Age-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS.

Healthy aging involves changes in gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. Previous research focused on magnetic resonance spectroscopy (MRS) measurements of GABA+ levels and transcranial magnetic stimulation (TMS) assessments of GABAA receptor (GABAAR) activity in the primary sensorimotor cortex (SM1). Our study aimed to explore age-related differences in GABAAR availability using positron emission tomography (PET) and its relationship with GABA+ levels and GABAAR activity.

We recruited fifteen young adults (20-28 years) and fifteen older adults (65-80 years). Simultaneous PET/MR scans were used to measure GABAAR availability (distribution volume ratio with the pons as a reference region) and GABA+ levels. TMS was employed to assess GABAAR activity by evaluating short-interval intracortical inhibition (SICI).

The results showed significantly higher GABAAR availability in the SM cortex of older adults compared to young adults, by 18.5%. However, there were no age-related differences in GABA+ levels or SICI. Correlation analysis revealed no significant connections between GABAAR availability, GABAAR activity, and GABA+ levels.

While the exact mechanisms remain unclear, it is plausible that the increased GABAAR availability in older adults serves as a compensatory mechanism to maintain optimal inhibitory function during the aging process. Further research is needed to fully understand these dynamics.

Neuroimage. 2021 Feb 1;226:117536. doi: 10.1016/j.neuroimage.2020.117536. Epub 2020 Nov 10.