Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex

We investigated the relationship between neurochemical and hemodynamic responses as a function of image contrast in the human primary visual cortex (V1). Simultaneously acquired BOLD-fMRI and single voxel proton MR spectroscopy signals were measured in V1 of 24 healthy human participants of either sex at 7 tesla field strength, in response to presentations (64 s blocks) of different levels of image contrast (3%, 12.5%, 50%, 100%). Our results suggest that complementary measures of neurotransmission and energy metabolism are in partial agreement: BOLD and glutamate signals were linear with image contrast; however, a significant increase in glutamate concentration was evident only at the highest intensity level. In contrast, GABA signals were steady across all intensity levels. These results suggest that neurochemical concentrations are maintained at lower ranges of contrast levels, which match the statistics of natural vision, and that high stimulus intensity may be critical to increase sensitivity to visually modulated glutamate signals in the early visual cortex using MR spectroscopy.SIGNIFICANCE STATEMENT Glutamate and GABA are the major excitatory and inhibitory neurotransmitters of the brain. To better understand the relationship between MRS-visible neurochemicals, the BOLD signal change, and stimulus intensity, we measured combined neurochemical and BOLD signals (combined fMRI-MRS) to different image contrasts in human V1 at 7 tesla. While a linear change to contrast was present for both signals, the increase in glutamate was significant only at the highest stimulus intensity. These results suggest that hemodynamic and neurochemical signals reflect common metabolic markers of neural activity, whereas the mismatch at lower contrast levels may indicate a sensitivity threshold for detecting neurochemical changes during visual processing. Our results highlight the challenge and importance of reconciling cellular and metabolic measures of neural activity in the human brain.