Self-Exciting Population Event Models Reveal Abnormal Temporal Amplification in MAPT-Mutant Human Brain Assembloids
- 1Carnegie Mellon University
Abstract
Human brain assembloids provide a tractable platform for studying mutation-specific network dysfunction, but most studies do not distinguish whether abnormal activity arises from increased spontaneous initiation or stronger history-dependent amplification. We introduce a low-dimensional discrete-time self-exciting population model for calcium-imaging event sequences that separates baseline initiation (%[mu]), integrated history-dependent gain (%[eta]), and memory decay (%[tau]). Across 175 recordings from 13 MAPT p.R406W or CRISPR-corrected isogenic assembloids, biological-unit inference identified a 4.31-fold increase in %[eta] in mutants (95% CI 3.20- 5.84; exact p=7.8x10-4), without increased baseline activity. Parametric predictive checks exposed residual Poisson overdispersion; fixed-decay and beta-binomial sensitivity analyses nevertheless preserved the mutant history effect. Median %[eta] separated all 13 held-out assembloids, while a multifeature recording-level RBF-SVM achieved AUC 0.816 under nested whole-assembloid holdout. These results identify robust history-dependent temporal amplification as a functional MAPT-mutant network phenotype.
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BibTeX
@misc{monsoor2026selfexciting,
title = {{Self-Exciting Population Event Models Reveal Abnormal Temporal Amplification in MAPT-Mutant Human Brain Assembloids}},
author = {T. Monsoor and C. M. McCrimmon and P. Sinha and L. Zhang and M. R. Dareddy and M. E. Lorasdagi and R. A. Samarasinghe and V. Roychowdhury},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756068},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756068v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Self-Exciting Population Event Models Reveal Abnormal Temporal Amplification in MAPT-Mutant Human Brain Assembloids
AU - T. Monsoor
AU - C. M. McCrimmon
AU - P. Sinha
AU - L. Zhang
AU - M. R. Dareddy
AU - M. E. Lorasdagi
AU - R. A. Samarasinghe
AU - V. Roychowdhury
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.756068
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.756068v1
AB - Human brain assembloids provide a tractable platform for studying mutation-specific network dysfunction, but most studies do not distinguish whether abnormal activity arises from increased spontaneous initiation or stronger history-dependent amplification. We introduce a low-dimensional discrete-time self-exciting population model for calcium-imaging event sequences that separates baseline initiation (%[mu]), integrated history-dependent gain (%[eta]), and memory decay (%[tau]). Across 175 recordings from 13 MAPT p.R406W or CRISPR-corrected isogenic assembloids, biological-unit inference identified a 4.31-fold increase in %[eta] in mutants (95% CI 3.20- 5.84; exact p=7.8x10-4), without increased baseline activity. Parametric predictive checks exposed residual Poisson overdispersion; fixed-decay and beta-binomial sensitivity analyses nevertheless preserved the mutant history effect. Median %[eta] separated all 13 held-out assembloids, while a multifeature recording-level RBF-SVM achieved AUC 0.816 under nested whole-assembloid holdout. These results identify robust history-dependent temporal amplification as a functional MAPT-mutant network phenotype.
ER -