Title | Age-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Cuypers K, Hehl M, van Aalst J, Chalavi S, Mikkelsen M, Van Laere K, Dupont P, Mantini D, Swinnen SP |
Journal | Neuroimage |
Volume | 226 |
Pagination | 117536 |
Date Published | 2021 Feb 01 |
ISSN | 1095-9572 |
Keywords | Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Magnetic Resonance Spectroscopy, Male, Multimodal Imaging, Positron-Emission Tomography, Receptors, GABA-A, Sensorimotor Cortex, Transcranial Magnetic Stimulation, Young Adult |
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 GABAA receptor (GABAAR) 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 GABAAR availability and its relationship with GABA+ levels (i.e. GABA with the contribution of macromolecules) and GABAAR 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 GABAAR availability (distribution volume ratio with pons as reference region) and GABA+ levels. TMS was applied to identify age-related differences in GABAAR activity by measuring short-interval intracortical inhibition (SICI). Whereas GABAAR 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 GABAAR availability, GABAAR activity and GABA+ levels. Although the exact mechanisms need to be further elucidated, it is possible that a higher GABAAR availability in older adults is a compensatory mechanism to ensure optimal inhibitory functionality during the aging process. |
DOI | 10.1016/j.neuroimage.2020.117536 |
Alternate Journal | Neuroimage |
PubMed ID | 33186716 |
PubMed Central ID | PMC7894275 |
Grant List | P41 EB015909 / EB / NIBIB NIH HHS / United States R01 EB016089 / EB / NIBIB NIH HHS / United States R01 EB023963 / EB / NIBIB NIH HHS / United States |