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Using The Virtual Brain to probe the effects of senescence-driven alterations in neuronal firing activity on brain dynamics in Alzheimer’s disease

Poster Session A - Saturday, March 7, 2026, 3:00 – 5:00 pm PST, Fairview/Kitsilano Ballrooms

Cathlin Jiaqi Han¹ (cjh26@sfu.ca), Alex I. Wiesman¹, Anthony Randal McIntosh¹; ¹Simon Fraser University

Cellular senescence is a distinctive change in cell state that is characterized by permanent cell cycle arrest and dramatic phenotypic changes. The senescence of neurons, termed neuronal senescence (NS), displays intimate associations with the pathology of Alzheimer’s disease (AD) and is proposed to contribute to its development and progression. Critically, recent in vitro findings reveal that the induction of senescence in neurons significantly reduces their spontaneous firing rate (SFR) – suggesting a direct mechanism by which NS may contribute to altered brain dynamics in AD. Challenges in studying NS in vivo have however limited further investigation of this proposed mechanism, leaving its consequences on AD brain dynamics unclear. This study proposes a multiscale computational modelling approach to address these gaps. Specifically, it is hypothesized here that these NS-driven SFR changes will affect local excitation-inhibition balance and, consequently, result in altered brain dynamics seen in AD, such as neural slowing and functional connectivity changes. To probe this hypothesis, the brain simulation platform The Virtual Brain will be used to launch corresponding simulations both at the local, neural circuit level and the large-scale, whole-cortex level. In doing so, this approach is expected to provide novel insight into the yet examined consequences of NS-driven SFR changes on AD brain dynamics. In addition to informing on NS and its involvement in AD, the multiscale modelling approach proposed here will address growing interest in efforts to bridge insights across the field of AD research to produce more integrated and unified models of AD.

Topic Area: OTHER