Patrick C.M. Wong - US grants

[unreadable] DESCRIPTION (provided by applicant): Auditory Processing Disorders (APD), also known as Central Auditory Processing Disorders, is characterized by deficits in processing complex verbal and nonverbal acoustic signals. The diagnosis, treatment, and even the very existence of APD are controversial. Little is known about the pathophysiology of APD. The National Institute of Deafness and Other Communication Disorders stated that much research is still needed to understand this disorder (NIH Pub. No. 01-4949, 2004). Despite the lack of evidence on many fronts, as well as difficulty with third-party payment reimbursements, individuals with APD symptoms are being diagnosed and treated everyday, and students in clinical audiology are taught to provide services to this population. This proposed research aims at building evidence for APD, with particular attention to exploring the common belief that APD is associated with neurophysiologic and possibly neuroanatomic anomalies in the central auditory nervous system. Functional Magnetic Resonance Imaging will be utilized as APD individuals process complex acoustic signals, as well as high-resolution anatomical imaging. Although APD is often discussed in children, this first research will focus on the more ontogenetically developed brain (ages 25 to 40) for ease of comparison with existing auditory fMRI data. Future experiments will include both children and adults. Specifically, the proposed research aims at investigating the following: 1) Whether neuroanatomic anomalies exist in adults diagnosed with APD based on behavioral testing, and whether it is feasible to use MRI to identify them. 2) Whether it is feasible to use MRI to identify neurophysiologic anomalies in APD adults. If so, whether APD is associated with a collection of unifying or diverse neurophysiologic anomalies. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): This is a cross-sectional study examining behavioral and neurophysiologic changes associated with learning Mandarin Chinese as a second language (L2) by native English-speaking adult learners (ages 18 years and up). It will focus on the acquisition of lexical tones, which are pitch patterns that are used to contrast word meaning in Mandarin, and is not a linguistic feature of English. At the behavioral level, various studies investigating the learning of isolated non-native consonants in non-lexical and non-communicative contexts show that with the appropriate form and degree of training, adults can learn to perceive and/or produce sounds that do not occur in their native language. However, there have been few studies that investigated the learning of lexical tones or suprasegmentals, and fewer yet that considered the use of these non-native sounds in actual communicative contexts such as words. In recent years, several studies examined neural changes associated with speech and word learning; but they are either confined to laboratory training of speech sounds, or the learning of words without considering the contribution of phonetic features, especially suprasegmentals. While cross-linguistic research has been done comparing behavioral and neurophysiologic responses of native Mandarin-speaking and native English-speaking adults perceiving Mandarin tones, none was conducted to describe changes in non-Mandarin (English) speaking subjects as they become proficient in Mandarin. The current study will involve behavioral and fMRI experiments on university students learning Mandarin Chinese at four different stages (years 1 to 4 of the university curriculum). The general hypothesis is that increased L2 proficiency will result in behavioral and neurophysiologic responses closer to those in native speakers. An understanding of language development is important for developing the most efficacious language rehabilitation programs in cases of injuries such as strokes. For the rehabilitation of adults, it is especially important to understand how adults learn. [unreadable] [unreadable] [unreadable]

The ability to produce and understand the intricacies of human speech has a large impact on quality of life. Auditory communication often involves learning; for example, identifying a new friend's voice over the telephone, perceiving and producing words in a foreign language, or understanding the meaning of words used in different contexts. The traditional view of the auditory system emphasizes a feed forward pathway starting from the inner ear in the cochlea, progressing to the various brainstem nuclei, the thalamus, and finally up to the auditory cortex. As acoustical and/or functional complexities of the auditory signal increase, the more likely ?higher-level? structures are to be involved. Although the existence of this corticofugal (descending) system is acknowledged in the literature, relatively little research, especially in terms of physiology, has been conducted. The functions of individual auditory-neural structures have been studied in isolation yet researchers lack an understanding of the simultaneous contributions of these structures in performing auditory functions in humans. With support from the National Science Foundation, Dr. Patrick Wong and his research team will explore whether learning speech (particularly the lexical tones of Mandarin) and music can result in changes in lower level circuitry, which could potentially then influence processing upstream that is associated with auditory encoding. Investigations on brain anatomy and physiology will be conducted using brainstem electrophysiologic and functional magnetic resonance imaging (fMRI) procedures at various time points in a training paradigm, in which participants will learn to use pitch patterns to identify English pseudo words. This study contributes to the ongoing effort to explore the plasticity of lower and higher level structures across different stages of learning, and how these functions may differ in successful and less successful learners.

