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

TitleAge-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS
Publication TypeJournal Article
Year of Publication2021
AuthorsCuypers K, Hehl M, van Aalst J, Chalavi S, Mikkelsen M, Van Laere K, Dupont P, Mantini D, Swinnen SP
JournalNeuroimage
Volume226
Pagination117536
Date Published2021 Feb 01
ISSN1095-9572
KeywordsAdult, 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.

DOI10.1016/j.neuroimage.2020.117536
Alternate JournalNeuroimage
PubMed ID33186716
PubMed Central IDPMC7894275
Grant ListP41 EB015909 / EB / NIBIB NIH HHS / United States
R01 EB016089 / EB / NIBIB NIH HHS / United States
R01 EB023963 / EB / NIBIB NIH HHS / United States