Abstract
Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs) are independent of the amplitude of the neural signals that give rise to them. The validity of this assumption is particularly important for techniques that use fMRI to resolve sub-second timing distinctions between responses, in order to make inferences about the ordering of neural processes. Whether or not the detailed shape of the HRF is independent of neural response amplitude remains an open question, however. We performed experiments in which we measured responses in primary visual cortex (V1) to large, contrast-reversing checkerboards at a range of contrast levels, which should produce varying amounts of neural activity. Ten subjects (ages 22–52) were studied in each of two experiments using 3 Tesla scanners. We used rapid, 250 ms, temporal sampling (repetition time, or TR) and both short and long inter-stimulus interval (ISI) stimulus presentations. We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time (long- and medium-ISI experiments, but not the short-ISI experiment). Thus, stimuli that produce larger neural responses, as indexed by HRF amplitude, also produced HRFs with shorter onsets. The relationship between amplitude and latency was strongest in voxels with lowest mean-normalized variance (i.e., parenchymal voxels). The onset differences observed in the longer-ISI experiments are likely attributable to mechanisms of neurovascular coupling, since they are substantially larger than reported differences in the onset of action potentials in V1 as a function of response amplitude.
Highlights
Most analyses of neuroimaging data assume a fixed shape for the measured response
Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs) are independent of the amplitude of the neural signals that give rise to them
We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time
Summary
In BOLD fMRI, for example, standard analyses measure neural activity by regressing data onto a cannonical hemodynamic response function (HRF); larger responses are assumed to be scaled copies of smaller ones. While scaling holds at least roughly (e.g., Boynton et al, 1996; Janz et al, 2001; Olman et al, 2004; Heckman et al, 2007; Li et al, 2008) it remains to be investigated in fine detail. It is unknown whether the timing of fMRI responses changes as neural activity increases.
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