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Changes in EEG Complexity Following Trazodone Administration in a Mouse Model of Alzheimer’s Disease

Poster Session F - Tuesday, March 10, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Emad Shams^1,2, Kelly Shen¹, Mayuko Arai³, Cody Stevens², Jefferey Yue², Randy McIntosh^1,2, Brianne Kent^1,2; ¹Institute for Neuroscience and Neurotechnology, Simon Fraser University, ²Simon Fraser University, ³Centre for Neuroscience, University of California Davis

Neural complexity, an indicator of information processing capacity in brain networks, is associated with cognitive function and can be indexed formally by measures of entropy of brain signals. Here, we evaluate changes in neural complexity to assess treatment effectiveness in a mouse model of Alzheimer’s disease (AD). Trazodone is an antidepressant being explored as a novel therapeutic for AD, with beneficial effects on sleep and cognition demonstrated in both humans and mouse models of disease. Trazodone’s effect on neural complexity has not been studied to our knowledge.    We administered trazodone (60mg/kg) to the APPNL-F transgenic mouse model at 9 months (nTotal=12, nTreatment=6) or 14 months (nTotal=15, nTreatment=10) of age for 60 days. Intracranially implanted EEG was recorded at baseline and every ~15 days during the 60 days of treatment.  Vigilance state was scored using Sirenia Sleep software (Pinnacle) and multiscale entropy (MSE) was computed using a custom MATLAB function.   To assess whether trazodone alters brain signal complexity, we used mean-centered partial least squares (PLS) analysis. The first pattern from PLS revealed significant treatment effects across both cohorts, with trazodone increasing complexity at finer temporal scales and decreasing complexity at coarser scales. This effect was significant across all vigilance stages for both cohorts.  Our results demonstrate that trazodone alters brain signal complexity as measured by MSE. The MSE curve morphology in the trazodone group resembles that of healthy aging, suggesting a beneficial effect. 

Topic Area: METHODS: Electrophysiology