Metabolite concentration changes associated with positive and negative BOLD responses in the human visual cortex: A functional MRS study at 7 Tesla

Abstract

Negative blood oxygenation-level dependent (BOLD) signal observed during task execution in functional magnetic resonance imaging (fMRI) can be caused by different mechanisms, such as a blood-stealing effect or neuronal deactivation. Electrophysiological recordings showed that neuronal deactivation underlies the negative BOLD observed in the occipital lobe during visual stimulation. In this study, the metabolic demand of such a response was studied by measuring local metabolite concentration changes during a visual checkerboard stimulation using functional magnetic resonance spectroscopy (fMRS) at 7 Tesla. The results showed increases of glutamate and lactate concentrations during the positive BOLD response, consistent with previous fMRS studies. In contrast, during the negative BOLD response, decreasing concentrations of glutamate, lactate and gamma-aminobutyric acid (GABA) were found, suggesting a reduction of glycolytic and oxidative metabolic demand below the baseline. Additionally, the respective changes of the BOLD signal, glutamate and lactate concentrations of both groups suggest that a local increase of inhibitory activity might occur during the negative BOLD response.

Keywords: Functional magnetic resonance imaging; brain metabolism; functional magnetic resonance spectroscopy; inhibition; negative blood oxygenation–level dependent; neurovascular coupling; positive blood oxygenation–level dependent; visual stimulation.

Figure 1.

fMRI results (p < .001 uncorrected) of representative participants in (a) the posBOLD group and (b) the negBOLD group. The inset images represent the checkerboards used to trigger the PBR and NBR. The red scale represents the PBR and the blue scale represents the NBR. The H¹-MRS VOIs are showed in green. An example of the fMRI acquisition slab is delineated in yellow. (c) Percentage change of BOLD signal inside the VOI used for fMRS for both the posBOLD and negBOLD groups. Each dot is a subject. The bar indicates the standard deviation (d) Linewidth change of the NAA peak measured as the FWHM of STIM-REST. (e) Percentage of voxels showing a positive (red) or negative (blue) signal in both posBOLD and negBOLD groups. The error bars represent the standard deviation. (f) Pooled averaged spectra of the last three minutes both STIM and REST periods for the posBOLD group in order to illustrate the BOLD effect on the NAA peak height and FWHM.

Figure 2.

Pooled averaged spectra of the last three minutes both STIM and REST periods for the (a) posBOLD and (b) negBOLD groups. STIM* is the linewidth corrected spectra. Only the posBOLD group was corrected for the BOLD effect as the effect was too small in the case of the negBOLD group. The bottom spectra represent the difference of individual spectra corresponding to the statistically significant metabolites.

Figure 3.

Time courses of the metabolites: (a and b) Glu, (c and d) Lac, and (e) GABA for the posBOLD (left graphs) and the negBOLD (right graphs) groups. The color-shaded areas are the periods of checkerboard stimulation. A moving average window of four-time points was applied to all the time courses. The error bars represent the standard error of the mean across participants.

Figure 4.

(a) Hypothetic scenario for the energetic costs measured via the BOLD amplitude for the baseline (gray screen), posBOLD, and negBOLD conditions. NegBOLD (I) represents the case when remote excitatory input is reduced triggering an overall decrease in both glutamatergic and GABAergic neuronal activity. NegBOLD (II) represents the case when local inhibition from GABAergic neurons increases resulting in an overall decrease of neuronal activity. (b) Scheme representing the proposed metabolic fluxes and steady-state concentrations between glutamatergic and GABAergic neurons and astrocytes. The red arrows represent the changes during the posBOLD condition and the blue arrows represent the changes in the negBOLD group. The arrows in dark colors correspond to the significant changes measured in the current study and in light colors are other assumed changes.