Functional Connectivity Changes in Traumatic Brain Injury: A Systematic Review and Coordinate-Based Meta-Analysis of...

Traumatic brain injury (TBI) is associated with widespread disruptions in functional connectivity (FC), yet how these alterations vary by injury severity remains unclear. Traditional classification systems fail to capture network-level dysfunction, limiting prognostic accuracy and targeted rehabilitation strategies. The aim of this study was to systematically evaluate fMRI-detected FC alterations after mild, moderate-severe, and severe TBI using coordinate-based meta-analysis and network-level mapping.

A systematic search of MEDLINE/PubMed, Embase, and Web of Science was conducted to identify studies examining FC changes in TBI using fMRI. This review was not funded or prospectively registered. Studies were stratified by TBI severity and time since injury. Significant peak Montreal Neurological Institute coordinates were extracted, matched to the Yeo-17 brain network atlas, and analyzed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). Study quality and evidence level were assessed using an adapted NIH Quality Assessment Tool and the Oxford Centre for Evidence-Based Medicine criteria. Eligible studies included adult participants with TBI assessed using resting-state or task-based fMRI; studies lacking severity classification or involving pediatric populations were excluded.

Seventy-six studies were included, totaling 5,064 participants (2,993 patients with TBI, 1,914 controls; mean age 35.5 vs 35.0 years; 37.6% female overall). Mild TBI (mTBI) was the most common severity (n = 59 studies; 77.6%). Twenty-two studies contributed data for meta-analysis: 15 with resting-state fMRI and 7 with task-based fMRI. Aggregated peak coordinates most frequently mapped to subcomponents of the default mode (22.9%), ventral attention (18.8%), and somatomotor (10.1%) networks in mTBI and to the frontoparietal (36%), ventral attention (20%), and dorsal attention (14.7%) networks in moderate-severe/severe TBI. SDM-PSI identified uncorrected clusters in default mode and frontoparietal regions in mTBI and moderate-severe/severe TBI, respectively, but no clusters survived family-wise error rate correction (standardized mean difference Z score range -1.986 to 3.911, p < 0.05 uncorrected). Heterogeneity was low across analyses (I² < 21%).

FC changes after TBI potentially involve large-scale brain networks such as the default mode, attention, and executive control networks in a severity-dependent and phase-dependent manner. Although meta-analysis revealed consistent patterns, corrected statistical significance was not achieved, highlighting the need for larger, harmonized data sets and standardized analysis pipelines in future research.