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Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG.
Neuropsychopharmacology 2017; 42(2):502-511N

Abstract

Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAA receptor-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 GABAA receptor-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+Show Affiliations

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.Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada. Department of Psychiatry, University of Toronto, Toronto, ON, Canada.Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada.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.Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada.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.Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and The Alfred, Melbourne, VIC, Australia.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.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27461082

Citation

Cash, Robin F H., et al. "Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 42, no. 2, 2017, pp. 502-511.
Cash RF, Noda Y, Zomorrodi R, et al. Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG. Neuropsychopharmacology. 2017;42(2):502-511.
Cash, R. F., Noda, Y., Zomorrodi, R., Radhu, N., Farzan, F., Rajji, T. K., ... Blumberger, D. M. (2017). Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 42(2), pp. 502-511. doi:10.1038/npp.2016.133.
Cash RF, et al. Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG. Neuropsychopharmacology. 2017;42(2):502-511. PubMed PMID: 27461082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG. AU - Cash,Robin F H, AU - Noda,Yoshihiro, AU - Zomorrodi,Reza, AU - Radhu,Natasha, AU - Farzan,Faranak, AU - Rajji,Tarek K, AU - Fitzgerald,Paul B, AU - Chen,Robert, AU - Daskalakis,Zafiris J, AU - Blumberger,Daniel M, Y1 - 2016/07/27/ PY - 2016/04/20/received PY - 2016/06/22/revised PY - 2016/07/10/accepted PY - 2016/7/28/pubmed PY - 2018/1/6/medline PY - 2016/7/28/entrez SP - 502 EP - 511 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 42 IS - 2 N2 - Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAA receptor-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 GABAA receptor-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. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/27461082/Characterization_of_Glutamatergic_and_GABAA_Mediated_Neurotransmission_in_Motor_and_Dorsolateral_Prefrontal_Cortex_Using_Paired_Pulse_TMS_EEG_ L2 - http://dx.doi.org/10.1038/npp.2016.133 DB - PRIME DP - Unbound Medicine ER -