The contribution of the vascular architecture and cerebrovascular reactivity to the BOLD signal formation across cortical depth.

Assessment of neuronal activity using blood oxygenation level-dependent (BOLD) is confounded by how the cerebrovascular architecture modulates hemodynamic responses. To understand brain function at the laminar level, it is crucial to distinguish neuronal signal contributions from those determined by the cortical vascular organization. Therefore, our aim was to investigate the purely vascular contribution in the BOLD signal by using vasoactive stimuli and compare that with neuronal-induced BOLD responses from a visual task. To do so, we estimated the hemodynamic response function (HRF) across cortical depth following brief visual stimulations under different conditions using ultrahigh-field (7 Tesla) functional (f)MRI. We acquired gradient-echo (GE)-echo-planar-imaging (EPI) BOLD, containing contributions from all vessel sizes, and spin-echo (SE)-EPI BOLD for which signal changes predominately originate from microvessels, to distinguish signal weighting from different vascular compartments. Non-neuronal hemodynamic changes were induced by hypercapnia and hyperoxia to estimate cerebrovascular reactivity and venous cerebral blood volume ( $CBV{v}_{O_2}$ ). Results show that increases in GE HRF amplitude from deeper to superficial layers coincided with increased macrovascular $CBV{v}_{O_2}$ . $CBV{v}_{O_2}$ -normalized GE-HRF amplitudes yielded similar cortical depth profiles as SE, thereby possibly improving specificity to neuronal activation. For GE BOLD, faster onset time and shorter time-to-peak were observed toward the deeper layers. Hypercapnia reduced the amplitude of visual stimulus-induced signal responses as denoted by lower GE-HRF amplitudes and longer time-to-peak. In contrast, the SE-HRF amplitude was unaffected by hypercapnia, suggesting that these responses reflect predominantly neurovascular processes that are less contaminated by macrovascular signal contributions.