Metabolite activity in the anterior cingulate cortex during a painful stimulus using functional MRS

Sci Rep. 2020 Nov 5;10(1):19218. doi: 10.1038/s41598-020-76263-3.


To understand neurochemical brain responses to pain, proton magnetic resonance spectroscopy (1H-MRS) is used in humans in vivo to examine various metabolites. Recent MRS investigations have adopted a functional approach, where acquisitions of MRS are performed over time to track task-related changes. Previous studies suggest glutamate is of primary interest, as it may play a role during cortical processing of noxious stimuli. The objective of this study was to examine the metabolic effect (i.e., glutamate) in the anterior cingulate cortex during noxious stimulation using fMRS. The analysis addressed changes in glutamate and glutamate + glutamine (Glx) associated with the onset of pain, and the degree by which fluctuations in metabolites corresponded with continuous pain outcomes. Results suggest healthy participants undergoing tonic noxious stimulation demonstrated increased concentrations of glutamate and Glx at the onset of pain. Subsequent reports of pain were not accompanied by corresponding changes in glutamate of Glx concentrations. An exploratory analysis on sex revealed large effect size changes in glutamate at pain onset in female participants, compared with medium-sized effects in male participants. We propose a role for glutamate in the ACC related to the detection of a noxious stimulus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Functional Neuroimaging
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism*
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Pain / diagnostic imaging
  • Pain / metabolism*
  • Young Adult


  • Glutamine
  • Glutamic Acid