Objective <p>This double-blinded randomized trial investigated the effects of accelerated intermittent theta-burst stimulation (iTBS) and adaptive cognitive training on brain function in 24 patients with amnestic mild cognitive impairment (aMCI).</p> Methods <p>Participants received real (n=12) or sham (n=12) iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) thrice daily alongside cognitive training for 14 days. The Montreal Cognitive Assessment (MoCA), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and functional near-infrared spectroscopy (fNIRS) during rest and N-back tasks, which measure cognitive function and brain activity respectively, were administered pre-and post-intervention.</p> Results <p>The active group demonstrated significant cognitive improvement. Compared to sham controls, postintervention fNIRS results revealed reduced global brain activation during the 1-back task in the active group, particularly in the left prefrontal cortex, and the brain activation correlated with reaction time. In the 2-back task after treatment, the active group exhibited decreased activation in the right motor cortex, while the sham group showed increased activation in the left motor cortex. The overall brain connectivity in the sham group enhanced following the intervention, with significant differences in the correlations between the left prefrontal cortex and left motor cortex between groups.</p> Conclusion <p>These findings suggest that the combined intervention can effectively promote cognitive performance and brain function in aMCI patients. iTBS causes enhanced functional engagement of the left DLPFC, which further facilitates neural efficiency and restores the capacity to modulate the allocation of neural resources rather than relying on global compensatory hyperactivation. These may be the underlying neural mechanisms for memory improvement in aMCI patients (Chinese Clinical Trial Registry: ChiCTR2400087943).</p>