Differential effects of iTBS over domain-general and language-specific brain regions on rule learning

Rule learning relies on both domain-general and language-specific neural systems, but how these systems interact during learning remains unclear. Guided by the variability-stability-flexibility (VSF) model, we combined intermittent theta-burst stimulation (iTBS) with fMRI to examine the effects of modulating the right dorsolateral prefrontal cortex (R DLPFC; a domain-general brain area) and left inferior frontal gyrus (L IFG; a language-specific brain area) during phase-structured word- and symbol-rule learning. Two groups of individuals received active iTBS, either over the R DLPFC or L IFG. A third group received sham iTBS over the vertex. Behaviorally, both active iTBS groups outperformed the sham group, with accuracy improving across phases. Full factorial and ROI analysis revealed phase-dependent activation shifts for both active iTBS groups, with performance improving across phases. Generalized Psychophysiological Interaction (gPPI) analyses showed that active iTBS applied over the R DLPFC enhanced large-scale network integration, while iTBS over the L IFG strengthened focal language-network specialization during word learning and promoted cross-system coordination during symbol learning. Dynamic Causal Modeling (DCM) demonstrated that active iTBS accelerated transitions from exploratory to flexible states, optimizing phase-dependent information flow. These findings suggest that successful rule learning arises from dynamic interactions between domain-general and language-specific neural mechanisms and that iTBS can selectively optimize these processes.