GABA and glutamate in the preterm neonatal brain: In-vivo measurement by magnetic resonance spectroscopy

Neuroimage. 2021 Sep;238:118215. doi: 10.1016/j.neuroimage.2021.118215. Epub 2021 May 28.


Cognitive and behavioral disabilities in preterm infants, even without obvious brain injury on conventional neuroimaging, underscores a critical need to identify the subtle underlying microstructural and biochemical derangements. The gamma-aminobutyric acid (GABA) and glutamatergic neurotransmitter systems undergo rapid maturation during the crucial late gestation and early postnatal life, and are at-risk of disruption after preterm birth. Animal and human autopsy studies provide the bulk of current understanding since non-invasive specialized proton magnetic resonance spectroscopy (1H-MRS) to measure GABA and glutamate are not routinely available for this vulnerable population due to logistical and technical challenges. We review the specialized 1H-MRS techniques including MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS), special challenges and considerations needed for interpretation of acquired data from the developing brain of preterm infants. We summarize the limited in-vivo preterm data, highlight the gaps in knowledge, and discuss future directions for optimal integration of available in-vivo approaches to understand the influence of GABA and glutamate on neurodevelopmental outcomes after preterm birth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Magnetic Resonance Spectroscopy
  • Neuroimaging
  • gamma-Aminobutyric Acid / metabolism*


  • Glutamic Acid
  • gamma-Aminobutyric Acid