{
  "id": 12938204,
  "title": "Self-Exciting Population Event Models Reveal Abnormal Temporal Amplification in MAPT-Mutant Human Brain Assembloids",
  "url": "https://urgent.news/2026/10/08/self-exciting-population-event-models-reveal-abnormal-temporal",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-08T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756068v1?rss=1"
  },
  "original_language": "en",
  "account": "Human brain assembloids serve as a useful tool for investigating mutation-specific network dysfunction, yet most studies fail to differentiate between abnormal activity originating from heightened spontaneous initiation or amplified history-dependent activity. Researchers have developed a simplified discrete-time self-exciting population model to analyze calcium-imaging event sequences, which isolates three key parameters: baseline initiation (%[mu]), integrated history-dependent gain (%[eta]), and memory decay (%[tau]).\n\nAnalysis of 175 recordings from 13 MAPT p.R406W mutant or CRISPR-corrected isogenic assembloids revealed a four-fold increase in the history-dependent gain parameter (%[eta]) in the mutant samples (95% confidence interval: 3.20- 5.84; exact p=7.8x10-4), without any rise in baseline activity. Further examination showed the presence of residual Poisson overdispersion, but even with fixed-decay and beta-binomial sensitivity analyses, the mutant history effect remained intact.\n\nThe median history-dependent gain parameter (%[eta]) effectively distinguished between all 13 held-out assembloids, and a multifeature recording-level RBF-SVM achieved an area under the curve of 0.816 when evaluated on nested whole-assembloid holdout data. These findings demonstrate that robust history-dependent temporal amplification is a functional phenotype of MAPT-mutant networks.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}