Pharmaco-TMS-EEG: Establishing a novel tool for measuring excitability in human cerebral cortex
Final Report Abstract
The current project has substantially contributed to advancing our knowledge in characterizing the TMS-evoked EEG potentials by testing the effects of CNS active drugs with specific modes of action on TEP amplitudes. The most important novel findings can be summarized as follows: 1. The P25 is regulated by VGSCs. Blockers (carbamazepine) reduce the P25 amplitude at the site of stimulation. This is similar to the increase in motor threshold and reduction of MEP amplitude by VGSC blockers. In addition, P25 amplitude and MEP amplitude correlate. Therefore, the P25 likely reflects excitation of corticospinal neurons by TMS. 2. The N45 does not only reflect GABAAergic inhibitory postsynaptic potentials but a balance with glutamatergic excitatory postsynaptic potentials, as the NMDA-receptor antagonist dextromethorphan increased N45 amplitude, similar to positive allosteric modulators at the GABAA-receptor, such as diazepam and alprazolam. 3. The P70 was affected, out of all tested drugs so far, only by perampanel. This may indicate that the P70 reflects propagated glutamatergic excitation. Findings are consistent with exaggerated P70 potentials in particular types of epilepsy. 4. VGSC blockers also reduce the P180. But this finding may be qualified by possible contamination of late TEPs by non-specific peripherally evoked auditory and somatosensory evoked potentials and will require further experimental testing. In conclusion, the aims of this project were all achieved. The reported pharmaco- physiological characterization of TEPs will facilitate utilization of TMS-EEG in neuropsychiatric disorders with altered excitability and/or network connectivity.
Publications
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(2019) Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS- EEG study. Hum Brain Mapp 40:1276-1289
Darmani G, Bergmann TO, Zipser C, Baur D, Müller-Dahlhaus F, Ziemann U
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(2019) Pharmacophysiology of TMS-evoked EEG potentials: A mini-review. Brain Stimul 12:829-831
Darmani G, Ziemann U
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(2019) TMS-EEG signatures of glutamatergic neurotransmission in human cortex
König F, Belardinelli P, Liang C, Desideri D, Müller-Dahlhaus F, Gordon PC, Zipser C, Zrenner C, Ziemann U
