Developing a Biomarker for Infant Speech Perception in Children with Hearing Loss

 描述(由申请人提供)：这份K23申请的主要主题是开发一个研究计划，目的是改善听力损失儿童的结果，并进一步发展我作为临床医生兼科学家的职业生涯。为了发展作为一名临床科学家的职业生涯，我们与我的导师们一起开发了一个包括三个目标的培训计划：1)利用诱发电位反应来开发婴儿言语识别的生物标记物，2)学习技术以建立预测有效性，以及3)深入培训I纵向统计分析。这一培训将通过导师指导、教学课程工作和研究项目来完成。这项研究项目是由于听力损失儿童的言语和语言结果有相当大的差异而发展起来的。虽然自新生儿听力筛查开始以来已经取得了许多进展，但仍有大量工作需要做，以最佳地适应听力损失婴儿的放大，缩小听力正常儿童和重听儿童之间在听力和口语能力方面的差距。行为技术，如条件转头，可以用来评估婴儿的言语辨别能力。然而，这些技术受到最低年龄限制和对大量继发性残疾婴儿的不切实际的限制。 婴儿言语歧视生物标志物的开发将对每年1000名永久性听力损失婴儿中的3名产生重大影响。作为第一步，这项应用寻求验证婴儿语音感知的生物标记物，该标记物可以在匹配放大后不久进行测量。被称为失配反应/负波(MMR/N)的事件相关电位是建议的生物标记物。在过去的一年里，试点数据收集使我们能够获得14名听力正常(NH)婴儿和两名听力损失(HL)婴儿的可靠数据。这些方法需要在更大的人群中进行验证。将对刺激类型(语音和非语音)进行进一步验证，并评估分析类型(信号平均与主成分分析)在听力正常和听力障碍婴儿中的可靠性和敏感性。这些孩子将被纵向跟踪。在2个月时参加MMR/N的同一组儿童将在7个月后再次接受检查，以使用一种名为视觉强化婴儿言语辨别(VRISD)的条件转头技术对他们的言语感知进行行为检查。参加MMR/N和VRISD方案的儿童在16、24、27和30个月时，将对语言结果进行评估。这一设计将允许检查MMR/N与行为言语知觉以及随时间跟踪的后来的语言能力的关系，以确定MMR/NS作为言语知觉能力的生物标记的有效性。这项拟议的研究将推进听力损失婴儿的MMR/N方法，并确定MMR/N是否可用于衡量这一人群的言语辨别能力。这项建议的中心假设是，可以使用非侵入性语音诱发听觉电位MMR/N来确定放大的语音信号是否能为2个月大的听力丧失的婴儿提供足够的听力 在16、24、27和30个月时的语言能力与2个月时的MMR/N之间存在关系。K23资助机制提供的研究培训将使我能够扩大我在听觉诱发电位方面的知识基础，作为生物标记物开发的模型，学习建立两种不同措施之间有效性的新方法，包括纵向跟踪，以及发展一条独立的研究路线。这项研究和培训计划的最终目标是为PI的职业生涯做好准备，成为一名可持续资助的临床科学家，专注于将婴儿言语感知机制与基于证据的临床实践联系起来的翻译研究的必要性。

 DESCRIPTION (provided by applicant): The overarching theme of this K23 application is to develop a research program with the aim of improving outcomes for children with hearing loss and to further my career as a clinician-scientist. In order to develop a career as a clinician scientist, together with my mentors, we have developed a training program that includes three goals: 1) utilizing evoked potential responses to develop a biomarker of infant speech discrimination, 2) learning techniques to establish predictive validity, and 3) in-depth training i longitudinal statistical analysis. This training will be accomplished through mentorship, didactic course work, and a research project. This research project was developed due to the considerable variation in speech and language outcomes in children with hearing loss. While many gains have been made since the beginning of newborn hearing screenings, there is still significant work that needs to be done to optimally fit amplification in infants with hearing loss,to decrease the gap in listening and spoken language abilities between normal hearing and hard- of-hearing children. Behavioral techniques such as a conditioned head turn are available to assess speech discrimination in infants. These techniques, however, are limited both by a minimum age limit and by impracticality for the large group of infants with secondary disabilities. The development of a biomarker for infant speech discrimination would significantly impact the 3 out of 1000 infants per year identified with permanent hearing loss. As a first step, this application seeks to validate a biomarker of infant speech perception that can be measured shortly after the fitting of amplification. The event-related potential known as the mismatch response/negativity (MMR/N) is the proposed biomarker. Pilot data collection over the past year has allowed us to obtain reliable data in 14 normal hearing (NH) infants and two infants with hearing loss (HL). These methods need to be validated in a larger population. Further validation will be done for the stimulus type (speech and non-speech) and to assess the reliability and sensitivity of analysis type (signal averaging vs. principal component analysis) in normal hearing and hard-of-hearing infants. These children will be followed longitudinally. The same children who participated in MMR/N at 2 months will be seen again at 7 months to have their speech perception examined behaviorally using a conditioned head turn technique known as visually reinforcement infant speech discrimination (VRISD). Language outcomes will be assessed in the same children who participated in the MMR/N and VRISD protocols when they are 16, 24, 27, and 30 months. This design will allow examination of the relationship of MMR/N with behavioral speech perception and later language abilities tracked over time to determine MMR/Ns validity as a biomarker for speech perception abilities. The proposed research will advance MMR/N approaches in infants with hearing loss and determine if MMR/N can be used as a measure of speech discrimination in this population. The central hypothesis of this proposal is that a non-invasive speech-evoked auditory potential, MMR/N, can be used to determine if the amplified speech signal provides sufficient audibility for babies with hearing loss at 2 months of age to discriminate between two different speech sounds and there will be a relationship between language abilities at 16, 24, 27, and 30 months of age and MMR/N at 2 months. The research training provided by the K23 funding mechanism will allow me to widen my knowledge base in auditory evoked potentials as a model for biomarker development, learn new approaches to establishing validity between two different measures, including longitudinal follow-up, as well as develop an independent line of research. The ultimate goal of this research and training program is to prepare the PI for a career as a sustainably funded clinician-scientist who focuses on the need for translational research linking mechanisms of infant speech perception to evidence based clinical practice.