Daniel A. Abrams - US grants

DESCRIPTION (provided by applicant): Temporal features in the speech signal are essential for normal speech perception in most languages. Nevertheless, the neuroanatomical basis for decoding temporal elements of speech in the human auditory system remains elusive. The primary goal of the proposed work is to test an influential hypothesis that describes how the central auditory system decodes two perceptually-relevant ranges of temporal modulations in speech: temporal modulations in the range of 150-300 msec and 20-50 msec. To this end, we will employ novel and powerful methods for probing central auditory function using functional magnetic resonance imaging (MRI). In one experiment, functional MRI will measure brain responses to speech stimuli that vary in these two temporal modulation ranges to identify neuroanatomical "fingerprints" associated with specific temporal features in speech. A second fMRI experiment will measure brain responses to speech sounds that vary according to rapidly changing spectral features to identify neuroanatomical structures underlying the discrimination of stop-consonant phonemes. Results will provide important knowledge regarding the structure and function of the human auditory system, and will further elucidate the biological bases of speech and language. These data will provide an essential foundation for studying populations who suffer from auditory temporal deficits associated with speech and language function, including reading-impaired and elderly individuals. PUBLIC HEALTH RELEVANCE: Properly hearing the "timing" of events in speech is critical for speech understanding, and here we seek to understand how the brain is able to efficiently sort-out timing information in speech. This is an important question since auditory timing deficits have been seen in clinical populations with hearing and language impairments, including elderly and reading-impaired individuals. Understanding how the healthy brain sorts-out auditory timing information will help us understand brain deficits in these clinical populations.

DESCRIPTION (provided by applicant): This is an application for an NIH K01 Mentored Research Scientist Development Award: Decoding neural systems underlying affective prosody in children with autism. The overall goal of the proposed work is to better understand the neural basis of auditory information processing deficits in children with autism. Children with autism often exhibit pragmatic language impairments, including impaired perception of emotional content in speech. My specific aim here is to better understand the neural basis of this phenomenon using multivariate pattern recognition techniques and network-based analyses applied to functional magnetic resonance imaging (MRI) data and state-of-the-art diffusion tensor imaging (DTI) data. To achieve this goal, I propose to conduct three experiments to investigate the functional and structural bases of affective prosody processing in children with ASD and TD children. In the first experiment, functional MRI and novel multivariate pattern recognition techniques will be used to examine discrimination of positively and negatively valenced speech stimuli in the brain of children with ASD and TD children. In the second experiment, I will assess the functional integrity of brain networks recruited during the perception of affective prosodic cues in children with ASD and TD children. In the third experiment, I will use DTI to investigate the structural integrity of white matter tracts that are critical for speech comprehension in children with ASD and TD children. Findings from these experiments will provide novel insights into the perceptual and brain bases of emotional processing of speech, and will enable a more thorough understanding of the cognitive and brain systems underlying pervasive social communication deficits in ASD. In addition to the proposed research, I will undergo a rigorous education and training plan to increase expertise in clinical aspects of autism research, the psychology and neuroscience of reward and emotion, and DTI. I will be mentored and trained by experts in the fields of clinical psychology, psychiatry, and affective and cognitive neuroscience. I will also gain a thorough understanding of the behavioral and diagnostic measures administered to children with ASD so I may use them in a highly informed manner in my current and future research. Formal coursework and attendance at seminars in the psychology of reward, emotion, neuroanatomy, structural neuroimaging, and clinical psychology will assist in achieving this goal. Completing the proposed research project will enable me to become a successful independent investigator in the field of auditory cognitive neuroscience.

Project Abstract Speech communication impairments, including persistent difficulties in understanding and interpreting verbal information during conversation, are a hallmark of childhood autism. Speech-based communication unfolds over time, and speech comprehension relies on: (1) anticipation of incoming speech as a means of predicting its content and (2) temporal integration of speech so a listener can accumulate information over time to decode meaning in an extended utterance. Prominent theories of autism spectrum disorder (ASD) posit deficits in contextual and global information processing, which are germane to the anticipation and integration of information during communication. Late childhood is a crucial period for increased and more complex social interactions, including extended discourse between communication partners. Little is known regarding anticipatory and integrative components of speech processing, and their contribution to social communication (SC) deficits, in children with ASD. Advances in experimental design and computational analysis of human brain imaging data provide a unique opportunity to probe dynamic components of speech comprehension during naturalistic social interactions in children with ASD, which are difficult to ascertain using behavioral methods alone. Leveraging innovative fMRI experimental designs, we will for the first time investigate anticipatory and integrative aspects of naturalistic communication in children with ASD. Our overarching goal is to identify the neurocognitive mechanisms underlying speech comprehension deficits during naturalistic communication in children with ASD. The proposed studies include both speaker-listener brain coupling and temporal integration paradigms and build on our high-impact line of voice perception research in children with ASD. We hypothesize that children with ASD will show deficits in dynamic mechanisms of speech comprehension including anticipatory, reactive, and integrative processing with dissociable patterns of dysfunction in the default mode network (DMN), anchored in medial prefrontal cortex (mPFC) and posterior medial cortex (PMC), and lateral frontoparietal network (LFPN). While the DMN is often considered a ?task- negative? network, evidence shows that the DMN is crucial for processing social information, including narrative processing, and is closely linked to SC deficits in ASD. We hypothesize a link between these dynamic mechanisms and comprehension of global, but not local, narrative information, supporting the Weak Central Coherence model of ASD. Findings will provide new insights into speech comprehension impairments and advance our understanding of the role of the DMN in SC and ASD. Our studies will provide critical information regarding the neurobiological origins of communication impairments in ASD and will inform the development of age-appropriate treatment for older children with ASD. Our aims are in line with the NIH directive on Autism Research (PA-18-400), emphasizing brain mechanisms and sophisticated measures of social communication.

Project Abstract Alzheimer?s disease (AD) is a progressive and severely debilitating disease that negatively affects cognitive and memory function and is linked to increased disability in everyday functioning and risk of mortality. Language function is a crucial area of impairment for AD. Individuals with AD show a wide range of language difficulties which are thought to lead to social isolation in affected individuals, negatively affecting quality of life and well-being for patients, caregivers, and family members. The major goal of our Administrative Supplement is to advance our understanding of the brain mechanisms underlying speech comprehension deficits in patients with AD. To accomplish this goal, we will leverage fMRI task paradigms and neurocognitive models we have recently developed as part of the parent project and ongoing work in collaboration with the Stanford Alzheimer?s Disease Research Center (ADRC). We now propose to extend our original aims with two new Aims designed to build on these findings by examining anticipatory and integrative components of speech processing, with a focus on aberrant organization of the default mode network, in patients with early AD. Critically, to achieve this goal, we will apply the novel experimental and analytic approaches developed by the parent project at Stanford to AD data collected as part of the proposed supplement and resources provided by the Stanford ADRC (P30AG066515) Clinical Core and Imaging Core. Specifically, we will investigate (1) speaker-listener brain coupling during natural speech communication and its relation to narrative comprehension and functional communication abilities in AD and age-matched healthy controls; and (2) the integrity of temporal integration windows underlying naturalistic verbal communication and its relation to narrative comprehension and functional communication abilities in AD and age-matched healthy controls. Our studies will provide critical information regarding the neurobiological origins of communication impairments in AD and will inform therapies and strategies aimed at improving language and social function in dementia.