This research will lead to a more comprehensive understanding of brain plasticity as it pertains to auditory learning. On a broader level, this research is directly relevant to music and foreign language instruction. Regarding clinical applications, this research may shed light on hearing-related disorders which occur throughout the auditory pathway (e.g., peripheral hearing loss and central processing disorders). Additionally, the research focuses on a type of language (tone language) that is spoken natively in many parts of the world. The topic of second language learning is also important to global competitiveness, and this research should lead to improvements in our understanding of the process of learning Mandarin tones.

DESCRIPTION (provided by applicant): Genetic factors, along with environmental factors such as long- and short-term experiences, shape the physiologic foundations for the acquisition of communicative behaviors. Although much research has been conducted on the genetic bases of peripheral hearing loss and craniofacial anomalies that result in speech production deficits, no research has focused on the genetic predispositions associated with success in language learning in adulthood. Such lack of research occurs in the context of a longstanding pattern of findings indicating large individual differences in language recovery, auditory training, and second language learning. The proposed research synergistically builds upon three independent lines of recent (within past 6 months) high- impact research developments, with the aim to produce transformative findings concerning the interactions among language learning, the brain, and genetic differences. These latest developments include: 1) the association between individual differences in language learning and neuroanatomic and neurophysiologic differences (Wong et al., 2007;Wong et al., in press);2) the genetic link to differences in language typology (Dediu &Ladd, 2007);and 3) the association between specific allelic variations and brain functions (Buckholtz et al., 2007;Gurling et al., 2007). Although possessing a significant risk, this research will form a foundation for proteomic studies examining protein expression patterns that are directly consequential to brain development that affects spoken language processing and learning, including rehabilitative/habilitative audiologic, and neurogenic language treatment paradigms. This research is not only particularly timely, but is also consistent with all priority areas stated in the latest NIDCD strategic plan (FY2006-2008). It will bring together investigators from two ends of the communication sciences discipline (molecular biology and cognitive neuroscience) for a lifelong collaboration on high-impact research of broad significance to clinical diagnosis and treatment. The specific aims are 1) to examine whether spoken language differences and the accompanying neural differences are associated with specific allelic variations;and 2) to examine whether such allelic variations are specific to one type or multiple types of spoken language learning. PUBLIC HEALTH RELEVANCE: Genetic and environmental factors affect our brain and its function including language communication. In an increasingly multi-lingual/multi-cultural world, many people, including adults, are interested in learning a foreign language even though it is difficult for them to do so. Our proposed research seeks to understand why some people can learn spoken language more successfully than others by examining genetic differences across learners.

