Single-trial variability in event-related BOLD signals

Most current analysis methods for fMRI data assume a priori knowledge of the time course of the hemodynamic response (HR) to experimental stimuli or events in brain areas of interest. In addition, they typically assume homogeneity of both the HR and the non-HR "noise" signals, both across brain regions and across similar experimental events. When HRs vary unpredictably, from area to area or from trial to trial, an alternative approach is needed. Here, we use Infomax independent component analysis (ICA) to detect and visualize variations in single-trial HRs in event-related fMRI data. Six subjects participated in four fMRI sessions each in which ten bursts of 8-Hz flickering-checkerboard stimulation were presented for 0.5-s (short) or 3-s (long) durations at 30-s intervals. Five axial slices were acquired by a Bruker 3-T magnetic resonance imager at interscan intervals of 500 ms (TR). ICA decomposition of the resulting blood oxygenation level-dependent (BOLD) data from each session produced an independent component active in primary visual cortex (V1) and, in several sessions, another active in medial temporal cortex (MT/V5). Visualizing sets of BOLD response epochs with novel BOLD-image plots demonstrated that component HRs varied substantially and often systematically across trials as well as across sessions, subjects, and brain areas. Contrary to expectation, in four of the six subjects the V1 component HR contained two positive peaks in response to short-stimulus bursts, while components with nearly identical regions of activity in long-stimulus sessions from the same subjects were associated with single-peaked HRs. Thus, ICA combined with BOLD-image visualization can reveal dramatic and unforeseen HR variations not apparent to researchers analyzing their data with event-related response averaging and fixed HR templates.