title: Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG.
abstract: Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAAreceptor-mediated inhibition and glutamatergic excitatory transmission, respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from the dorsolateral prefrontal cortex (DLPFC) using combined TMS and electroencephalography (TMS-EEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS-evoked potentials (TEPs) and spectral power modulation. Subsequently, these paradigms were applied in the DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation, respectively) of P30 and P60 TEP amplitude, which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, whereas P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long-interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall, the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing noninvasive measures of glutamatergic and GABAAreceptor-mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Division of Neurology, Department of Medicine, University of Toronto, Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.|Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and The Alfred, Melbourne, VIC, 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, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, 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, ON, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Zomorrodi
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Division of Neurology, Department of Medicine, University of Toronto, Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Radhu
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, 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, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and The Alfred, Melbourne, VIC, Australia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, ON, 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, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, 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, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
mesh_terms: D000328:Adult; D000071080:Cortical Excitability; D004569:Electroencephalography; D005071:Evoked Potentials; D019054:Evoked Potentials, Motor; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition; D017397:Prefrontal Cortex / Q000502:physiology*; D009435:Synaptic Transmission; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid