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

Abstract

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.

Cross-Frequency Coupling and Intelligent Neuromodulation

“…This could be relevant in terms of identifying at-risk populations and trialing both pharmacological and non-pharmacological neuroprotective therapies [ 77 , 78 ]. Interestingly, θ – γ coupling has been reported to be enhanced by the use of CBS [ 79 , 80 ]. For example, Etter et al.…”

High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats

“…HF-rTMS over the DLPFC can improve cognitive function in patients with MCI and AD (Chou et al, 2020). Previous studies have shown that rTMS over the DLPFC modified cognitive performances via modulating brain functional connectivity of DLPFC and other brain regions in MCI or AD patients (Guo et al, 2021;Esposito et al, 2022). Thus, rTMS-induced activity and neural plasticity underlie cognitive improvement.…”

Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer’s Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study

“…Another application of MRI in rTMS clinical trials, including in [ 13 ], is for the neuronavigation of the magnetic coil during treatment, in which MRI scans of AD participants are utilized to localize a target area of the brain, in the case of our study, to target stimulation to the dorsolateral prefrontal cortex (DLPFC) bilaterally. The DLPFC is the most common brain region for the treatment of AD using rTMS [ 14 ] due to its broad and complex connections with cortical and deeper subcortical brain structures [ 15 ] and its executive role in planning and decision -making, most notably in working memory [ 16 , 17 ]. However, to date, no study has investigated the potential of baseline MRI analysis to predict rTMS treatment efficacy in the AD population.…”