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Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study.
Hum Brain Mapp 2019; 40(4):1276-1289HB

Abstract

Brain responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) are emergent noninvasive markers of neuronal excitability and effective connectivity in humans. However, the underlying physiology of these TMS-evoked EEG potentials (TEPs) is still heavily underexplored, impeding a broad application of TEPs to study pathology in neuropsychiatric disorders. Here we tested the effects of a single oral dose of three antiepileptic drugs with specific modes of action (carbamazepine, a voltage-gated sodium channel (VGSC) blocker; brivaracetam, a ligand to the presynaptic vesicle protein VSA2; tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor) on TEP amplitudes in 15 healthy adults in a double-blinded randomized placebo-controlled crossover design. We found that carbamazepine decreased the P25 and P180 TEP components, and brivaracetam the N100 amplitude in the nonstimulated hemisphere, while tiagabine had no effect. Findings corroborate the view that the P25 represents axonal excitability of the corticospinal system, the N100 in the nonstimulated hemisphere propagated activity suppressed by inhibition of presynaptic neurotransmitter release, and the P180 late activity particularly sensitive to VGSC blockade. Pharmaco-physiological characterization of TEPs will facilitate utilization of TMS-EEG in neuropsychiatric disorders with altered excitability and/or network connectivity.

Authors+Show Affiliations

Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany.Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30549127

Citation

Darmani, Ghazaleh, et al. "Effects of Antiepileptic Drugs On Cortical Excitability in Humans: a TMS-EMG and TMS-EEG Study." Human Brain Mapping, vol. 40, no. 4, 2019, pp. 1276-1289.
Darmani G, Bergmann TO, Zipser C, et al. Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study. Hum Brain Mapp. 2019;40(4):1276-1289.
Darmani, G., Bergmann, T. O., Zipser, C., Baur, D., Müller-Dahlhaus, F., & Ziemann, U. (2019). Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study. Human Brain Mapping, 40(4), pp. 1276-1289. doi:10.1002/hbm.24448.
Darmani G, et al. Effects of Antiepileptic Drugs On Cortical Excitability in Humans: a TMS-EMG and TMS-EEG Study. Hum Brain Mapp. 2019;40(4):1276-1289. PubMed PMID: 30549127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study. AU - Darmani,Ghazaleh, AU - Bergmann,Til O, AU - Zipser,Carl, AU - Baur,David, AU - Müller-Dahlhaus,Florian, AU - Ziemann,Ulf, Y1 - 2018/12/13/ PY - 2018/07/28/received PY - 2018/09/21/revised PY - 2018/10/17/accepted PY - 2018/12/15/pubmed PY - 2018/12/15/medline PY - 2018/12/15/entrez KW - TMS-evoked EEG response KW - brivaracetam KW - carbamazepine KW - electroencephalography KW - excitability KW - human cortex KW - tiagabine KW - transcranial magnetic stimulation SP - 1276 EP - 1289 JF - Human brain mapping JO - Hum Brain Mapp VL - 40 IS - 4 N2 - Brain responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) are emergent noninvasive markers of neuronal excitability and effective connectivity in humans. However, the underlying physiology of these TMS-evoked EEG potentials (TEPs) is still heavily underexplored, impeding a broad application of TEPs to study pathology in neuropsychiatric disorders. Here we tested the effects of a single oral dose of three antiepileptic drugs with specific modes of action (carbamazepine, a voltage-gated sodium channel (VGSC) blocker; brivaracetam, a ligand to the presynaptic vesicle protein VSA2; tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor) on TEP amplitudes in 15 healthy adults in a double-blinded randomized placebo-controlled crossover design. We found that carbamazepine decreased the P25 and P180 TEP components, and brivaracetam the N100 amplitude in the nonstimulated hemisphere, while tiagabine had no effect. Findings corroborate the view that the P25 represents axonal excitability of the corticospinal system, the N100 in the nonstimulated hemisphere propagated activity suppressed by inhibition of presynaptic neurotransmitter release, and the P180 late activity particularly sensitive to VGSC blockade. Pharmaco-physiological characterization of TEPs will facilitate utilization of TMS-EEG in neuropsychiatric disorders with altered excitability and/or network connectivity. SN - 1097-0193 UR - https://www.unboundmedicine.com/medline/citation/30549127/Effects_of_antiepileptic_drugs_on_cortical_excitability_in_humans:_A_TMS-EMG_and_TMS-EEG_study L2 - https://doi.org/10.1002/hbm.24448 DB - PRIME DP - Unbound Medicine ER -