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

• Published in: Clinical neurophysiology Vol. 131; no. 11; pp. 2691 - 2699
• Main Authors: Guerra, Andrea, Asci, Francesco, Zampogna, Alessandro, D'Onofrio, Valentina, Petrucci, Simona, Ginevrino, Monia, Berardelli, Alfredo, Suppa, Antonio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2020
• Subjects: BDNF; Gamma; Inter-subject variability; Neurology; Plasticity; tACS; Theta-burst stimulation; tACS; Gamma; Theta-burst stimulation; BDNF; Inter-subject variability; Plasticity
• ISSN: 1388-2457; 1872-8952; 1872-8952
• DOI: 10.1016/j.clinph.2020.08.017

•γ-tACS increases the percentage of responders to intermittent TBS from 50% to 89.3%.•γ-tACS decreases the percentage of responders to continuous TBS from 46.2% to 0%.•The Val66Met polymorphism in the BDNF gene does not influence the effects of γ-tACS. 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. 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. 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. 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. Since γ-tACS significantly increases the number of iTBS responders, it may be used in clinical settings.