ArticleFrontiers in human neuroscience2026
State-dependent dual-site prefrontal TMS bidirectionally modulates working-memory accuracy.
Article in Frontiers in human neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Working memory (WM) is a core cognitive function that is both mechanistically tractable and clinically relevant, making it a prime target for noninvasive neuromodulation. However, transcranial magnetic stimulation (TMS) studies targeting the dorsolateral prefrontal cortex (DLPFC) have yielded variable WM outcomes, possibly because single-site protocols fail to engage the distributed network dynamics that support WM and because effects depend on momentary brain states. Here, we tested whether dual-site sequential TMS, excitatory intermittent theta-burst stimulation (iTBS) over left DLPFC combined with inhibitory continuous theta-burst stimulation (cTBS) over medial prefrontal cortex (mPFC), produces state-dependent modulation of WM performance compared with single-site DLPFC stimulation alone. Thirty-seven healthy adults completed a within-subjects protocol with intermixed 0-back and 2-back WM conditions. Self-reported fatigue before each task run served as a coarse indicator of the participant's cognitive state. Bayesian linear mixed models revealed a clear state-dependent pattern: in the high-load 2-back condition, dual-site stimulation improved accuracy when participants reported low fatigue but impaired accuracy when they reported high fatigue. No reliable effects were found for the 0-back condition or for reaction time. These findings demonstrate that dual-site prefrontal TMS can bidirectionally modulate WM accuracy relative to single-site stimulation depending on the participant's cognitive state, highlighting the importance of state-aware and network-sensitive stimulation approaches for cognitive enhancement.
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