Brain age prediction using fMRI network coupling in youths and associations with psychiatric symptoms

OBJECTIVE: Magnetic resonance imaging (MRI) has shown that estimated brain age is deviant from chronological age in various common brain disorders. Brain age estimation could be useful for investigating patterns of brain maturation and integrity, aiding to elucidate brain mechanisms underlying these heterogeneous conditions. Here, we examined functional brain age in two large samples of children and adolescents and its relation to mental health. METHODS: We used resting-state fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC; n = 1126, age range 8–22 years) to estimate functional connectivity between brain networks, and utilized these as features for brain age prediction. We applied the prediction model to 1387 individuals (age range 8–22 years) in the Healthy Brain Network sample (HBN). In addition, we estimated brain age in PNC using a cross-validation framework. Next, we tested for associations between brain age gap and various aspects of psychopathology and cognitive performance. RESULTS: Our model was able to predict age in the independent test samples, with a model performance of r = 0.54 for the HBN test set, supporting consistency in functional connectivity patterns between samples and scanners. Linear models revealed a significant association between brain age gap and psychopathology in PNC, where individuals with a lower estimated brain age, had a higher overall symptom burden. These associations were not replicated in HBN. DISCUSSION: Our findings support the use of brain age prediction from fMRI-based connectivity. While requiring further extensions and validations, the approach may be instrumental for detecting brain phenotypes related to intrinsic connectivity and could assist in characterizing risk in non-typically developing populations.