Drivers of resting-state fMRI heterogeneity in traumatic brain injury across injury characteristics and imaging methods: a systematic review and semiquantitative analysis.

Traumatic brain injury (TBI) is common and costly. Although neuroimaging modalities such as resting-state functional MRI (rsfMRI) promise to differentiate injured from healthy brains and prognosticate long-term outcomes, the field suffers from heterogeneous findings. To assess whether this heterogeneity stems from variability in the TBI populations studied or the imaging methods used, and to determine whether a consensus exists in this literature, we performed the first systematic review of studies comparing rsfMRI functional connectivity (FC) in patients with TBI to matched controls for seven canonical brain networks across injury severity, age, chronicity, population type, and various imaging methods. Searching PubMed, Web of Science, Google Scholar, and ScienceDirect, 1,105 manuscripts were identified, 50 fulfilling our criteria. Across these manuscripts, 179 comparisons were reported between a total of 1,397 patients with TBI and 1,179 matched controls. Collapsing across injury characteristics, imaging methods, and networks, there were roughly equal significant to null findings and increased to decreased connectivity differences reported. Whereas most factors did not explain these mixed findings, stratifying across severity and chronicity, separately, showed a trend of increased connectivity at higher severities and greater chronicities of TBI. Among methodological factors, studies were more likely to find connectivity differences when scans were longer than 360 s, custom image processing pipelines were used, and when patients kept their eyes open versus closed during scans. We offer guidelines to address this variability, focusing on aspects of study design and rsfMRI acquisition to move the field toward reproducible results with greater potential for clinical translation.