Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Modulates Electroencephalographic Functional Connectivity in Alzheimer’s Disease

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear. Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment. Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared. Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group. Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.