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Mild traumatic brain injuries (mTBIs) commonly occur in children and adolescents and can result in persistent cognitive symptoms. The neurophysiological changes that underlie persistent post-concussive symptoms (PPCS) have not been characterized. Our objective was to compare working-memory related functional magnetic resonance imaging (fMRI) response in children with persistent symptoms after mTBI at one month post-injury to children with typical recovery and healthy controls. This was a prospective, controlled cohort study of children with mTBI at one month post-injury. PPCS was defined as children with a 10-point increase in their post-concussion symptom inventory score (compared with pre-injury score) at one month post-injury and a two-point increase in at least two symptom categories compared with pre-injury. One hundred and seven participants (60 PPCS, 30 recovered mTBI, and 17 controls) with a mean age of 14.2 years (standard deviation [SD] 2.5) (44% male) were assessed 38 (SD 5.9) days after mTBI. The primary outcome measures were visuospatial n-back working memory task performance and fMRI blood oxygen level dependent (BOLD) signal change. Children with PPCS had decreased activation relative to children with typical recovery in the posterior cingulate and precuneus during the one-back working memory condition, despite similar task performance. Differences in cortical activation in children with PPCS at one month highlight the persistent neurobiological consequences of pediatric mTBI on working memory cortical activation. These findings encourage recommendations to avoid contact sports and provide continued care at school for children with persistent symptoms at one month post-injury. [ABSTRACT FROM AUTHOR]