DESCRIPTION (provided by applicant): The proposed research focuses on the behavioral and neurologic factors influencing spoken language (sound-to-word) learning, specifically the learning of non-native lexical tones and consonants in word identification in adulthood. Our behavioral-neural approach will enable the pursuit of our long-term goal of seeking the most desirable learning outcome mediated by behavioral training. The ten planned experiments in this grant application employ techniques that include behavioral training, neuroanatomic characterizations of learners of different learning abilities, and measurements of neurophysiologic (cerebral hemodynamic) changes associated with learning. The specific aims are to: 1) Compare the efficacy of non-native lexical tone and consonant training programs that emphasize low- versus high-stimulus variability in the training stimuli, and to compare neurophysiologic responses (measured by event-related fMRI) associated with the two training programs;2) Investigate whether poor lexical learning can be remediated by additional training that focuses on phonetic (non-lexical pitch and consonant) learning and to examine neurophysiologic changes associated with such remediation;and 3) Characterize neuroanatomic differences between learners of different abilities. Guided by our newly proposed model of spoken language processing and learning called the Integrated Spoken Language Acquisition Network, we hypothesize the following: 1) Training with high-stimulus variability is the most efficacious, which is indicated by increased brain responses in auditory association cortex and the recruitment of the parietal lobe;2) poor word learning resulting from a lack of phonetic representation and can be remediated by first training to establish such representations before word learning;and 3) poor learners can be identified by a relatively smaller left Heschl's Gyrus (driven by grey or white matter depending on the acoustic feature);however, successful learning can still be achieved with the appropriate remedial training. By understanding the efficacy of different training programs and how they benefit individuals of different learning profiles, as well as by identifying the neural characteristics of the different learners before and after training, we move a step closer to being able to place learners into training programs that are likely to be the most cost- effective and will likely lead to the most desirable learning outcomes. In an increasingly multi-lingual/multi-cultural world, many people, including adults, are interested in learning a foreign language even though it is difficult for them to do so. Learning a foreign language requires resources in our brain and changes occur as a result of learning. Our proposed research seeks to understand the changes that occur in the brain as adults learn to use foreign sounds in words, what effects different training methods have on the brain, and why certain individuals can learn more successfully (e.g., whether they have different brain organization before and after training).

DESCRIPTION (provided by applicant): Healthy older listeners show decline in cognitive and complex speech perception abilities. Complex speech perception in the real-world, including listening to highly variable speech sounds (phonemes) produced by multiple talkers and listening to speech in noise, has been shown to require cognitive resources. The overarching goal of the newly proposed research is to test the hypothesis that cognitive training preceding complex speech training will result in better real-world speech communication abilities in healthy older adults. This hypothesis is grounded in the decline-compensation model of the aging brain, which postulates that decline in sensory abilities (auditory cortex) can be compensated by increased engagement of general cognitive cortical regions such as the prefrontal cortex, which cognitive training is expected to provide. The PI's current R01 is examining speech learning in younger adults, with the hypothesis that efficacy of complex speech learning (multi-talker/high-variability sound-to-word learning) is mediated by cognitive brain regions (superior parietal lobule for auditory attention and prefrontal cortex for working memory). The purpose of this K02 award is to allow the PI to extend his current work in younger adults to the elderly population, including examinations of the neurophysiological underpinnings of the efficacy of prescribing cognitive training before multi-talker sound-to-word and speech in noise training. Per the decline-compensation model, we hypothesize that the engagement of cognitive brain regions post-training is critical to the success in complex speech learning. The two important issues concerning older adults addressed by this research is the trend for this population to seek cognitively stimulating post-retirement activities including effective second language learning programs and the need to overcome central auditory deficits (with speech perception in noise difficulty being the chief complaint) in order to participate fully in (noisy) everyday environments. This K02 award will also allow the PI to receive didactic and laboratory training in gerontology (including neuroimaging in older adults) and clinical research designs to prepare him for a life-long career as a clinician-translational researcher. PUBLIC HEALTH RELEVANCE: Many older adults experience difficulty understanding speech in real-world environments such as restaurants. Some elderly individuals reportedly avoid socializing (e.g., dining in restaurants) because it is difficult for them to communicate in such environments. While this difficulty can be related to their ears and to the fact that sounds are not loud enough for them to hear, reduced brain functions affecting memory and attention might also be playing a major role. Our research will seek to explore whether training focusing first on memory and attention prior to speech perception training of real-world environments could result in better overall spoken language communication in older adults;an additional goal is to examine the underlying brain responses to such possible improvements.

