Brain-behavior Prediction

Multivariate neural predictors of behavioral and clinical outcomes in youth

Previous research has revealed that connectivity patterns in youth are linked to behavior, cognition, and psychopathology. However, identifying robust brain-behavior relationships requires large sample sizes, and sophisticated analysis techniques (such as appropriate cross-validation and multivariate methods that can capture complex, distributed brain patterns) to pick up on small effect sizes, while ensuring generalizability to other samples. The ABCD Study is an ideal dataset to answer questions testing the relationship between connectivity and cognition in adolescence due to its large sample size of over 11,000 adolescents, and extensive battery of neural, behavioral, and health-related data. This line of work utilizes the large ABCD samples, alongside other large samples such as HCP, to demonstrate the close relationship between the connectome and a wide range of interconnected outcomes such as cognition, sleep, and psychopathology (Molloy et al., 2025; Molloy et al., 2026; Michael et al., 2025).

References

2026

Decreased sleep is linked longitudinally and directionally to alterations in the brain’s intrinsic functional architecture

M. Fiona Molloy, Aman Taxali, Mike Angstadt, Katherine Toda-Thorne, Katherine L. McCurry, Alexander Weigard, Omid Kardan, Camille Lehrmann, Joshua Vens, Cleanthis Michael, Mary M. Heitzeg, and Chandra Sripada

Developmental Cognitive Neuroscience, Apr 2026

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Previous cross-sectional studies demonstrated that reduced sleep is associated with widespread changes in the brain’s intrinsic functional architecture. The present study extends this work by clarifying links between sleep and the developing brain during adolescence both longitudinally (across two years) and directionally (does reduced sleep cause connectivity changes or are connectivity changes the cause of reduced sleep?). Our novel approach combines the Adolescent Brain Cognitive Development (ABCD) Study, a longitudinal observational study of 11,878 youth, and a second sample of 76 adult participants scanned after a typical night of sleep and after a sleep deprivation causal manipulation. First, in the ABCD dataset, we identified a robust and generalizable neurosignature of reduced sleep. Second, in an independent sample of ABCD participants, we demonstrate that greater reductions in sleep duration across two years are significantly related to greater expression of this neurosignature. Third, in the sleep deprivation dataset, we show that expression of the ABCD reduced sleep neurosignature is significantly increased within individuals following sleep deprivation, and that neurosignatures of reduced sleep from the two samples exhibit significant spatial correspondence. These results clarify links between sleep and the developing brain and provide novel evidence that changes in sleep produce characteristic brain functional connectivity changes across adolescence.

2025

Regional, but not brain-wide, graph theoretic measures are robustly and reproducibly linked to general cognitive ability

M Fiona Molloy, Aman Taxali, Mike Angstadt, Tristan Greathouse, Katherine Toda-Thorne, Katherine L McCurry, Alexander Weigard, Omid Kardan, Lily Burchell, Maria Dziubinski, Jason Choi, Melanie Vandersluis, Cleanthis Michael, Mary M Heitzeg, and Chandra Sripada

Cerebral Cortex, Apr 2025

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General cognitive ability (GCA), also called “general intelligence,” is thought to depend on network properties of the brain, which can be quantified through graph theoretic measures such as small worldness and module degree. An extensive set of studies examined links between GCA and graphical properties of resting state connectomes. However, these studies often involved small samples, applied just a few graph theory measures in each study, and yielded inconsistent results, making it challenging to identify the architectural underpinnings of GCA. Here, we address these limitations by systematically investigating univariate and multivariate relationships between GCA and 17 whole-brain and node-level graph theory measures in individuals from the Adolescent Brain Cognitive Development Study (n = 5937). We demonstrate that whole-brain graph theory measures, including small worldness and global efficiency, fail to exhibit meaningful relationships with GCA. In contrast, multiple node-level graphical measures, especially module degree (within-network connectivity), exhibit strong associations with GCA. We establish the robustness of these results by replicating them in a second large sample, the Human Connectome Project (n = 847), and across a variety of modeling choices. This study provides the most comprehensive and definitive account to date of complex interrelationships between GCA and graphical properties of the brain’s intrinsic functional architecture.
Somatomotor disconnection links sleep duration with socioeconomic context, screen time, cognition, and psychopathology

Cleanthis Michael, Aman Taxali, Mike Angstadt, Katherine L. McCurry, Alexander Weigard, Omid Kardan, M. Fiona Molloy, Katherine Toda-Thorne, Lily Burchell, Maria Dziubinski, Jason Choi, Melanie Vandersluis, Luke W. Hyde, Mary M. Heitzeg, and Chandra Sripada

Biological Psychiatry Global Open Science, Apr 2025

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Background Sleep is critical for healthy brain development and emotional wellbeing, especially during adolescence when sleep, behavior, and neurobiology are rapidly evolving. Theoretical reviews and empirical research have historically focused on how sleep influences mental health through its impact on higher-order brain systems. No studies have leveraged data-driven network neuroscience methods to uncover interpretable, brain-wide signatures of sleep duration in adolescence, their socio-environmental origins, and their consequences for cognition and psychopathology. Methods We implement graph theory and component-based predictive modeling to examine how a multimodal index of sleep duration (parent-report, youth-report, Fitbit) is associated with intrinsic brain architecture in 3,037 youth (11-12 years) from the Adolescent Brain Cognitive DevelopmentSM Study. Results We demonstrate that network integration/segregation exhibit a strong, generalizable multivariate association with sleep duration (r=.23, p\textless.001). The multivariate signature of shorter sleep predominantly involved increasing disconnection of a lower-order system, the somatomotor network, from other systems. We next identify a single component of brain architecture as the dominant contributor of this relationship (r=.15), which again exhibited this somatomotor disconnection motif. Finally, greater somatomotor disconnection is associated with lower socioeconomic resources, longer screen times, reduced cognitive/academic performance, and elevated externalizing problems (β’s\textgreater0.03, p’s≤.007). Conclusions These findings reveal a novel neural signature of shorter sleep in adolescence that is intertwined with environmental risk, cognition, and psychopathology. By robustly elucidating the key involvement of an understudied brain system in sleep, this study can inform theoretical and translational research directions on sleep to promote neurobehavioral development and mental health during the adolescent transition.