# Dissecting arousal impact on sensory processing in Rett Syndrome

> **NIH NIH P50** · BOSTON CHILDREN'S HOSPITAL · 2021 · $165,750

## Abstract

ABSTRACT
Rett Syndrome (RTT) is a rare X-linked developmental brain disorder due to de novo pathogenic variants in
MECP2 and mainly affecting girls. Notably, RTT individuals reach typical developmental milestones in the first
6-18 months of life, followed by stagnation and then regression of acquired skills. The severe cognitive delays,
deficits in sensory processing and dysregulated behavioral states profoundly impact both patient and family
quality of life. We still do not know when and how autonomic and central brain networks begin to derail from the
neurotypical developmental trajectory, nor we have effective treatments targeting these impairments. Hence,
there is an urgent need for objective, quantitative, non-invasive, and translational biomarkers for early
assessment of cognition and behavioral states in RTT, their progression over time and response to therapeutic
interventions. Our goals are to establish 1) spontaneous pupil and heart rate (HR) fluctuations as new biomarkers
for RTT, 2) how arousal impacts the progression of RTT cortical pathophysiology and 3) develop targeted
interventions. We will address these challenges using a multi-level circuit approach both in RTT girls and awake
Mecp2 female heterozygote mice during the progression of the disorder. The proposed work will refine and
establish spontaneous pupil and HR fluctuations as highly translational biomarkers to track autonomic nervous
system function, while dissecting how and when neuromodulation impacts sensory processes in RTT. Together
these approaches will allow the development of new circuit-based therapies in patients. Our results will be pave
the way to future studies of RTT related disorders such as MECP2 duplication, CDKL5 deficiency disorder and
FOXG1 syndrome.

## Key facts

- **NIH application ID:** 10239469
- **Project number:** 1P50HD105351-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Michela Fagiolini
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,750
- **Award type:** 1
- **Project period:** 2021-07-22 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239469

## Citation

> US National Institutes of Health, RePORTER application 10239469, Dissecting arousal impact on sensory processing in Rett Syndrome (1P50HD105351-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10239469. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*