Neurochemical and BOLD Responses during Neuronal Activation Measured in the Human Visual Cortex at 7 Tesla

TLDR

Previous studies have reported small changes in lactate, glutamate, aspartate, and glucose during prolonged cortical stimulation, but their relationship to BOLD‑fMRI signals remains unclear. This study aimed to characterize how these metabolite concentration changes relate to BOLD‑fMRI signals during a visual stimulation block paradigm. Using 7‑Tesla fMRS with a short‑echo semi‑LASER sequence and concurrent fMRI, data were collected from 12 volunteers. Group analysis showed lactate and glutamate rose by ~30% and ~3% while aspartate and glucose fell by ~5% and ~16%; BOLD signals correlated positively with glutamate and lactate, were inversely related to baseline GABA, and overall demonstrated a linear relationship between metabolic and BOLD responses under strong sensory input.

Abstract

Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level—dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26±0.06 μmol/g (∼30%) and 0.28±0.03 μmol/g (∼3%), respectively, while aspartate and glucose decreased by 0.20±0.04 μmol/g (∼5%) and 0.19±0.03 μmol/g (∼16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms.