Optimizing Theta Burst Stimulation Protocols: A Computational Exploration of Novel Alpha-Beta and Alpha-Gamma...

This computational study aimed to optimize the theta burst stimulation (TBS) protocols by systematically exploring the effects of novel frequency couplings combining alpha-band bursts (10 Hz) with pulses in beta (21-29 Hz) and gamma (30-100 Hz) ranges on cortical excitability. Utilizing a revised calcium-dependent plasticity model, we simulated intermittent (iTBS) and continuous (cTBS) TBS after-effects under conventional (5 Hz burst, 50 Hz pulse), Nyffeler's modified (6 Hz burst, 30 Hz pulse), and proposed alpha-beta/gamma frequency couplings. Model robustness was assessed via sensitivity analyses. Novel alpha-beta/gamma couplings consistently induced more pronounced Motor-Evoked Potential (MEP) after-effects. For iTBS/cTBS, alpha-beta coupling (10 Hz burst, 21 Hz pulse) yielded the highest facilitatory/inhibitory effect (14.25/-93.17), markedly surpassing Nyffeler's (7.71/-8.81) and conventional (5.48/-5.35). Alpha-gamma coupling (10 Hz burst, 30 Hz pulse) also showed superior effects. Sensitivity and uncertainty analyses confirmed higher responsiveness. Coupling alpha-band bursts with targeted beta/gamma pulse frequencies markedly enhances the efficacy of TBS-induced cortical plasticity. These findings provide a strong computational rationale for empirical validation and potential clinical translation to improve neuromodulation precision in neuropsychiatric disorders. This work introduces promising optimized TBS protocols that may elevate therapeutic outcomes and reduce treatment variability, advancing non-invasive brain stimulation interventions.