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A transdiagnostic data-driven study of children’s behaviour and the functional connectome

ABSTRACT: Behavioural difficulties are seen as hallmarks of many neurodevelopmental conditions. Differences in functional brain organisation have been observed in these conditions, but little is known about how they are related to a child’s profile of behavioural difficulties. We investigated whether behavioural difficulties are associated with how the brain is functionally organised in an intentionally heterogeneous and transdiagnostic sample of 957 children aged 5–15. We used consensus community detection to derive data-driven profiles of behavioural difficulties and constructed functional connectomes from a subset of 238 children with resting-state functional Magnetic Resonance Imaging (fMRI) data. We identified three distinct profiles of behaviour that were characterised by principal difficulties with hot executive function, cool executive function, and learning. Global organisation of the functional connectome did not differ between the groups, but multivariate patterns of connectivity at the level of Intrinsic Connectivity Networks (ICNs), nodes, and hubs significantly predicted group membership in held-out data. Fronto-parietal connector hubs were under-connected in all groups relative to a comparison sample and children with hot vs cool executive function difficulties were distinguished by connectivity in ICNs associated with cognitive control, emotion processing, and social cognition. This demonstrates both general and specific neurodevelopmental risk factors in the functional connectome. Highlights • We derived 3 behavioural profiles in 799 neurodevelopmentally at-risk children.• Namely, difficulties in hot executive function (EF), cool EF, and learning.• Global organisational properties of the functional connectome did not differ.• Connector hubs were more globally integrated in controls than at-risk groups.• Hot and cool EF groups differed in regional and network connectivity.

SUBMITTER: Jones J

PROVIDER: S-EPMC8551598 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Clinical assessments often fail to discriminate between unipolar and bipolar depression and identify individuals who will develop future (hypo)manic episodes. To address this challenge, we developed a brain-based graph-theoretical predictive model (GPM) to prospectively map symptoms of anhedonia, impulsivity, and (hypo)mania. Individuals seeking treatment for mood disorders (n = 80) underwent an fMRI scan, including (i) resting-state and (ii) a reinforcement-learning (RL) task. Symptoms were assessed at baseline as well as at 3- and 6-month follow-ups. A whole-brain functional connectome was computed for each fMRI task, and the GPM was applied for symptom prediction using cross-validation. Prediction performance was evaluated by comparing the GPM's mean square error (MSE) to that of a corresponding null model. In addition, the GPM was compared to the connectome-based predictive modeling (CPM). Cross-sectionally, the GPM predicted anhedonia from the global efficiency (a graph theory metric that quantifies information transfer across the connectome) during the RL task, and impulsivity from the centrality (a metric that captures the importance of a region for information spread) of the left anterior cingulate cortex during resting-state. At 6-month follow-up, the GPM predicted (hypo)manic symptoms from the local efficiency of the left nucleus accumbens during the RL task and anhedonia from the centrality of the left caudate during resting-state. Notably, the GPM outperformed the CPM, and GPM derived from individuals with unipolar disorders predicted anhedonia and impulsivity symptoms for individuals with bipolar disorders, highlighting transdiagnostic generalization. Taken together, across DSM mood diagnoses, efficiency and centrality of the reward circuit predicted symptoms of anhedonia, impulsivity, and (hypo)mania, cross-sectionally and prospectively. The GPM is an innovative modeling approach that may ultimately inform clinical prediction at the individual level. ClinicalTrials.gov identifier: NCT01976975.

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A transdiagnostic data-driven study of children’s behaviour and the functional connectome

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