Multi-modal normalization of resting-state using local physiology reduces changes in functional connectivity patterns observed in mTBI patients

Abstract Blood oxygenation level dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) may serve as a sensitive marker to identify possible changes in the architecture of large-scale networks following mild traumatic brain injury (mTBI). Differences in functional connectivity (FC) measurements derived from BOLD rs-fMRI may however be confounded by changes in local cerebrovascular physiology and neurovascular coupling mechanisms, without changes in the underlying neuronally driven connectivity of networks. In this study, multi-modal neuroimaging data including BOLD rs-fMRI, baseline cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR; acquired using a hypercapnic gas breathing challenge) were collected in 23 subjects with reported mTBI (14.6 ± 14.9 months post-injury) and 27 age-matched healthy controls. Despite no group differences in CVR within the networks of interest (P > 0.05, corrected), significantly higher CBF0 was documented in the mTBI subjects (P