The impact of GABAergic drugs on TMS-induced brain oscillations in human motor cortex

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2017-12, Vol.163, p.1-12
• Main Authors: Premoli, Isabella, Bergmann, Til O., Fecchio, Matteo, Rosanova, Mario, Biondi, Andrea, Belardinelli, Paolo, Ziemann, Ulf
• Format: Article
• Language: English
• Subjects: Alprazolam; Baclofen; Brain; Cortex (frontal); Cortex (motor); Cortex (somatosensory); Diazepam; Drug dosages; EEG; Electroencephalography; Excitability; Experiments; GABA; Human behavior; Inhibition; Magnetic fields; Medical research; Menstruation; Muscles; Neuromodulation; Neurosciences; Oscillations; Pharmaco-TMS-EEG; Pyramidal tracts; Synchronization; Transcranial magnetic stimulation; Zolpidem; γ-Aminobutyric acid A receptors; γ-Aminobutyric acid B receptors
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2017.09.023

Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30–200 ms after TMS) synchronization in the α- and β-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200–400 ms) α- and β-desynchronization over the stimulated and contralateral sensorimotor cortex. As GABAergic inhibition plays an important role in shaping oscillatory brain activity, we sought here to understand if GABAergic inhibition contributes to these TMS-induced oscillations. We tested single oral doses of alprazolam, diazepam, zolpidem (positive modulators of the GABAA receptor), and baclofen (specific GABAB receptor agonist). Diazepam and zolpidem enhanced, and alprazolam tended to enhance while baclofen decreased the early α-synchronization. Alprazolam and baclofen enhanced the early β-synchronization. Baclofen enhanced the late α-desynchronization, and alprazolam, diazepam and baclofen enhanced the late β-desynchronization. The observed GABAergic drug effects on TMS-induced α- and β-band oscillations were not explained by drug-induced changes on corticospinal excitability, muscle response size, or resting-state EEG power. Our results provide first insights into the pharmacological profile of TMS-induced oscillatory responses of motor cortex. •The response to TMS of M1 is composed of evoked and induced oscillatory activity.•TMS induced early α-/β-synchronization and late α-/β-desynchronization in M1.•GABAAergic vs. GABABergic drugs had opposite effects on early α-synchronization.•GABAAergic and GABABergic drugs enhanced the late β-desynchronization.