Gamma-transcranial alternating current stimulation and theta-burst stimulation: inter-subject variability and the role of BDNF

Andrea Guerra, Francesco Asci, Alessandro Zampogna, Valentina D'Onofrio, Simona Petrucci, Monia Ginevrino, Alfredo Berardelli, Antonio Suppa

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OBJECTIVE: The main limitation of neuromodulation techniques is inter-subject variability. Combining theta-burst stimulation (TBS) with gamma-transcranial alternating current stimulation (γ-tACS) allows to shape cortical plasticity. However, it is unknown whether γ-tACS modifies TBS-induced response variability. In this study, we measured the inter-subject variability of TBS-γ tACS and controlled the effect of the Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism.

METHODS: Intermittent TBS (iTBS)-sham tACS, iTBS-γ tACS, continuous TBS (cTBS)-sham tACS, and cTBS-γ tACS were applied in randomised sessions. Inter-subject variability was measured using grand average and clustering methods. TBS-γ tACS effects on motor evoked potentials (MEP) were compared between Val/Val and Met carriers.

RESULTS: We found that γ-tACS boosted iTBS-induced MEP facilitation and cancelled cTBS-induced MEP depression. Grand average analysis showed that γ-tACS prominently increased the percentage of iTBS responders and cTBS non-responders. The clustering method demonstrated that TBS-γ tACS response varied between subjects, a phenomenon unrelated to the BDNF genotype.

CONCLUSIONS: Enhancing γ oscillations through tACS boosts iTBS-induced LTP-like plasticity and suppresses cTBS-induced LTD-like plasticity of the primary motor cortex in a reliable manner. The BDNF Val66Met polymorphism does not influence these effects.

SIGNIFICANCE: Since γ-tACS significantly increases the number of iTBS responders, it may be used in clinical settings.

Original languageEnglish
Pages (from-to)2691-2699
Number of pages9
JournalClin. Neurophysiol.
Issue number11
Publication statusPublished - Nov 2020


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