Uncovering the Neural Mechanisms and Antecedent Factors of Listening Difficulty in Preterm Children

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.