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Alzheimer Disease / Disease Models, Animal / Alzheimer's Disease · Journal article
Experimental Neurology · July 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical mechanistic study in transgenic Alzheimer's disease mice demonstrating that 40 Hz repetitive transcranial magnetic stimulation normalizes aberrant spike-LFP phase coupling in the hippocampal dentate gyrus and improves performance on cognitive tasks. The findings are preliminary and limited to a single-arm animal model without controlled comparison groups; translation to clinical utility remains speculative.
In vivo electrophysiology study with single-arm intervention in transgenic mouse model. 5XFAD transgenic mice (Alzheimer's disease model) and wild-type sham controls; specific age and sex not stated; recording site: hippocampal dentate gyrus.. Intervention: 40 Hz repetitive transcranial magnetic stimulation (rTMS) administered for 14 consecutive days. Compared with: 5XFAD mice baseline (pre-treatment) and wild-type sham controls.
5XFAD mice displayed reduced spike-LFP coupling compared to wild-type controls: mean vector length decreased by 19.90% (spike-θ) and 23.8% (spike-Hγ) Following 14 consecutive days of 40 Hz rTMS, 5XFAD mice showed significant increases in mean vector length: θ +39.44%; Hγ +31.47% rTMS treatment normalized spike-LFP phase distributions and markedly rescued learning, memory, and cognitive flexibility
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This work provides preclinical rationale for investigating 40 Hz rTMS as a potential disease-modifying approach in Alzheimer's disease, but results cannot yet inform clinical practice. Human trials would be needed to establish safety, tolerability, and efficacy in patients.
First in vivo characterization of spike-LFP coupling in AD model with single-arm intervention study; mechanistic findings in transgenic mice require confirmation in larger, controlled trials before clinical translation.
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This work provides preclinical rationale for investigating 40 Hz rTMS as a potential disease-modifying approach in Alzheimer's disease, but results cannot yet inform clinical practice. Human trials would be needed to establish safety, tolerability, and efficacy in patients.
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Objective. Spike-local field potential (LFP) coupling plays a pivotal role in mediating cross-scale neural communication. Although abnormal coupling has been reported in Alzheimer's disease (AD) models in vitro, in vivo evidence remains lacking. This study aimed to characterize in vivo spike-LFP coupling in 5XFAD mice and investigate whether 40 Hz repetitive transcranial magnetic stimulation (rTMS) can ameliorate related deficits.Methods. We performed chronic in vivo electrophysiological recordings of spikes and LFPs were performed in the hippocampal dentate gyrus (DG) via. Phase-locking and coherence analysis were employed to quantify spike-LFP coupling. Cognitive function was evaluated using the Y-maze, novel object recognition, and Morris water maze tasks. The correlation between spike-LFP coupling and cognitive performance was analyzed by the Spearman method.Results. In wild-type (WT) sham mice, DG spikes exhibited tightly confined phase preferences (θ oscillation: 108°-126°; high γ (Hγ) oscillation: 198°-216°). In contrast, 5XFAD mice displayed severely dispersed spike-phase distributions and reduced coupling intensity, with mean vector length decreasing by 19.90% (spike-θ) and 23.8% (spike-Hγ) compared with that in WT-sham controls. Following 14 consecutive days of 40 Hz rTMS intervention, 5XFAD mice exhibited significant increases in mean vector length (θ: +39.44%; Hγ: +31.47%) and normalized spike-LFP phase distributions. Notably, rTMS treatment also markedly rescued learning, memory, and cognitive flexibility in 5XFAD mice. Spike-LFP coupling strength was significantly correlated with learning and memory performance.Conclusion. These preliminary findings suggest that 40 Hz rTMS modulates pathological spike-LFP coupling in 5XFAD mice, laying the groundwork for therapeutic exploration.
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