Relationships between GABA + and Glx concentrations with age and inhibition in healthy older adults

Abstract

Inhibition represents a core executive function which underlies the ability to suppress interfering or distracting stimuli, thereby building resistance against task-irrelevant information. However, the impact of ageing on inhibitory functioning and the role of neuroplasticity - largely driven by predominant excitatory (glutamatergic) and inhibitory (GABAergic) neurochemicals – remains poorly understood. This study investigated age relationships with neurochemical concentrations (GABA + and Glx) and their associations with inhibitory sub-components in healthy ageing. Participants completed three inhibition tasks (flanker, Stroop, go/no-go), each measuring a different sub-component process, via the PsyToolkit platform. MRS data were acquired in the sensorimotor (SM1; n = 71, mean age (SD) = 68.3 (± 9.7) years, 39 females) and prefrontal (PFC; n = 58, mean age (SD) = 67.6 (± 9.6) years, 30 females) regions using a HERMES sequence and analysed using OSPREY’s pipeline. After correcting for gender and education, semi-partial correlations revealed no significant relationships between age and GABA + or Glx concentrations in either the SM1 or PFC. Furthermore, after correcting for age, gender and education, partial correlations identified a significant negative relationship between SM1 Glx concentrations and go/no-go error rates, such that greater concentrations of SM1 Glx were associated with greater go/no-go accuracy. The null age-neurochemical results suggest that GABA + and Glx may not uniformly decline during healthy ageing, indicating a more nuanced relationship 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 role for the glutamatergic system in supporting inhibition, independent of age.