ABSTRACT Background Emerging evidence suggests that low‐frequency neural oscillations are dynamically regulated by consciousness levels, with the recovery of low cortical activity potentially serving as a neurophysiological substrate for conscious emergence. Targeted enhancement of these low‐frequency rhythms in patients with disorders of consciousness (DoC) may constitute a promising neuromodulation strategy to facilitate consciousness recovery in severe brain injury. Objective This study systematically examined the neurophysiological effects of intermittent theta‐burst stimulation (iTBS), specifically its potential to enhance low‐frequency cortical activity and promote consciousness recovery in patients with DoC. Through multimodal neural assessments, we aimed to elucidate the mechanistic relationship between iTBS‐induced neural oscillation modulation and behavioral manifestations of consciousness improvement. Results This prospective cohort study enrolled 30 patients with DoC, of whom 18 completed the full intervention protocol. Two‐way repeated‐measures analysis of variance revealed significant group × time interaction effects on the Coma Recovery Scale‐Revised (CRS‐R) scores, F (1, 16) = 6.543, p = 0.021. Post hoc simple effects analysis demonstrated significant temporal improvement in the active transcranial magnetic stimulation (TMS) group, F (1, 16) = 36.463, p < 0.001, with mean CRS‐R scores increased from 9.300 ± 1.320 at baseline to 11.700 ± 1.409 post‐intervention ( p < 0.001). Conversely, sham stimulation revealed statistically nonsignificant changes (9.845 ± 1.476 versus 10.750 ± 1.575, p = 0.067). Neurophysiological assessments revealed emerging neurophysiological changes in the iTBS group, including enhanced resting‐state low‐frequency oscillations (delta: 21.642% increase, p = 0.449; theta: 6.800% increase, p = 0.789) and augmented auditory‐evoked responses (phrase‐level 22.917% increase, p = 0.280; syllable‐level: 22.963% increase, p = 0.504), suggesting potential neural plasticity mechanisms that require further validation. Conclusion Collectively, this study established iTBS targeting the left dorsolateral prefrontal cortex as a clinically effective and well‐tolerated neuromodulation approach for consciousness rehabilitation in patients with DoC, with therapeutic effects mediated by iTBS‐induced enhancement of thalamocortical low‐frequency oscillations. Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03385278. Registered on October 24, 2017
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