Persistent Cognitive and Neuropsychiatric Sequelae of Mild Traumatic Brain Injury: Integrating Neuroinflammatory and Network Perspectives

Objectives: This paper aims to synthesize recent clinical and neurobiological findings on mild traumatic brain injury (mTBI), with a focus on the interrelationships among neuroinflammation, cognitive dysfunction, emotional regulation, and sleep disturbances. It seeks to challenge the assumption of mTBI as a transient event by highlighting persistent neuropsychological and affective consequences across civilian, military, and pediatric populations, and to advocate for integrated frameworks that address both biological and psychological dimensions of recovery. Methods: A literature-based integrative synthesis was conducted, drawing from peer-reviewed empirical studies (2015–2025) on mTBI, including longitudinal, cross-sectional, and experimental investigations. Articles were selected based on relevance to post-injury cognitive, affective, neurobiological, and sleep outcomes, with inclusion criteria requiring human participants with documented mTBI, quantitative or qualitative data on relevant domains, and publication in indexed journals (PubMed, PsycINFO, or ScienceDirect) between 2006 and 2025. Exclusion criteria eliminated studies on moderate/severe TBI without mild-specific analysis, animal-only studies without translational data, or those lacking validated neuropsychological methods. Convergent trends were qualitatively compared across studies using multivariate regression, network analysis, and effect magnitude. Results: mTBI was consistently linked to persistent cognitive inefficiencies in attention, working memory, and executive function; elevated affective symptoms including depression, anxiety, and PTSD (with comorbidity rates up to 39% in military samples); sleep disturbances in 40–65% of cases; and sustained neuroinflammatory activity with mitochondrial dysfunction. Network analyses revealed PTSD as a central hub interconnecting cognitive, somatic, and sleep domains, with attention deficits and fatigue acting as bridge symptoms that maintain chronic dysfunction. Conclusion: These findings reconceptualize mTBI as a multidimensional, chronic condition driven by dynamic biological-psychological interactions, underscoring the need for interdisciplinary interventions targeting neuroinflammation, cognitive rehabilitation, emotional regulation, and sleep to improve long-term outcomes.