Changes in working memory-related cortical responses following pediatric mild traumatic brain injury: A longitudinal fMRI study

Abstract

Persistent post-concussion symptoms (PPCS) lasting longer than 4 weeks affect 25% of children with mild traumatic brain injury (mTBI) or concussion. Working memory (WM) problems are a common complaint in children with PPCS. Despite normal function on traditional neuropsychological tests, these children exhibit aberrant cortical responses within the dorsolateral prefrontal cortex (dlPFC) and default mode network (DMN) regions – both of which are implicated in WM. Using a prospective, longitudinal cohort study design, we investigated changes in cortical fMRI responses within the dlPFC and DMN during an nback WM task at two timepoints: one and two months post-injury. Across these timepoints, the primary outcome was change in cortical activations (increase in BOLD) and deactivations (decrease in BOLD) of both dlPFC and DMN. Twenty-nine children (mean age 15.49 ± 2.15; 48.3% male) with fMRI scans at both timepoints were included, following data quality control. Student’s t-tests were used to examine cortical activations across time and task difficulty. ANCOVA F-tests examined cortical responses after removal of baseline across time, task difficulty and recovery. Volumes of interest (5 mm sphere) were placed in peak voxel regions of the DMN and dlPFC to compare cortical responses between recovered and unrecovered participants over time (one-way ANOVA). Between one and two months post-injury, we found significant increases in dlPFC activations and significant activations and deactivations in the DMN with increasing task difficulty, alongside improved task performance. Cortical responses of the DMN and bilateral dlPFC displayed increased intensity in recovered participants, together with improved attention and behavioural symptoms. Overall, our findings suggest evidence of neural compensation and ongoing cognitive recovery from pediatric TBI over time between one and two months post injury in children with PPCS. These results highlight the wider and persisting implications of mTBI in children, whose maturing brains are particularly vulnerable to TBI.