title: Characterization of the influence of age on GABAAand glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.
abstract: Gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmissions in the prefrontal cortex decreases with age. Further, cognitive function mediated through the dorsolateral prefrontal cortex (DLPFC) also declines with age. Although neuroimaging studies have demonstrated decreased levels of these substances, direct neurophysiological data investigating the effect of aging in the DLPFC in human subjects is lacking. The advent of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) has allowed for the assessment of functional neurotransmission in vivo. In the present study, we examined short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in a group of older adults (> 60 yrs) to evaluate the strength of GABAAand glutamate-mediated neurotransmission in the DLPFC, compared to younger adults (18-59 yrs). Older adults showed an increase of amplitude of N100 by the SICI paradigm, while N45 amplitude was increased and N100 amplitude was decreased by ICF. Moreover, these modulations significantly correlated with age. Our findings provide evidence for age-related alterations of excitatory and inhibitory functions in the prefrontal cortex in healthy adults. Future studies may aim to explore these neurophysiological relationships in the DLPFC in pathological forms of aging that affect cortical functioning such as mild cognitive impairment and Alzheimer's disease.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noda
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Zomorrodi
authors.affiliation: Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and the Alfred, Melbourne 3004, Australia.
authors.forename: Robin F H
authors.initials: RF
authors.lastname: Cash
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Mera S
authors.initials: MS
authors.lastname: Barr
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Faranak
authors.initials: F
authors.lastname: Farzan
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, Toronto, M5T 2S8, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: TMS–EEG; aging effect; dorsolateral prefrontal cortex (DLPFC); intracortical facilitation (ICF); short interval intracortical inhibition (SICI)