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Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5). Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18) from those with lower (n = 34) trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7). Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03) youth with different (higher vs lower) trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This approach has potential to identify patterns of neural markers of future clinical course.

IntroductionHigh comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points.MethodsA sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels.ResultsRelevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas.ConclusionsThe combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.