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

Healthy aging is associated with mechanistic changes in gamma-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the human brain. While previous work mainly focused on magnetic resonance spectroscopy (MRS)-based GABA+ levels and transcranial magnetic stimulation (TMS)-based GABA(A) receptor (GABA(A)R) activity in the primary sensorimotor (SM1) cortex, the aim of the current study was to identify age-related differences in positron emission tomography (PET)-based GABA(A)R availability and its relationship with GABA+ levels (i.e. GABA with the contribution of macromolecules) and GABA(A)R activity. For this purpose, fifteen young (aged 20–28 years) and fifteen older (aged 65–80 years) participants were recruited. PET and MRS images were acquired using simultaneous time-of-flight PET/MR to evaluate age-related differences in GABA(A)R availability (distribution volume ratio with pons as reference region) and GABA+ levels. TMS was applied to identify age-related differences in GABA(A)R activity by measuring short-interval intracortical inhibition (SICI). Whereas GABA(A)R availability was significantly higher in the SM cortex of older as compared to young adults (18.5%), there were neither age-related differences in GABA+ levels nor SICI. A correlation analysis revealed no significant associations between GABA(A)R availability, GABA(A)R activity and GABA+ levels. Although the exact mechanisms need to be further elucidated, it is possible that a higher GABA(A)R availability in older adults is a compensatory mechanism to ensure optimal inhibitory functionality during the aging process.