Cortical laminar resting-state signal fluctuations scale with the hypercapnic blood oxygenation level-dependent response

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level‐dependent (BOLD) response. This is achieved by scaling, using information from a perfusion‐sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath‐hold task. In this work, we seek for a validation of the use of the resting‐state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth‐dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia‐induced signal changes (tSDhc) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc ( R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M ( R2 = 0.62 ± 0.19). Laminar profiles of RSFA‐normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.