Resting-State Brain Entropy Reveals Altered Neural Dynamics and Cognitive Associations in Mild Traumatic Brain Injury: A Longitudinal Study.

Mild traumatic brain injury (mTBI) is associated with persistent physical, cognitive, and emotional symptoms, yet the functional brain changes that accompany recovery remain incompletely understood. This longitudinal study investigated brain entropy (BEN), a resting-state measure of irregularity or complexity of spontaneous BOLD activity derived from resting-state functional magnetic resonance imaging (rs-fMRI), during the first year following mTBI. Data of rs-fMRI were acquired from 48 patients with mTBI at the acute (< 14 days), 6-month, and 12-month post-injury visits, and 34 healthy controls (HCs). BEN was quantified using sample entropy. Patients with mTBI also underwent behavioral assessments evaluating quality of life and cognitive function. Behavioral assessments demonstrated progressive improvements in patient-reported quality of life and objective cognitive performance. Cross-sectional analyses revealed dynamic, time-dependent alterations in BEN. Compared with HCs, patients with mTBI exhibited higher BEN in precuneus, temporal, occipital, and sensorimotor regions during the acute and 6-month stages, whereas lower BEN was observed in sensorimotor, occipital, and frontoparietal regions at the 12-month follow-up. Longitudinal analyses demonstrated progressive regional reductions in BEN over time. Several associations between longitudinal changes in regional BEN and cognitive performance were nominally significant, particularly in the precuneus, but none survived multiple comparison corrections. These findings indicate that mTBI recovery is accompanied by dynamic, regionally specific changes in resting state BOLD irregularity. BEN may therefore provide a promising imaging biomarker for tracking the evolving neural dynamics underlying recovery following mTBI.