No 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.

Using a cross-sectional design, we aimed to identify the effect of aging on sensorimotor function and cortical motor representations of two intrinsic hand muscles, as well as the course and timing of those changes. Furthermore, the link between cortical motor representations, sensorimotor function, and intracortical inhibition and facilitation was investigated. Seventy-seven participants over the full adult lifespan were enrolled. For the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscle, cortical motor representations, GABAA-mediated short-interval intracortical inhibition (SICI), and glutamate-mediated intracortical facilitation (ICF) were assessed using transcranial magnetic stimulation over the dominant primary motor cortex. Additionally, participants' dexterity and force were measured. Linear, polynomial, and piecewise linear regression analyses were conducted to identify the course and timing of age-related differences. Our results demonstrated variation in sensorimotor function over the lifespan, with a marked decline starting around the mid-thirties. Furthermore, an age-related reduction in cortical motor representation volume and maximal MEP of the FDI, but not for ADM, was observed, occurring mainly until the mid-forties. Area of the cortical motor representation did not change with advancing age. Furthermore, cortical motor representations, sensorimotor function, and measures of intracortical inhibition and facilitation were not interrelated.

Dual-site transcranial magnetic stimulation (ds-TMS) is well suited to investigate the causal effect of distant brain regions on the primary motor cortex, both at rest and during motor performance and learning. However, given the broad set of stimulation parameters, clarity about which parameters are most effective for identifying particular interactions is lacking. Here, evidence describing inter- and intra-hemispheric interactions during rest and in the context of motor tasks is reviewed. Our aims are threefold: (1) provide a detailed overview of ds-TMS literature regarding inter- and intra-hemispheric connectivity; (2) describe the applicability and contributions of these interactions to motor control, and; (3) discuss the practical implications and future directions. Of the 3659 studies screened, 109 were included and discussed. Overall, there is remarkable variability in the experimental context for assessing ds-TMS interactions, as well as in the use and reporting of stimulation parameters, hindering a quantitative comparison of results across studies. Further studies examining ds-TMS interactions in a systematic manner, and in which all critical parameters are carefully reported, are needed.