This project will investigate the neural mechanisms and clinical antecedents underlying listening difficulty (LiD)
in school-age children born very preterm using a prospective cohort design. The long-term goal is to enhance
auditory and language outcomes for at-risk children. The central hypothesis is that extended high-frequency
(EHF) hearing loss stemming from exposures like ototoxic medications disrupts the integration of spatial and
talker cues during competing speech processing, thereby being a mechanism underlying LiD in preterm
children. The project will leverage an existing cohort of over 300 very preterm infants with prospectively
collected perinatal and neonatal clinical data, including audiological, behavioral, and neuroimaging results.
Antecedent factors of LiD and EHF hearing loss will be determined by testing associations between neonatal
clinical variables (e.g., ototoxic medication exposure, abnormal MRI at term, social risk factors) and later
emergence of LiD and EHF hearing loss. Identifying early clinical antecedents will allow targeted monitoring of
high-risk infants and guide neuroprotective management in the NICU to mitigate exposures leading to
impairments. A subset of 115 preterm children and 35 controls aged 6-8 years will undergo questionnaires,
audiological testing (including EHF thresholds), and neuropsychological assessments. EHF hearing loss will be
defined as >20 dB HL from 10-16 kHz. Listening difficulty will be quantified using the Evaluation of Children’s
Listening and Processing Skills (ECLiPS) caregiver questionnaire. A subset of 35 preterm children and 35
controls will also undergo magnetoencephalography (MEG) during a competing speech paradigm manipulating
talker and spatial cues. Neural tracking of the speech envelope will be evaluated using inter-event phase
coherence. The specific aims are: 1) Evaluate neural mechanisms underlying LiD in preterm children and 2)
Determine clinical antecedents of LiD and EHF hearing loss in preterm children. The hypotheses are: 1a) EHF
hearing loss will be associated with greater listening difficulty, 1b) EHF hearing loss will disrupt the integration
of spatial and talker cues as evidenced by reduced synergistic effects on neural speech tracking, 2a)
Antecedents of LiD will include abnormal MRI at term and high social risk status, and 2b) Antecedents of EHF
hearing loss will include ototoxic medication exposure and otitis media history. Linear regression models will
evaluate associations between EHF hearing loss and ECLiPS scores. Mixed effects models will test for
interactions between EHF hearing loss, spatial cues, and talker cues on neural tracking. Clinical antecedents
of EHF hearing loss and LiD will also be determined using regression models. By clarifying the neural
mechanisms and clinical antecedents of LiD in preterm children, this project will lay the groundwork for
developing targeted therapeutic interventions and early identification of high-risk children.
