fMRI BOLD turnover (TBOLD) as a proxy for neuroinflammation

Inflammation is associated with detrimental health outcomes, including deleterious effects on the brain. We have recently introduced a new measure of brain function reflecting the moment-to-moment change, or turnover, in the resting-state blood oxygen level-dependent (BOLD) signal, or TBOLD. In previous studies, an increase of TBOLD with age was found to be associated with a concomitant decrease in brain volume, whereas both changes were absent in individuals carrying the neuroprotective human leukocyte antigen (HLA) allele DRB1*13:02. Given that TBOLD reflects neurovascular coupling and that neuroinflammation is involved in brain aging, we hypothesized that TBOLD could reflect neuroinflammation. Here, we tested this hypothesis by assessing the association of TBOLD with known inflammatory markers in a large sample of 1,390 healthy participants from the Human Connectome Project on Aging/Aging Adult Brain Connectome (AABC). We found a highly significant, positive association between TBOLD and the inflammatory marker C-reactive protein (CRP). Furthermore, we found a highly significant association between TBOLD and interleukin-6 (IL-6) in a smaller group of 97 participants for whom IL-6 measurements were available. These findings document significant positive associations of TBOLD to systemic inflammatory markers, lending support to the hypothesis that TBOLD may serve as a proxy for neuroinflammation. NEW & NOTEWORTHY Here we provide evidence for the hypothesis that resting-state fMRI BOLD turnover (TBOLD) could serve as a proxy for neuroinflammation by documenting its positive association with two major inflammatory markers, namely C-reac-tive protein in a large sample of healthy participants (n = 1,390, 36-90 þ yr old) and interleukin-6 in a smaller subsample (n = 97). The measuring of TBOLD (a simple process) would assist in determining the neuroinflammatory brain status in health and disease.