This proposal aims to improve brain functions by investigating key, complementary questions about the neural mechanisms of selective visual attention and value-based decision-making. Selective visual attention and value- based decision-making are highly interactive. Indeed, patients diagnosed with attention deficit hyperactivity disorder (ADHD), which affects ~5% of the children in the US, and schizophrenia, which affects ~1.1% of the US population, suffer not only from severe attentional deficits, but also from profound decision deficits1,2. Selective visual attention describes the process by which sensory information is filtered in favor of items that are behaviorally and contextually relevant 3. Value-based decision-making refers to the process by which a subject chooses from several alternatives based on the subjective values that were assigned to them4. Despite the importance of these two cognitive functions, however, we are still only at the beginning stages of understanding the neural circuits that underlie these two cognitive processes. Evidence to date points toward the engagement of neurons in prefrontal, parietal, and visual cortices in both value-based decision-making and selective visual attention3,4. However, it is currently debatable to what degree these two cognitive processes are interdependent, both at the behavioral and the neural circuit level. My long-term goal is a research career focused on investigating cortical circuits underlying these cognitive processes and applying this knowledge to improve brain functions in health and disease. Specifically, this proposal aims to investigate the neural circuitry and neural computations of the above two cognitive functions in non-human primates (NHPs), which are the closest homologs to humans, using state-of-the-art, high-density multi-electrode array (HDMEA) recordings in prefrontal and visual cortex (K99). In addition, I will investigate ways to enhance and modulate both cognitive functions using closed-loop neurofeedback based on HDMEA recordings in prefrontal cortex (K99 and R00), and through pharmaceutical perturbations of prefrontal dopaminergic activity (R00). The proposal aims at exploring largely uncharted territory and introduces several innovative experimental approaches and techniques including but not limited to 1) high density laminar multi-electrode array recordings to investigate large neuronal populations across cortical layers simultaneously in multiple brain areas, 2) computational approaches for single-trial analyses of large neuronal populations, 3) new effective and robust neurofeedback protocols, which will be crucial to identify and modulate signals that are causally linked to specific aspects of behavior and cognition (e.g. selective attention), in order to effectively and robustly enhance them. The central hypothesis is that the neural mechanisms of selective visual attention and value-based decision-making are heavily interdependent but dissociable. Pinpointing the specific neural circuits underlying both cognitive functions will lead to the development of techniques to effectively enhance both functions in health and disease.
/ Public Health Relevance Patients diagnosed with attention deficit hyperactivity disorder (ADHD), which affects ~5% of the children in the US, and schizophrenia, which affects ~1.1% of the US population, suffer not only from severe attentional deficits, but also from profound decision deficits. My research focuses on providing a deep, circuit-level understanding of the interaction between selective visual attention and value-based decision-making. By combining state-of-the- art neurophysiological approaches and causal methods, this research is expected to produce results that exert a large and sustained impact on our ability to improve brain function in health and disease, such as ADHD.