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.

Important for the interpretation of BOLD fMRI data is a linear relationship between the BOLD response and the underlying neural activity: increased BOLD responses should reflect proportionate increases in the underlying neural activity. While previous studies have demonstrated a linear relationship between the peak amplitude of the BOLD response and neural activity in primary visual cortex (V1), these studies have used stimuli that excite large areas of cortex, and the linearity of the BOLD response has not been demonstrated when only a small patch of cortex is stimulated. The BOLD response to isolated Gabor patches of increasing contrast was measured with gradient echo (GE) BOLD and spin echo (SE) BOLD at 7 T. Our primary finding is notable spatial heterogeneity of the BOLD contrast response, particularly for the GE BOLD data, resulting in a more reliably linear relationship between BOLD data and estimated neural responses in the center of the cortical representations of the individual Gabor patches than near the edges. A control experiment with larger sinusoidal grating patches confirms that the observed sensitivity to voxel selection in the regions of interest-based analysis is unique to the small stimuli.

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Theoretical studies suggest that the visual system uses prior knowledge of visual objects to recognize them in visual clutter, and posit that the strategies for recognizing objects in clutter may differ depending on whether or not the object was learned in clutter to begin with. We tested this hypothesis using functional magnetic resonance imaging (fMRI) of human subjects. We trained subjects to recognize naturalistic, yet novel objects in strong or weak clutter. We then tested subjects' recognition performance for both sets of objects in strong clutter. We found many brain regions that were differentially responsive to objects during object recognition depending on whether they were learned in strong or weak clutter. In particular, the responses of the left fusiform gyrus (FG) reliably reflected, on a trial-to-trial basis, subjects' object recognition performance for objects learned in the presence of strong clutter. These results indicate that the visual system does not use a single, general-purpose mechanism to cope with clutter. Instead, there are two distinct spatial patterns of activation whose responses are attributable not to the visual context in which the objects were seen, but to the context in which the objects were learned.

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