Desideri, D. | Search bioRxiv

bioRxiv2019

TMS-EEG signatures of glutamatergic neurotransmission in human cortex

Neuronal activity in the brain is regulated by an excitation-inhibition balance. Glutamate is the main excitatory neurotransmitter. Transcranial magnetic stimulation (TMS) evoked electroencephalographic (EEG) potentials (TEPs) represent a novel way to quantify pharmacological effects on neuronal activity in the human cortex. Here we tested TEPs under the influence of a single oral dose of two anti-glutamatergic drugs, perampanel, an AMPA-receptor antagonist, and dextromethorphan, an NMDA-receptor antagonist, and nimodipine, an L-type voltage-gated calcium channel blocker in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled, crossover design. Single-pulse TMS was delivered to the left motor cortex and TEPs were obtained pre-and post-drug intake. Dextromethorphan specifically increased the amplitude of the N45, a negative potential around 45 ms after the TMS pulse, while perampanel reduced the P70 amplitude in the non-stimulated hemisphere. Nimodipine and placebo had no effect on TEPs. These data 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 interhemispherically propagated activity reflected in the P70. These data are important to understand the physiology of TEPs as markers of excitability and propagated activity in the human cortex in health and disease.

neuroscience↗

bioRxiv2018

TMS-evoked EEG potentials from prefrontal and parietal cortex: reliability, site specificity, and effects of dextromethorphan

Measuring the brains response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers a unique insight into the local cortical circuits and networks activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP reliability, site-specificity, and sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (an NMDA receptor antagonist) or placebo across two sessions separated by at least a week in a double-blinded pseudo-randomised crossover design. At baseline, TEPs showed lower within-than between-subject variability for both stimulation sites across sessions, demonstrating the reliability of non-motor TEPs within individuals. There were differences in amplitude between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting that early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. TEPs were not altered following dextromethorphan compared to placebo, however low frequency resting oscillations were reduced in power. Our findings suggest that TEPs from PFC and PAR: 1) are reliable within and variable between individuals; 2) reflect stimulation site specific activity across early time periods (<80 ms); and 3) are not sensitive to changes in NMDA receptor-mediated neurotransmission.

neuroscience↗