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Purpose <p>The auditory brainstem response (ABR) is a widely used objective electrophysiology measure for non-invasively assessing auditory function and neural activity in the auditory brainstem, but its ability to reflect detailed neuronal processing is limited due to the averaging nature of the electroencephalogram-type recordings.</p> Method <p>This study addresses this limitation by developing a computational model of the auditory brainstem, which is capable of synthesizing ABR traces based on a large, population scale neural extrapolation of a spiking neuronal network of auditory brainstem circuitry. The model was able to recapitulate alterations in ABR waveform morphology that have been shown to be present in two medical conditions: animal models of autism and aging. Moreover, in both conditions, the ABR alterations are caused by known, distinct changes in auditory brainstem physiology, and the model could recapitulate these changes.</p> Results <p>In the autism model, the simulation revealed myelin deficits and hyperexcitability, which caused a decreased wave III amplitude and a prolonged wave III-V interval, consistent with experimentally recorded ABRs in <i>Fmr1</i>-KO mice (<i>Fmr1</i>-KO: <i>N</i> = 19, 9 females; B6: <i>N</i> = 10, 3 females). For the aging condition (old: <i>N</i> = 23, 11 females, P750 to P1167; young: <i>N</i> = 39, 13 females, P60 to P109), the model recapitulated ABRs recorded in aged gerbils and indicated a reduction in activity in the medial nucleus of the trapezoid body (MNTB), a finding validated by confocal imaging data.</p> Conclusion <p>These results demonstrate not only the model’s accuracy but also its ability to link features of ABR morphology with underlying neuronal properties and suggest follow-up physiological experiments.</p>

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Computational Model for Synthesizing Auditory Brainstem Responses to Assess Neuronal Alterations in Aging and Autistic Animal Models

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Ben-Zheng Li,
  • Shani Poleg,
  • Matthew Ridenour,
  • Daniel Tollin,
  • Tim Lei,
  • Achim Klug

摘要

Purpose

The auditory brainstem response (ABR) is a widely used objective electrophysiology measure for non-invasively assessing auditory function and neural activity in the auditory brainstem, but its ability to reflect detailed neuronal processing is limited due to the averaging nature of the electroencephalogram-type recordings.

Method

This study addresses this limitation by developing a computational model of the auditory brainstem, which is capable of synthesizing ABR traces based on a large, population scale neural extrapolation of a spiking neuronal network of auditory brainstem circuitry. The model was able to recapitulate alterations in ABR waveform morphology that have been shown to be present in two medical conditions: animal models of autism and aging. Moreover, in both conditions, the ABR alterations are caused by known, distinct changes in auditory brainstem physiology, and the model could recapitulate these changes.

Results

In the autism model, the simulation revealed myelin deficits and hyperexcitability, which caused a decreased wave III amplitude and a prolonged wave III-V interval, consistent with experimentally recorded ABRs in Fmr1-KO mice (Fmr1-KO: N = 19, 9 females; B6: N = 10, 3 females). For the aging condition (old: N = 23, 11 females, P750 to P1167; young: N = 39, 13 females, P60 to P109), the model recapitulated ABRs recorded in aged gerbils and indicated a reduction in activity in the medial nucleus of the trapezoid body (MNTB), a finding validated by confocal imaging data.

Conclusion

These results demonstrate not only the model’s accuracy but also its ability to link features of ABR morphology with underlying neuronal properties and suggest follow-up physiological experiments.