Neural Correlates of Positive and Negative Valence System Dysfunction in Adolescents Revealed by Data-Driven Parcellation and Resting-State Network Modeling

Abstract

Objective: Adolescence is a period of rapid brain development when symptoms of mood, anxiety, and other disorders often first emerge, suggesting disruptions in maturing reward circuitry may play a role in mental illness onset. Here, we characterized associations between resting-state network properties and psychiatric symptomatology in medication-free adolescents with a wide range of symptom severity.Methods: Adolescents (age 12-20) with mood and/or anxiety symptoms (n=68) and healthy controls (n=19) completed diagnostic interviews, depression/anhedonia/anxiety questionnaires, and 3T resting-state fMRI (10min/2.3mm/TR=1s). Data were preprocessed (HCP Pipelines), aligned (MSMAll), and parcellated into 750 nodes encompassing the entire cortex/subcortex (Cole-Anticevic Brain-wide Network Partition). Weighted graph theoretical metrics (Strength Centrality=CStr; Eigenvector Centrality=CEig; Local Efficiency=ELoc) were estimated within Whole Brain and task-derived Reward Anticipation/Attainment/Prediction Error networks. Associations with clinical status and symptoms were assessed non-parametrically (two-tailed pFWE<0.05).Results: Relative to controls, clinical adolescents had increased ventral striatum CEig within the Reward Attainment network. Across subjects, depression correlated with subgenual cingulate CStr and ELoc, anhedonia correlated with ventromedial prefrontal CStr and lateral amygdala ELoc, and anxiety negatively correlated with parietal operculum CEig and medial amygdala ELoc within the Whole Brain network.Conclusions: Using a data-driven analysis approach, high-quality parcellation, and clinically diverse adolescent cohort, we found that symptoms within positive and negative valence system constructs differentially associated with resting-state network abnormalities: depression and anhedonia, as well as clinical status, involved greater influence and communication efficiency in prefrontal and limbic reward areas, whereas anxiety was linked to reduced influence/efficiency in amygdala and cortical regions involved in stimulus monitoring.

Brain Connectomics and Severity of Internalizing Symptoms in Early Adolescence Predict Severity of Suicidal Ideation in Later Adolescence

“…For instance, in individuals with treatment resistant depression, there was no evidence of an association between regional glucose metabolism of the sgCG and SI (Ballard et al, 2015); however, other studies have found that inflammation in this region is higher in individuals with SI compared to those without SI (Holmes et al, 2018). In a recent study examining graph metrics in depressed adolescents, certain organizational properties other than eigenvector centrality of the right sgCG were associated with depression severity (Gabbay et al, 2020). However, we did not find this region as part of the model predicting increased internalizing severity in our sample.…”