Brain Age Revisited: Investigating the State vs. Trait Hypotheses of EEG-derived Brain-Age Dynamics with Deep Learning

The brain's biological age has been considered as a promising candidate for a neurologically significant biomarker. However, recent results based on longitudinal magnetic resonance imaging data have raised questions on its interpretation. A central question is whether an increased biological age of the brain is indicative of brain pathology and if changes in brain age correlate with diagnosed pathology (state hypothesis). Alternatively, could the discrepancy in brain age be a stable characteristic unique to each individual (trait hypothesis)? To address this question, we present a comprehensive study on brain aging based on clinical EEG, which is complementary to previous MRI-based investigations. We apply a state-of-the-art Temporal Convolutional Network (TCN) to the task of age regression. We train on recordings of the Temple University Hospital EEG Corpus (TUEG) explicitly labeled as non-pathological and evaluate on recordings of subjects with non-pathological as well as pathological recordings, both with examinations at a single point in time and repeated examinations over time. Therefore, we created four novel subsets of TUEG that include subjects with multiple recordings: I) all labeled non-pathological; II) all labeled pathological; III) at least one recording labeled non-pathological followed by at least one recording labeled pathological; IV) similar to III) but with opposing transition (first pathological then non-pathological). The results show that our TCN reaches state-of-the-art performance in age decoding with a mean absolute error of 6.6 years. Our extensive analyses demonstrate that the model significantly underestimates the age of non-pathological and pathological subjects (-1 and -5 years, paired t-test, p <= 0.18 and p <= 0.0066). Furthermore, the brain age gap biomarker is not indicative of pathological EEG.