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TMS-EEG Signatures of GABAergic Neurotransmission in the Human Cortex
Open accessAbstract
Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.
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Cited by
Rossini, P. M., Burke, D., Chen, R., Cohen, L. G., Daskalakis, Z., Di Iorio, R., Di Lazzaro, V., Ferreri, F., Fitzgerald, P. B., George, M. S., et al. (2015) · Clinical Neurophysiology · doi:10.1016/j.clinph.2015.02.001 · Cited by 2,753
Self-citationSiebner, H. R., Funke, K., Aberra, A. S., Antal, A., Bestmann, S., Chen, R., Classen, J., Davare, M., Di Lazzaro, V., Fox, P. T., et al. (2022) · Clinical Neurophysiology · doi:10.1016/j.clinph.2022.04.022 · Cited by 566
Self-citationClinical utility and prospective of TMS–EEG
Tremblay, S., Rogasch, N. C., Premoli, I., Blumberger, D. M., Casarotto, S., Chen, R., Di Lazzaro, V., Farzan, F., Ferrarelli, F., Fitzgerald, P. B., et al. (2019) · Clinical Neurophysiology · doi:10.1016/j.clinph.2019.01.001 · Cited by 472
Self-citationPlasticity induced by non-invasive transcranial brain stimulation: a position paper
Huang, Y.-Z., Lu, M.-K., Antal, A., Classen, J., Nitsche, M., Ziemann, U., Ridding, M., Hamada, M., Ugawa, Y., Jaberzadeh, S., et al. (2017) · Clinical Neurophysiology · doi:10.1016/j.clinph.2017.09.007 · Cited by 401
Self-citationThe non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies
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Metadata
- Authors
- Premoli, I., Castellanos, N., Rivolta, D., Belardinelli, P., Bajo, R., Zipser, C., Espenhahn, S., Heidegger, T., Müller-Dahlhaus, F., & Ziemann, U.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-04-16
- Volume
- 34
- Issue
- 16
- Pages
- 5603-5612
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1992885267
- Cited by
- 393
- References
- 57
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Premoli, I., Castellanos, N., Rivolta, D., Belardinelli, P., Bajo, R., Zipser, C., Espenhahn, S., Heidegger, T., Müller-Dahlhaus, F., & Ziemann, U. (2014). TMS-EEG Signatures of GABAergic Neurotransmission in the Human Cortex. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.5089-13.2014
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