TMS-EEG signatures of glutamatergic neurotransmission in human cortex
Abstract Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (de...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-87533-z |
| _version_ | 1818424821711634432 |
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| author | Paolo Belardinelli Franca König Chen Liang Isabella Premoli Debora Desideri Florian Müller-Dahlhaus Pedro Caldana Gordon Carl Zipser Christoph Zrenner Ulf Ziemann |
| author_facet | Paolo Belardinelli Franca König Chen Liang Isabella Premoli Debora Desideri Florian Müller-Dahlhaus Pedro Caldana Gordon Carl Zipser Christoph Zrenner Ulf Ziemann |
| author_sort | Paolo Belardinelli |
| collection | DOAJ |
| description | Abstract Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance. |
| first_indexed | 2024-12-14T14:04:08Z |
| format | Article |
| id | doaj.art-7ef4d5033f584e31b11159a369683d7b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:04:08Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7ef4d5033f584e31b11159a369683d7b2022-12-21T22:58:37ZengNature PortfolioScientific Reports2045-23222021-04-0111111410.1038/s41598-021-87533-zTMS-EEG signatures of glutamatergic neurotransmission in human cortexPaolo Belardinelli0Franca König1Chen Liang2Isabella Premoli3Debora Desideri4Florian Müller-Dahlhaus5Pedro Caldana Gordon6Carl Zipser7Christoph Zrenner8Ulf Ziemann9Department of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenDepartment of Neurology and Stroke, University of TübingenAbstract Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance.https://doi.org/10.1038/s41598-021-87533-z |
| spellingShingle | Paolo Belardinelli Franca König Chen Liang Isabella Premoli Debora Desideri Florian Müller-Dahlhaus Pedro Caldana Gordon Carl Zipser Christoph Zrenner Ulf Ziemann TMS-EEG signatures of glutamatergic neurotransmission in human cortex Scientific Reports |
| title | TMS-EEG signatures of glutamatergic neurotransmission in human cortex |
| title_full | TMS-EEG signatures of glutamatergic neurotransmission in human cortex |
| title_fullStr | TMS-EEG signatures of glutamatergic neurotransmission in human cortex |
| title_full_unstemmed | TMS-EEG signatures of glutamatergic neurotransmission in human cortex |
| title_short | TMS-EEG signatures of glutamatergic neurotransmission in human cortex |
| title_sort | tms eeg signatures of glutamatergic neurotransmission in human cortex |
| url | https://doi.org/10.1038/s41598-021-87533-z |
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