, there is no cure for any of the brain disorders. The goal of brain disorder treatments is to restore the brain’s function. Therefore, a key challenge is to quantify the brain function underlying behavior. Once the brain function algorithms underlying behaviors of interest can be quantitatively defined, minimizing the normal and diseased brain function difference can be defined as the objective function for the brain disorder treatment. The variables then can be optimized to minimize the objective function. In order to quantify the brain function algorithms underlying behavior, cell type specific whole brain function measurements are necessary. We utilize optogenetics combined with fMRI (ofMRI) to enable such measurements. Through computational modeling of ofMRI data, the functional interactions among different regions of the brain was then quantified. In combination with electrophysiological measurements, we further model brain function at a cellular level. In order to further understand the circuit, pathology relationship, we also utilize brain clearing methods to longitudinally quantify and model pathology. Through these efforts, we aim to enable systematic design of therapeutic interventions necessary for the treatment of brain disorders.