Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?

Abstract

Introduction: High 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.

Methods: A 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.

Results: Relevance 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.

Conclusions: The combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.

Fig 1. Illustration of a pattern regression model with hypothetical 2D data.

The numbers in the squares correspond to activation levels in different brain voxels. Each brain scan corresponds to a point in a 2D voxel space. The goal is to “train” a predictive function that given a new brain scan can accurately decode the correspondent clinical score.

Fig 2. Maps for decoding PGBI-10M at screen based on patterns of activation to win blocks using a leave-one-out cross-validation framework.

A: Voxel-based predictive pattern. The colour bar indicates the weight of the voxels for decoding the clinical score. B: Region-based pattern localization map computed from the voxel based predictive pattern displayed in Fig 2A. The colour bar indicates the percentage of the total normalized weights that each anatomically labelled region explains.