Relationships between GABA+ and Glx concentrations with age and inhibition in healthy older adults
Poster No:
1961
Submission Type:
Late-Breaking Abstract Submission
Authors:
Ciara Treacy1
Institutions:
1University of the Sunshine Coast, Birtinya, Queensland
First Author:
Late Breaking Reviewer(s):
Introduction:
Successful inhibitory functioning relies upon the ability to voluntarily suppress impulses toward environmental interference and ignore competing distractions, thereby facilitating goal-oriented behaviour (Diamond, 2013). Cognitive changes observed during normal ageing can, in-part, be explained by neuroplasticity (Burke & Barnes, 2006), a process largely driven by the relative balance of predominant excitatory and inhibitory neurochemicals (Duncan et al., 2014). Within the cortex, glutamate and γ-aminobutyric acid (GABA), the major excitatory and inhibitory neurochemicals, respectively, are closely related to the excitation-inhibition (E/I) balance (Isaacson & Scanziani, 2011). While prior studies have linked sensorimotor (SM1) and prefrontal (PFC) GABA+ and Glx concentrations to various cognitive domains (for reviews see Li et al. (2022); Roalf et al. (2020)), neurochemical links to inhibitory sub-components have not been investigated in healthy older adults specifically (aged ≥ 50 years). Thus, in this study we investigated i) age relationships with neurochemical concentrations (GABA+ and Glx) and ii) the associations between these neurochemicals and inhibitory sub-components in the context of healthy ageing.
Methods:
This cross-sectional study was approved by the Human Research Ethics Committee of the University of the Sunshine Coast (S211620). All participants provided written, informed consent. Healthy older adults aged 50-85 years were recruited from the general community. Eligible participants were right hand dominant, English-speaking, cognitively/medically healthy, absent of any MRI contraindications and diagnoses pertaining to mild cognitive impairment, psychiatric disorders, or major neurological conditions. In total, 81 individuals satisfied eligibility screening. To measure inhibitory performance, three behavioural paradigms were administered via the PsyToolkit platform v3.4.2 (Stoet, 2010, 2017), specifically, the flanker task (i.e., inhibit distractors), Stroop task (i.e., inhibit interference), and go/no-go task (inhibit responding) were used, see Fig 1 for task diagrams. MRS data was acquired via a 3T Skyra (Siemens, Erlangen Germany) using a HERMES sequence, optimised for measuring GABA+ and GSH (Chan et al., 2016), and analysed using OSPREY's pipeline (see Fig 2). After data quality and accuracy verification, the final MRS sample was reduced to 71 participants for the SM1 dataset (mean age (SD) = 68.3 (±9.7) years;39 females) and 58 participants for the PFC dataset (mean age (SD) = 67.6 (±9.6) years;30 females). GABA+ and Glx concentrations are expressed as a ratio of creatine and phosphocreatine (tCr). i) Semi partial (age-neurochemical) and ii) partial (neurochemical-behaviour) corrections (rho) were performed using R Statistical Software v4.3.2 (R Core Team, 2023).
Results:
After correcting for gender and education, semi-partial correlations (rho) revealed no significant relationships between age and GABA+ or Glx concentrations in either the SM1 or PFC regions. Furthermore, through partial correlations (rho), after correcting for age, gender and education, we identified a significant negative relationship between SM1 Glx concentrations and go/no-go error rates (see Fig 2), such that greater concentrations of Glx in the SM1 region were associated with greater accuracy on the go/no-go task. No significant relationships were identified in the PFC region or with GABA+ concentrations.
Conclusions:
The null age-neurochemical results suggest that GABA+ and Glx may not uniformly decline during healthy ageing. This finding suggests that the relationship between older age and neurochemistry may be more nuanced than previously reported. In addition, our neurochemical-behavioural findings provide neurochemically-and-spatially specific evidence that SM1 Glx concentrations may be important for response inhibition. This result indicates a functional role for the glutamatergic system in supporting inhibition over the normal course of ageing.
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making 2
Lifespan Development:
Aging
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Neurophysiology of Imaging Signals
Novel Imaging Acquisition Methods:
MR Spectroscopy 1
Keywords:
Aging
Cognition
GABA
Glutamate
Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
Neurotransmitter
NORMAL HUMAN
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
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4. Duncan, N. W. (2014). Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—a review of multimodal imaging studies. Neurosci Biobehav Rev, 47, 36-52.
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6. Li, H. (2022). The role of MRS-assessed GABA in human behavioral performance. Progress in neurobiology, 212, 102247-102247.
7. R Core Team. (2023). R: A Language and Environment for Statistical Computing. In R Foundation for Statistical Computing.
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