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

Abstract

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.