[R01] Volatility and rigidity in brain states: A novel approach for understanding andpredicting youth externalizing behaviors
Ente: National Institute of Mental Health
Scadenza: 2031-04-30
Importo max: 620.848 EUR
Paese: US
Descrizione
Project Summary
Externalizing behaviors, marked by weakened impulse control and heightened sensation seeking, are
pervasive across various neurodevelopmental and psychiatric disorders. The progression of these behaviors
varies widely between individuals, fluctuating over time, and profoundly predictive of academic and social
functioning. Understanding the neurodevelopmental factors that influence the longitudinal changes in
externalizing behaviors is critical for public health. Clinical research has traditionally focused on averaged
regional brain responses and functional connectivity across trials, often overlooking the complexity of brain
dynamics. Emerging neuroimaging findings underscore that cognitive function depends not only on the brain's
ability to maintain stable, task-relevant brain states (stability) but also on its capacity to disengage efficiently
from non-optimal states (flexibility). We propose a novel neural dynamic model that captures the volatility
and rigidity of state-dependent brain dynamics in relation to externalizing behaviors. In this context,
volatility refers to the brain's difficulty in sustaining a stable, optimal state during cognitive tasks, while rigidity
refers to the brain's inertia to disengage from an obsolete state when task demands shift. By leveraging the
large-scale, longitudinal Adolescent Brain Cognitive Development (ABCD) dataset and employing cutting-
edge single-trial and state-space models, we aim to characterize the volatility and rigidity of neural circuit
dynamics during cognitive tasks in children, their developmental trajectories, and sex differences. Our primary
focus will be on the cognitive control and reward systems where dysfunctions have been linked to externalizing
symptoms. Our approach aligns with the Research Domain Criteria (RDoC) framework and aims to offer
unprecedented insights into the neurodevelopmental mechanisms underlying externalizing behaviors.
Specifically, we will (1) examine volatility of task-dependent brain representation and rigidity of brain state
dynamics during cognitive control and reward processing, (2) investigate the associations between these
neural dynamics and key components of externalizing symptoms, such as impulsivity and reward
responsiveness, (3) trace developmental trajectories of these neural dynamics and their relationship with
longitudinal changes in externalizing behaviors, (4) develop predictive models within the RDoC framework to
forecast externalizing symptoms and their progression over time, (5) characterize neurodevelopmental
mechanisms that contribute to sex-specific externalizing behaviors, (6) uncover heterogeneous patterns of
longitudinal changes of externalizing behavior and the underlying neural dynamics, and (7) test reproducibility
and generalizability of our findings using large independent cross-sectional and longitudinal datasets. These
endeavors will deepen our understanding of the neurocognitive factors contributing to longitudinal
Istituzione: STANFORD UNIVERSITY
PI: Weidong Cai
Progetto: 1R01MH140868-01A1
Settori: National Institute of Mental Health
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