Project Summary (Abstract) Transcranial electrical stimulation (tES) represents a promising, noninvasive methodology by which to test causal mechanisms of human cognitive brain functions, and to translate systems neuroscience theory into therapy. This proposal utilizes whole-brain individualized neural modeling to better understand and harness the causal mechanisms by which tES modulates brain activity dynamics and cognitive functioning. The proposed research addresses key limitations of previous tES cognitive-enhancement studies, including uncertain mechanisms, efficacy, and individual variability, by drawing on an explicit neurocomputational architecture from which to derive strong brain-behavior linkages. In particular, a primary strength of the proposed project is its utilization of the Mesoscopic Individualized Neurodynamic (MINDy) modeling approach and platform previously developed and validated by the investigative team. The proposed project provides an ambitious extension of our prior work, by fully leveraging the MINDy platform to validate and test an innovative neural control engineering approach for analyzing, predicting, and manipulating causal relationships between large-scale brain networks (salience [SAL], frontoparietal control [FPN], default mode [DMN]) and their influence on cognitive function. We build individualized MINDy models for each participant based on their resting-state electroencephalographic (EEG) data, then further optimize model estimation through a novel closed-loop tES+EEG stimulation protocol (Aim 1). We then apply MINDy to modulate brain network dynamics associated with attention and cognitive control, drawing upon the influential triple-network model, by optimally stimulating the SAL network in a model-guided manner to shift from a DMN-dominant to FPN-dominant mode, under resting-state EEG conditions (Aim 2). Finally, we extend the stimulation protocol to cognitive task contexts (Aim 3), by implementing model-guided shifts of FPN-DMN balance as participants perform a well-established experimental paradigm probing attention and cognitive control (AX-CPT), testing for performance enhancements in terms of theoretically-interpretable behavioral markers. The findings of this project will have high

Project Narrative (Relevance) This project will provide critical and detailed information regarding the brain basis of human higher cognitive functioning, such as the control of attention, and whether such functioning can be enhanced through brain electrical stimulation techniques that are low-cost, non-invasive, and safe. This information has high relevance for public health, in that it will be used to identify key neural and behavioral markers that can be used as targets in future intervention efforts directed towards individuals with mental health disorders associated with cognitive impairment (e.g., schizophrenia, dementia, autism).