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Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision.

Overview

Authors: Danielle Barda1, Lior Dor2,3, Hila Sapir2, Shaked Weinberger1, Yuval Avni Mann1, Aviv Or-Zeid1, Netta Baram2, Dror Lederman4, Hava Golan1,3, Jennifer Resnik2,3
ORCID iDs: Lior Dor, Hava Golan
  1. Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, 84105 Israel
  2. Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, 84105 Israel
  3. Zelman Center for Brain Science Research, Ben-Gurion University of the Negev, Beer Sheva, 84105 Israel
  4. Faculty of Engineering, Holon Institute of Technology, Holon, 5810201 Israel
Journal: Journal of neurodevelopmental disorders, volume 18, issue 1, article 29
Dates: received 6 January 2026; accepted 1 April 2026; published online 10 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s11689-026-09692-2 · PMID 41963776 · PMCID PMC13191893 · OpenAlex W7153045921
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: optical imaging (calcium, voltage, 2-photon) (modality), human (organism), mouse (organism), other condition (population)
Methods: Statistics, Machine learning, Preprocessing, Spectral & time-frequency, Single-unit activity, calcium imaging
MeSH: Auditory Cortex*, Auditory Perception*, Evoked Potentials, Auditory, Brain Stem*, Folic Acid*, Methylenetetrahydrofolate Reductase (NADPH2)*, Vocalization, Animal*, Acoustic Stimulation, Animals, Animals, Newborn, Auditory Acuity, Female, Male, Mice, Mice, Knockout (* major topic)
Topic: Hearing, Cochlea, Tinnitus, Genetics (Sensory Systems, Neuroscience), according to OpenAlex
Funding: Israel Science Foundation (515/17, 725/21)
Citations: not cited yet (Europe PMC); 37 references in the paper

Abstract

Methylenetetrahydrofolate‐reductase (MTHFR) is a critical enzyme in folate-dependent one-carbon metabolism. While MTHFR polymorphisms have been linked to sensorineural hearing loss and neurodevelopmental disorders in humans, the translation of early-life metabolic stress into long-term sensory processing and perceptual consequences has remained unclear. Here, we combined neonatal ultrasonic vocalization analysis, adult auditory-brainstem recordings, two-photon calcium imaging of the auditory cortex, and high-resolution psychophysics to map the effects of partial Mthfr deficiency across different developmental stages. MTHFR-deficient pups produced calls with lower onset frequencies and altered temporal structure. In adulthood, MTHFR-deficient mice exhibited elevated auditory brainstem response thresholds and reduced wave I amplitudes, indicating reduced cochlear output. Despite robust cortical tone responses, two-photon imaging revealed significantly broadened frequency–response areas, and a trained cortical activity decoder showed selectively reduced separability for closely spaced tones. Guided by these neural findings, behavioral testing revealed intact discrimination for widely separated tones but impaired performance near the perceptual boundary, indicating reduced fine spectral acuity. Together, these findings outline a developmental trajectory in which early metabolic stress impairs peripheral encoding, central gain compensates for the loss of sensitivity, and perceptual precision is ultimately compromised, highlighting one-carbon dysregulation as a modifiable contributor to auditory dysfunction.

Supplementary Information: The online version contains supplementary material available at 10.1186/s11689-026-09692-2.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability

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Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 14 MeSH terms, 1 funder, 37 references.

Cite

This paper

Barda, D., Dor, L., Sapir, H., Weinberger, S., Mann, Y. A., Or-Zeid, A., Baram, N., Lederman, D., Golan, H., & Resnik, J. (2026). Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision. Journal of neurodevelopmental disorders, 18(1), 29. https://doi.org/10.1186/s11689-026-09692-2

BibTeX

@article{barda2026altered,
author = {Barda, Danielle and Dor, Lior and Sapir, Hila and Weinberger, Shaked and Mann, Yuval Avni and Or-Zeid, Aviv and Baram, Netta and Lederman, Dror and Golan, Hava and Resnik, Jennifer},
title = {{Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision}},
journal = {Journal of neurodevelopmental disorders},
year = {2026},
month = apr,
volume = {18},
number = {1},
pages = {29},
publisher = {BMC},
issn = {1866-1947},
doi = {10.1186/s11689-026-09692-2},
url = {https://doi.org/10.1186/s11689-026-09692-2},
pmid = {41963776},
pmcid = {PMC13191893}
}

RIS

TY - JOUR
AU - Barda, Danielle
AU - Dor, Lior
AU - Sapir, Hila
AU - Weinberger, Shaked
AU - Mann, Yuval Avni
AU - Or-Zeid, Aviv
AU - Baram, Netta
AU - Lederman, Dror
AU - Golan, Hava
AU - Resnik, Jennifer
TI - Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision
T2 - Journal of neurodevelopmental disorders
J2 - J Neurodev Disord
PY - 2026
DA - 2026/04/10
VL - 18
IS - 1
SP - 29
SN - 1866-1947
PB - BMC
DO - 10.1186/s11689-026-09692-2
UR - https://doi.org/10.1186/s11689-026-09692-2
LA - en
ER -

CSL-JSON

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