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Differential Relationship of GABA and GLX in Dorsal vs. Ventral Prefrontal Cortex and Their Relationship To Age and Gender1Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States, 2Institute of Cognitive Science, Dept of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
Synopsis
MRS was employed in two regionally distinct prefrontal voxels (dorsal and ventral) in 62 adult females and 119 adolescents (60 males, 59 females) to determine the variations of GABA and GLX concentrations with regional specificity, participant gender, and age. The results indicate that levels of prefrontal neurotransmitter concentrations are influenced by age. Furthermore, the results suggest that the relationship between neurotransmitter levels can vary for adjacent portions of cortex, being more highly correlated for the dorsal than ventral voxel.
Introduction
Despite a growing emphasis on understanding how in vivo levels of neurotransmitter concentrations influence behavior, it still remains largely unknown the degree to which GABA (γ-aminobutyric acid) and GLX (glutamate + glutamine) levels 1) differ between subregions of the prefrontal cortex, 2) are modulated by gender, and 3) diverge in accordance with developmental status. In this current study, we employ MRS in two regionally distinct prefrontal voxels to the determine the degree to which relative levels of GABA and GLX differ in accordance with regional specificity, participant gender, and age.Methods
1H MRS sequences (PRESS (TR/TE 2000/35ms, 96 avgs) and MEGA-PRESS (TR/TE 2000/71ms, 384 (192 edit-on, 192 edit-off) averages), running on a Siemens Prisma 3T scanner (Siemens, Erlangen, Germany), were used to examine levels of GABA and GLX in a sample of 62 adult females (mean = 47.9 yrs, s.d.=6.62 yrs.) and 119 adolescents (60 males, mean age = 17.3 yrs, s.d=1.47; 59 females, mean age = 17.2 yrs, s.d.= 1.78) in two voxels in prefrontal cortex. The dorsal voxel was centered in superior frontal gyrus and dorsal portions of the middle frontal gyrus, while the ventral voxel was centered in the ventral portion of middle frontal gyrus and inferior frontal gyrus. The posterior edge of both voxels was positioned in front of the primary motor area and the anterior edge at the beginning of orbitofrontal cortex. Water reference spectra were also acquired. Spectra were processed using LCModel1 for PRESS spectra and Gannet2 for MEGA-PRESS spectra. Voxels were segmented using Gannet calls to SPM12 for grey matter, white matter, and CSF. The neurotransmitter levels in each voxel were adjusted for proportion of grey matter.Results
The raw data results are presented in Table 1.
In our adult (female) sample, increasing age was associated with decreased levels of neurotransmitter in the dorsal voxel. In contrast, for the ventral voxel, increasing age was associated with decreased levels of GABA and a trend toward increasing levels of GLX, as summarized in Table 2. For youth, no relationship with age was observed, and no gender differences were found.
The relationship between levels of each of the neurotransmitters (GABA, GLX) in each of the voxels was also examined. The levels of GABA and GLX within an individual were found to be more highly correlated for the dorsal voxel than the ventral voxel (adults: age-adjusted r=.72, Youth r=.70) as compared to the ventral voxel (adults: age adjusted .23/ youth .46). See Table 3.
While the trends are in similar directions for adults and youth, we then directly compared levels for the adults (all female) with our subsample of female youth for the relative ratio of GLX/GABA in each of the dorsal and ventral voxels. The GLX/GABA ratio for the dorsal voxel was significantly greater for female youth (Mean = 11.49, s.d. = 2.14) than our adults females (mean = 10.62, s.d. = 2.18) as determined by a Welch two-sample t-test t=2.1815, df = 113.7, p = .031). No effects were observed for the ventral voxel.
Discussion
These results indicate that levels of prefrontal neurotransmitter concentration are influenced by age, both as indicated by a correlation with age in our adult sample, and a difference in dorsal GLX/GABA ratio for adult vs. youth females. Furthermore, our results suggest that the relationship between neurotransmitter levels can vary for adjacent portions of cortex, being more highly correlated for the dorsal than ventral voxel.Acknowledgements
This work was supported by NIH grant MH100501.References
1. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993 Dec;30(6):672-9.
2. Edden RA, Puts NA, Harris AD, Barker PB, Evans CJ. Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid–edited MR spectroscopy spectra. J Magn Reson Imaging. 2014 Dec;40(6):1445-52.
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