Trajectories of intrinsic connectivity one year post pediatric mild traumatic brain injury: Neural injury superimposed on neurodevelopment

Abstract

The developing brain undergoes rapid changes throughout middle childhood and adolescence. The disambiguation of long-term changes in intrinsic activity following pediatric mild traumatic brain injury (pmTBI) from typical development can therefore only be ascertained in longitudinal studies with large sample size and at least three serial assessments. A comprehensive clinical battery and resting-state fMRI data were collected approximately 1-week (N = 263; 8-18 years old), 4-months (N = 192) and 1-year (N = 153) post-injury, with identical visits in a large cohort (N = 228) of age- and sex-matched healthy controls (HC). Results indicated persistent frontocerebellar and thalamic connectivity changes up to 1-year post-injury in pmTBI relative to controls (P's < .001), with similar longitudinal connectivity trajectories (i.e., typical neurodevelopment). Alterations in precuneal midline connectivity (p's < .05) and occupancy of a default mode/limbic dynamic brain state were present only up to 4-months (p's < .001) rather than 1-year (p's > .44) post-injury. However, absent group differences at 1-year post-injury may be explained as pseudo-normalization due to altered longitudinal connectivity trajectories in pmTBI associated with neurodevelopment. Persistent alterations of precuneal connectivity were also associated with lower executive function and long-term memory scores. In conclusion, pmTBI may result in chronic changes to both static and dynamic intrinsic connectivity which further interact with typical neurodevelopment. Longer follow-up studies may be needed to unravel this interaction.