4.6 Article

Metabolic underpinnings of activated and deactivated cortical areas in human brain

Journal

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 41, Issue 5, Pages 986-1000

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X21989186

Keywords

β -hydroxybutyrate (BHB); energy metabolism; γ -aminobutyrate (GABA); glutamate-glutamine cycle; lactate

Funding

  1. NCATS NIH HHS [UL1 TR001863] Funding Source: Medline
  2. NIMH NIH HHS [R01 MH067528, R01 MH109159] Funding Source: Medline
  3. NINDS NIH HHS [R01 NS100106] Funding Source: Medline

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Functional MRI can identify activated and deactivated brain regions in task paradigms, with changes in these patterns observed in diseases, leading to research into their biochemical and biophysical mechanisms. The study investigated metabolic differences in activated and deactivated brain regions, finding that BOLD responses are impacted oppositely by task-induced inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.
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 gamma-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.

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