Metabolic underpinnings of activated and deactivated cortical areas in human brain

Abstract

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.

Simultaneous detection of metabolite concentration changes, water BOLD signal and pH changes during visual stimulation in the human brain at 9.4T

“…12 Only one recently published study demonstrates the power of concurrent fMRI-fMRS measurements interleaving unsuppressed water acqusitions with water-suppressed J-difference editing acqusitions. 6 In this study, we demonstrated the BOLD induced line narrowing behavior due to brain activation in the MC water signal acquired simultaneously with the metabolite signals from the same voxel. The BOLD effect on water is easier to compute than on metabolites since metabolite peaks are overlapped by macromolecules and other metabolite resonances, which makes linewidths and peak heights determination challenging.…”

“…water-unsuppressed measurements in the same TR provide the closest link between hemodynamics and neurochemistry. 6,13,19,66 Since a 3D EPI sequence is used in the BOLD fMRI-MRS combining studies, activation maps with a high spatial resolution could be obtained.…”

“…So far, measurements combining fMRI-MRS or water-suppressed and water-unsuppressed measurements in the same TR provide the closest link between hemodynamics and neurochemistry. 6,13,19,66 Since a 3D EPI sequence is used in the BOLD fMRI-MRS combining studies, activation maps with a high spatial resolution could be obtained. Interleaving EPI and MRS may affect the M 0 relaxation process, may increase the temporal resolution of the MRS measurement due to SAR limitations, and potential eddy current effects from the EPI readout may influence MRS data quality.…”

“…4,5 Also, more recent studies use J-edited and long TE methods to look specifically at lactate, c-aminobutyric acid (GABA), and glutamate and glutamine (Glx) alterations under visual stimulation. [6][7][8] While editing and long TE sequences intrinsically remove overlapping signals, therefore enabling precise assessment of changes in Lac, GABA, and Glx, short TE non-edited measurements are advantageous because of high SNR and the simultaneous detection of a wide range of brain metabolites. Several short TE non-edited 1 H fMRS studies have previously been performed in the human brain under visual stimulation at an ultra-high field (UHF) strength of 7 T. [8][9][10][11][12][13][14][15][16][17] They consistently report increases of lactate (Lac) and glutamate (Glu) during stimulation.…”

Where functional MRI stops, metabolism starts

“…This can be measured using functional magnetic resonance spectroscopy (fMRS), a technique which quantifies chemical compounds within a three-dimensional volume. As recent studies show, combining BOLD-fMRI with fMRS that records glutamate and lactate concentrations can help to dissect the neural processes at play in active brain areas ( Mangia et al, 2007 ; Schaller et al, 2014 ; Ip et al, 2017 ; Boillat et al, 2020 ; Koush et al, 2021 ).…”