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Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation
Authors:Andrea Guerra,Antonio Suppa,Matteo Bologna,Valentina D&#x  Onofrio,Edoardo Bianchini,Peter Brown,Vincenzo Di Lazzaro,Alfredo Berardelli
Affiliation:1. Department of Human Neuroscience, Sapienza University of Rome, Viale dell''Università 30, 00185, Rome, Italy;2. IRCCS Neuromed Institute, Via Atinense 18, 86077, Pozzilli, IS, Italy;3. Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom;4. Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico, via Álvaro del Portillo 21, 00128, Rome, Italy
Abstract:

Background

Transcranial Alternating Current Stimulation (tACS) consists in delivering electric current to the brain using an oscillatory pattern that may entrain the rhythmic activity of cortical neurons. When delivered at gamma frequency, tACS modulates motor performance and GABA-A-ergic interneuron activity.

Objective

Since interneuronal discharges play a crucial role in brain plasticity phenomena, here we co-stimulated the primary motor cortex (M1) in healthy subjects by means of tACS during intermittent theta-burst stimulation (iTBS), a transcranial magnetic stimulation paradigm known to induce long-term potentiation (LTP)-like plasticity.

Methods

We measured and compared motor evoked potentials before and after gamma, beta and sham tACS-iTBS. While we delivered gamma-tACS, we also measured short-interval intracortical inhibition (SICI) to detect any changes in GABA-A-ergic neurotransmission.

Results

Gamma, but not beta and sham tACS, significantly boosted and prolonged the iTBS-induced after-effects. Interestingly, the extent of the gamma tACS-iTBS after-effects correlated directly with SICI changes.

Conclusions

Overall, our findings point to a link between gamma oscillations, interneuronal GABA-A-ergic activity and LTP-like plasticity in the human M1. Gamma tACS-iTBS co-stimulation might represent a new strategy to enhance and prolong responses to plasticity-inducing protocols, thereby lending itself to future applications in the neurorehabilitation setting.
Keywords:tACS  Gamma  TMS  Plasticity  Interneurons  GABA-A  M1  primary motor cortex  RMT  resting motor threshold  tACST  ranscranial Alternating Current Stimulation  TMST  ranscranial Magnetic Stimulation  SICI  Short-interval intracortical inhibition  iTBS  intermittent theta-burst stimulation  γ  gamma  β  beta
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