Computational model for synthesizing auditory brainstem responses to assess neuronal alterations in aging and autistic animal models

Abstract

PurposeThe 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. MethodThis 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 of these conditions, these ABR alterations are caused by known distinct changes in auditory brainstem physiology, and the model could recapitulate these changes. ResultsIn 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. For the aging condition, 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. ConclusionThese results demonstrate not only the models accuracy but also its capability of linking features of ABR morphology to underlying neuronal properties and suggesting follow-up physiological experiments.