Non-neural BOLD variability in block and event-related paradigms

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability.     

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Functional magnetic resonance imaging blood-oxygenation-level-dependent (fMRI-BOLD) signal representing neural activity may be optimized by discriminating MR signal components related to neural activity and those related to intrinsic properties of the cortical vasculature. The objective of this study was to reduce the hemodynamic change independent of neural activity to obtain a scaled fMRI-BOLD response using two factors, namely, low-frequency spectral amplitude (LFSA) and breath-hold amplitude (BHA). Ten subjects (age range, 22–38 years) were scanned during four task conditions: (a) rest while breathing room air, (b) bilateral finger tapping while breathing room air, (c) rest during a partial inspirational breath-hold, and (d) rest during moderate hypercapnia (breathing 5% CO₂, 20% O₂ and 75% N₂). In all subjects who breathed 5% CO₂, regions with significant BOLD response during breath-hold correlated significantly with the percent signal increase during 5% CO₂ inhalation. Finger-tapping-induced responses in the motor cortex were diminished to a similar extent after scaling using either LFSA or BHA. Inter- and intrasubject variation in the amplitude of the BOLD signal response reduced after hemodynamic scaling using LFSA or BHA. The results validated the hemodynamic amplitude scaling using LFSA with the earlier established BHA. LFSA free from motor-task contamination can be used to calibrate the fMRI-BOLD response in lieu of BHA or hypercapnia to minimize intra- and intersubject variation arising from vascular anatomy and vasodilative capacity.