Tyler K. Perrachione, Ph.D. - US grants

? DESCRIPTION (provided by applicant): Phonological working memory is the mechanism by which language-relevant sounds are maintained in short- term memory. Phonological working memory is a core construct in cognitive, developmental, and clinical neuropsychology, as well as speech-language pathology, and plays an important role in language acquisition, vocabulary development, learning to read, and language comprehension. Phonological working memory deficits are characteristic of numerous developmental disorders of communication, including developmental language disorder (specific language impairment), developmental reading disorder (dyslexia), autism, and Down syndrome. Even in adulthood, phonological working memory deficits remain deleterious to the language abilities and psychosocial functioning of individuals with developmental language disorders. However, there has been no prior attempt to investigate the brain bases of phonological working memory using tasks analogous to clinically sensitive measures such as nonword repetition. Moreover, virtually nothing is known about how phonological working memory impairments in individuals with developmental language disorders arise from differences in neurophysiology or neuroanatomy. Correspondingly, the first goal of this project is to deter- mine the normative neural systems recruited by clinical phonological working memory assessments in the brains of adults with typical language abilities (Aim 1). Critically, we will ascertain whether the brain bases of phonological working memory are related to neural systems underlying domain-specific linguistic processing or domain-general cognitive abilities. This will help reconcile two competing theories about how phonological working memory works in the brain, as well as inform the clinical interpretation of nonword repetition tests. The second goal of this project is to examine phonological working memory in the brains of adults with persistent developmental language disorder, including how they differ from controls and how individual variability in neural responses is related to behavioral differences in language ability (Aim 2). Finally, we will collect pilot data from a smaller sample of children with developmental language disorder in support of future research aimed at understanding brain differences in children with developmental language disorders.

PROJECT SUMMARY / ABSTRACT The long-term objectives of this project are to identify whether there are any structural differences that distinguish the brains of children or adults with developmental reading disorders (dyslexia) and how these differences correspond to behavioral heterogeneity in reading impairment across development. Dyslexia is a neurodevelopmental disorder that specifically and often profoundly impairs the ability to acquire accurate and fluent reading skills. However, decades of research have failed to converge on one or more signature differences in the brains of children or adults with dyslexia that reliably, sensitively, or specifically distinguish impaired versus typical reading development. Drawing from numerous independent datasets collected by the investigators' labs over the past decade, this project will assemble and analyze the largest sample of structural brain scans ever studied from children, adolescents, and adults with developmental dyslexia and typical reading development. This combined dataset includes over 1200 structural brain scans obtained from individuals between the ages of 4 and 40 years old, for whom extensive reading and cognitive assessments were performed, and approximately 50% of whom have dyslexia. This dataset will be used to address two aims: In Aim 1, this study will explore whether structural brain features differ between individuals with and without dyslexia. Features to be studied include (1) macroanatomical morphology of the temporal lobe, such as patterns of Heschl's gyrus reduplication or planum temporale lateralization; (2) regional morphometric differences in gray or white matter volumes or their lateralization; and (3) geometric differences in cortical thickness, curvature, and surface area. Variation in these features will also be analyzed in the context of component reading skills, such as phonological awareness and rapid naming. In Aim 2, this study will use the processed dataset to build a model of the developmental trajectory of brain maturation in dyslexia compared to typical reading. This model will be used to evaluate current theories about developmental versus endogenous factors affecting reading impairment. Identifying the neuroanatomical substrate or substrates that are related to reading impairment, and how these change across development, is a key step in understanding the biological basis of dyslexia. A stronger scientific understanding of the causes and prognosis of developmental reading impairments will build a foundation upon which diagnoses can be obtained both earlier and with greater specificity, and upon which behavioral interventions can be deployed more efficaciously, ultimately to ensure that all children have the chance to achieve their full potential for healthy and productive lives.

This project will determine whether formal musical training is associated with enhanced neural processing and perception of sounds, including speech in noisy backgrounds. Music forms an important part of the lives of millions of people around the world, and it is one of the few universals shared by all known human cultures. Yet its utility and potential evolutionary advantages remain a mystery. This project will test the hypothesis that early musical exposure has benefits that extend beyond music to critical aspects of human communication, such as speech perception in noise. In addition, the investigators will test whether early musical training is associated with less severe effects of aging on the ability to understand speech in noisy backgrounds. Degraded ability to understand speech in noise is a common complaint among older listeners and hearing loss has been shown to be associated with social isolation and more rapid cognitive and health declines. If formal musical training is shown to affect improved perception and speech communication in later life, the outcomes could have a potentially major impact on quality of life,

Earlier studies have suggested relationships between early musical training and improved auditory neural processing and perception, but the studies' impact has been limited by small sample numbers and inconsistent methods between different studies. This project will test a large number of participants (N=360) with uniform recruitment criteria and testing protocols across six different sites. Measures will include the neural frequency following response (FFR) to speech sounds, behavioral frequency selectivity, speech perception in noise, speech perception against a background of competing talkers, pitch discrimination, and auditory masking. The participants will also complete other assessments, including a personality inventory questionnaire, a profile of musical perception skills, a spatial reasoning test to assess general cognitive ability, as well as a background questionnaire to determine socio-economic status, education, and musical background. Participants will be selected to span a wide range of ages and musical experience. The neural data and the speech perception measures will be related to factors of musical training, such as the number of years of musical training and the age at which musical training began. Scientific rigor will be assured by preregistering the study and the analyses and by making the data and analysis code publicly available via a dedicated website.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.