# Brainstem Arousal Network in Human Consciousness: Healthy development vs SIDS

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $725,598

## Abstract

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality in industrialized
nations today. Typically it occurs during a sleep period – unwitnessed, it is presumed to occur during sleep
itself, or during one of the many transitions between sleep and waking that occur during normal infant sleep. A
leading hypothesis today is the arousal deficit hypothesis: SIDS, or a subset of SIDS, is due to a failure in the
ascending arousal network (AAN) to a life-threatening stressor during sleep in a critical developmental period.
Arousal is considered an essential element of consciousness, as well as essential for restoration of
homeostasis during respiratory and cardiovascular challenges by providing excitatory drive to vital processes
from sleep. The AAN is interconnected with cortical and subcortical networks that regulate the integration of
homeostatic responses, comprised of connectivity with brainstem and limbic nodes. Our laboratory has
provided evidence over the last two decades that serotonin (5-HT) defects are concentrated mainly in a
cytologically defined region of the rostral medullary reticular formation in the AAN of the brainstem which we
call the putative "core lesions of SIDS" (CLS). In this R01 application, we propose to test the two-fold
hypothesis that the core nuclei in the CLS have fiber interconnections with each other and with one or more
known nuclei of the AAN within and above the brainstem, thereby demonstrating they are anatomically part of
the AAN; and that there are structural anatomic abnormalities in the serotonergic CLS in the SIDS cases
compared to the age-matched autopsy controls. We will perform ex vivo MRI with diffusion tractography and
optical coherence tomography at unprecedented spatial resolution along with 5-HT immunocytochemistry in
postmortem infant brains from birth to the end of the first year of life, the period of risk for SIDS. This work is
expected to have a significant positive impact. By establishing the putative core CLS as an integral part of the
AAN involving medullary 5-HT neurons, it will provide the foundation for targeted future brain research in SIDS,
bringing us closer to the ultimate cause(s) of SIDS and specific preventive strategies.

## Key facts

- **NIH application ID:** 10209378
- **Project number:** 1R01HD102616-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lilla Zollei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $725,598
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209378

## Citation

> US National Institutes of Health, RePORTER application 10209378, Brainstem Arousal Network in Human Consciousness: Healthy development vs SIDS (1R01HD102616-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10209378. Licensed CC0.

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