# Neuroimaging Studies in Pediatric Anesthesia Neurotoxicity

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $651,818

## Abstract

PROJECT SUMMARY/ABSTRACT
Millions of young children are exposed to general anesthesia each year. Exposure of young animals to
anesthesia can cause neurodegenerative changes with adverse effects on learning and behavior. The
concern generated by these observations is highlighted by the recent FDA issuance of a Drug Safety
Communication warning that general anesthesia and sedation drugs used in children < 3 years of age who
were undergoing prolonged or repeated exposures “may affect the development of children’s brains.” In prior
work, we studied the association between anesthesia exposure prior to age 3 and neurodevelopmental
phenotype, as assessed by a detailed neuropsychological assessment of 997 children sampled from a
propensity-matched, population-based birth cohort (children born in Olmsted County, MN from 1994-2007).
Children exposed to multiple anesthetics had consistent deficits in cognitive processing speed and fine motor
skills, without significant deficits in other domains including general intelligence, memory, and executive
function. These deficits were associated with behavioral problems and learning difficulties as reported by
parents, including an increased frequency of attention-deficit/hyperactivity disorder (ADHD) and learning
disabilities. Conditions such as ADHD are associated with structural and functional brain abnormalities in
children as revealed by MRI scans We performed preliminary imaging studies in the children tested in the prior
studies and found that children multiply-exposed to anesthesia also demonstrate consistent neuroanatomical
changes. The central hypothesis of this proposal is that exposure to anesthesia prior to age 3 is associated
with specific structural and functional changes in the brain as assessed by MRI. The Specific Aim of this
proposal is to determine if the neurodevelopmental abnormalities of these children are associated with specific
changes in brain MRIs. To accomplish this aim, children will be recruited from among those Olmsted County
children already phenotyped in our prior work, based on anesthesia exposure history (100 each of unexposed,
singly-, and multiply-exposed children). Their brains will be imaged in a novel 3T MRI scanner, with a protocol
including 3-D T1-weighted and T2-weighted anatomic sequences, resting-state functional MRI, and diffusion
tensor imaging. We will determine the relationship between MRI findings, anesthesia exposure, and
neurocognitive findings to evaluate the hypothesis that brain imaging measurements mediate the association
of anesthesia exposure with neurocognitive outcomes. The expected product of this research could be the first
biomarker for anesthesia-associated neural injury in children. Consistent imaging changes (as suggested by
our preliminary data), despite the considerable variation between children regarding factors such as type of
procedure and socioeconomic status, could provide important insights into potential mechanisms responsible
for injury.

## Key facts

- **NIH application ID:** 10357925
- **Project number:** 5R01HD099147-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** David O. Warner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $651,818
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357925

## Citation

> US National Institutes of Health, RePORTER application 10357925, Neuroimaging Studies in Pediatric Anesthesia Neurotoxicity (5R01HD099147-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357925. Licensed CC0.

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