Effects of Intermittent Theta-Burst Stimulation over the Left Dorsolateral Prefrontal Cortex on Executive Function During Sustained Simulated Flight Operations: A Randomized Crossover Study Using a Flight–Cognitive Dual-Task Paradigm

Sustained flight operation load may compromise executive control in complex human–machine interaction environments. Intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) holds potential for modulating executive function, yet its effects on different executive components under sustained operational load remain unclear. This study employed a randomized, balanced, within-subject crossover design, enrolling 25 healthy male participants. Each participant completed three intervention conditions: Active iTBS, Sham iTBS, and No-stimulation. Each experimental session consisted of stimulation delivery, a 60-min cruising simulated flight, and a 30-min flight–cognitive dual-task phase. Primary outcomes were behavioral performance on the Go/No-Go, 3-back, and number-rule switching tasks; EEG microstates and prefrontal relative oxygenated hemoglobin (HbO) changes during the dual-task phase served as exploratory neurophysiological indices. Results showed that condition differences were concentrated in working memory updating and rule switching: compared with No-stimulation, Active iTBS shortened 3-back reaction time and reduced switch cost; compared with both No-stimulation and Sham iTBS, Active iTBS improved 3-back accuracy and number-rule switching accuracy; the switch-cost difference between Active and Sham iTBS did not reach significance (pBonferroni = 0.055). No significant condition effect was observed for the Go/No-Go task. EEG microstate analysis revealed task-specific changes: under the Active iTBS condition, the occurrence rate and temporal coverage of microstate D increased during the 3-back task; temporal coverage of microstate D increased during the number-rule switching task; no significant microstate changes were observed during the Go/No-Go task. Exploratory fNIRS analysis indicated that left-hemisphere and all-channel prefrontal HbO under Active iTBS was higher than under Sham iTBS in planned pairwise comparisons (pBonferroni < 0.03), but the corresponding condition main effects (p ≥ 0.065) and condition × hemisphere interaction (p = 0.919) were non-significant, and channel-level effects did not survive multiple-comparison correction. These findings suggest that, within the flight–cognitive dual-task paradigm, Active iTBS over the left DLPFC is associated with improvements in working memory and rule switching performance, accompanied by changes in microstate temporal organization during certain tasks. The microstate and fNIRS results provide exploratory neurophysiological observations and cannot establish causal relationships with the behavioral improvements.