Perception of speech and music is known to rely to some extent on shared brain resources, but the extent to which those resources are shared, and how they are orchestrated is not known. With funding from the National Science Foundation, Dr. Patrick C. M. Wong and colleagues of Northwestern University, and Dr. Alice H. D. Chan of Nanyang Technological University of Singapore are investigating relationships between speech and music for perception and production. In the past, research in this area has focused on individuals with typical abilities and on individuals with extensive musical training. The current project examines the speech-music relationship from a different point of view. Namely, it considers what perceptual disorders in processing pitch reveal about speech and music. Pitch is ubiquitous in our environment. We rely on pitch to classify different types of environmental sounds, differentiate vocal sounds such as various patterns of crying, distinguish who is talking, identify the emotion of talkers, track the speech signal in adverse listening conditions, perceive musical melodies, and distinguish musical instruments. However, pitch perception can be difficult for an estimated 5% of the population in the Western world. This deficit, known as 'amusia' or 'musical tone deafness' (mTD), occurs in the absence of other known neurological or psychiatric disorders. Whether this deficit also affects other auditory domains is important to understand for its implications concerning the neural architecture of auditory perception. This project involves participants in the U.S. and in Singapore whose native language uses tone (pitch) contrasts to signal differences between words. If the brain resources required to process pitch are shared between speech and music, tone language speakers who suffer from mTD should show deficits in perceiving and producing linguistic pitch and musical pitch. The project is intended to expand our understanding about the organization of music and speech processing by our nervous system.

In addition to basic scientific information regarding speech and music, the research could lead to clinical applications. Tone deafness is not classified as a disorder by any medical or professional groups. The real-world impact of tone deafness has yet to be documented, and treatment research has not begun. This research could allow for a better understanding of the communicative consequences of tone deficits, which could ultimately lead to formal clinical recognition and treatment. Tone languages are estimated to be spoken by at least 1.66 billion people in the world, most of whom live in lower-middle income countries as classified by the World Bank. In the U.S., over 26% of non-native English or Spanish speakers (over 3.4 million total) speak a tone language, and this number is growing. Research into pitch perception and its communicative consequences has the potential to benefit large groups of individuals. The findings from this research are relevant to public and global health concerns and will be of interest to many individuals outside the English-speaking world, potentially increasing interest in international collaboration.

PROJECT SUMMARY (See instructions): The Human Subject Recruitment and Management Core (HSRM) will establish a Human Subjects Registry to support the collection and distribution of potential research participant information to investigators. The registry will include an extensive range of populations with speech, language, and/or hearing disorders studied by P30 investigators (Aim 1), with special emphasis on enrolling populations of high priority to NIDCD and performing more extensive initial assessment and screening of key patient populations: autism spectrum disorders, language based learning disorders, and older adults (Aim 2). Each of these patient populations is of high public health concern and a major focus of NIDCD priorities. They are also commonly seen in the clinics of the Roxelyn and Richard Pepper Department of Communication Sciences and Disorders (CSD). However, research with these populations involves labor and time intensive screening and diagnostic work, which can be prohibitive to laboratories without extensive and specialized resources in place for the assessment of each particular population. Core 1 will administer a common set of screening tools to these focused patient groups in order to reduce this burden, and facilitate research with these key populations. This screening will complement data contributed by individual laboratories in CSD and Linguistics, specializing with each population. Recruitment registry coordination staff will be hired to centralize the labor intensive recruitment and screening efforts currently performed separately by each Investigator, as well as to maintain these recruitment data in the registry for investigator access. Core 1 staff will liaise with the IRB to facilitate study enrollment of subjects obtained through the registry, and potential data exchange across laboratories that will facilitate cross-laboratory collaborations and new translational research endeavors. This core will interact closely with Core 2 to optimize software based tools to support the registry database. Together, these aims will provide a centralized, cost efficient resource for the labor intensive task of human subject recruitment, with an emphasis on speech, language, and/or hearing impaired populations studied across laboratories, and special populations of particular priority to NIDCD. The availability of a comprehensive registry of research participants will substantially increase the quantity of subjects available across laboratories, and increase opportunities for collaboration.