Impairments in cognitive systems that regulate the ability to adaptively engage with and respond to changing stimuli and goals are a hallmark of psychopathology. Identifying the underlying cognitive and neural factors that drive dysfunctional behavioral dynamics is a primary goal for psychiatric research. However conventional methods are unable to reveal latent constructs that govern these dynamic processes. Novel computational approaches are required to reveal latent behavioral dynamics and traits associated with psychopathology, and their neural circuit basis, within the Research Domain Criteria (RDoC) framework. Most, if not all, psychiatric disorders have a neurodevelopmental origin and are associated with atypical maturation of cognitive brain networks. Cognition is a dynamic process, which relies on flexible inhibitory control, goal-directed beliefs that impact moment-to-moment expectation, and the capacity to learn and adapt from prior decisions. Developing dynamic latent behavioral models of cognition is significant in the context of psychopathology, because deficits in inhibitory control, performance monitoring and belief updating are implicated in multiple psychiatric disorders including ADHD, autism, and schizophrenia. Our overarching goal is to develop and validate Hierarchical Latent Variable Dynamics (HLVD), a novel integrative computational approach for discovering robust latent behavioral constructs and their neural circuit bases. The proposed studies will leverage the longitudinal Adolescent Behavioral and Cognitive Development (ABCD) study, which has generated unprecedented amounts of ?Big Data? (N>5,000) for charting cognitive and brain development in children and adolescents over time. Crucially, HLVD will be used to identify and validate novel latent constructs of behavioral dynamics that are expected to be significant dimensional predictors of externalizing symptoms and developmental psychopathology. The proposed studies will significantly enhance our understanding of RDoC constructs and provide new insights into latent behavioral dynamics and traits associated with psychopathology in the developing brain. Our studies are highly relevant to the mission of the NIMH initiative RFA-MH-19-242, which seeks to accelerate research on neurodevelopment and trajectories of risk for mental illness. Our innovative approach will ultimately aid in the development of biomarkers for early detection and treatment of psychiatric disorders.

Public Health Relevance

Impairments in cognitive systems that regulate the ability to adaptively engage with and respond to changing stimuli and goals are a hallmark of psychopathology. Here, we propose to develop and validate integrative models for discovering robust latent behavioral constructs underlying cognition, their neural circuit bases, and relation to clinical symptoms using a novel computational Big-Data approach. The proposed studies will significantly enhance our understanding of the validity of NIMH Research Domain Criteria (RDoC) constructs, and contribute new insights into latent behavioral dynamics and traits associated with psychopathology in the developing brain. !

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH121069-01
Application #
9841689
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Pacheco, Jenni
Project Start
2019-07-26
Project End
2024-05-31
Budget Start
2019-07-26
Budget End
2020-05-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305