Phase‐dependent local brain states determine the impact of image‐guided transcranial magnetic stimulation on motor network electroencephalographic synchronization

• Published in: The Journal of physiology Vol. 600; no. 6; pp. 1455 - 1471
• Main Authors: Momi, Davide, Ozdemir, Recep A., Tadayon, Ehsan, Boucher, Pierre, Di Domenico, Alberto, Fasolo, Mirco, Shafi, Mouhsin M., Pascual‐Leone, Alvaro, Santarnecchi, Emiliano
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2022
• Subjects: Brain; brain‐state dependent effect; Cortex (motor); cortico‐cortical connectivity; EEG; Electroencephalography - methods; Evoked Potentials, Motor - physiology; Humans; Magnetic fields; Motor Cortex - physiology; Neural networks; Neuroimaging; Oscillations; Reproducibility of Results; Sensorimotor system; structural connectivity; Substantia alba; Synchronization; TMS‐EEG; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - methods; μ‐rhythm; structural connectivity; μ-rhythm; TMS-EEG; brain-state dependent effect; cortico-cortical connectivity
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/JP282393

Recent studies have synchronized transcranial magnetic stimulation (TMS) application with pre‐defined brain oscillatory phases showing how brain response to perturbation depends on the brain state. However, none have investigated whether phase‐dependent TMS can possibly modulate connectivity with homologous distant brain regions belonging to the same network. In the framework of network‐targeted TMS, we investigated whether stimulation delivered at a specific phase of ongoing brain oscillations might favour stronger cortico‐cortical (c‐c) synchronization of distant network nodes connected to the stimulation target. Neuronavigated TMS pulses were delivered over the primary motor cortex (M1) during ongoing electroencephalography recording in 24 healthy individuals over two repeated sessions 1 month apart. Stimulation effects were analysed considering whether the TMS pulse was delivered at the time of a positive (peak) or negative (trough) phase of μ‐frequency oscillation, which determines c‐c synchrony within homologous areas of the sensorimotor network. Diffusion weighted imaging was used to study c‐c connectivity within the sensorimotor network and identify contralateral regions connected with the stimulation spot. Depending on when during the μ‐activity the TMS‐pulse was applied (peak or trough), its impact on inter‐hemispheric network synchrony varied significantly. Higher M1–M1 phase‐lock synchronization after the TMS‐pulse (0–200 ms) in the μ‐frequency band was found for trough compared to peak stimulation trials in both study visits. Phase‐dependent TMS delivery might be crucial not only to amplify local effects but also to increase the magnitude and reliability of the response to the external perturbation, with implications for interventions aimed at engaging more distributed functional brain networks. Key points Synchronized transcranial magnetic stimulation (TMS) pulses with pre‐defined brain oscillatory phases allow evaluation of the impact of brain states on TMS effects. TMS pulses over M1 at the negative peak of the μ‐frequency band induce higher phase‐lock synchronization with interconnected contralateral homologous regions. Cortico‐cortical synchronization changes are linearly predicted by the fibre density and cross‐section of the white matter tract that connects the two brain regions. Phase‐dependent TMS delivery might be crucial not only to amplify local effects but also to increase the magnitude and reliability of within‐network synchronization. figure legend TMS pulses delivered over M1 at the negative peak of μ‐frequency band induces higher phase‐lock synchronization with interconnected contralateral homologous regions. The the fiber density and cross‐section of the white matter tract that connect the two motor cortices predicts such cortico‐cortical synchronization changes. Phase‐dependent TMS delivery might be crucial to increase magnitude and reliability of within‐network synchronization.