Gregory S Hickok - US grants

The long range goal of this project is to map the neurobiology of auditory language perception, both in terms of its linguistic sub-components and in terms of its domain specificity. The advent of functional magnetic resonance imaging (fMRI)--a non- invasive, high resolution functional brain imaging technique--has made the realization of this goal a real possibility in the near future. Because optimal methodological procedures for fMR imaging have yet to be worked out satisfactorily we propose a relatively small set of theoretically motivated experiments that we will carry out using protocols that can inform methodological as well as theoretical questions. Aim Concerning the Neural Organization of Language. 1. To map the extent of neural tissue involved in processing auditory language at the sentence level--a level of linguistic analysis which has been prominent in cognitive and linguistic theories but has yet to be investigated thoroughly using functional imaging techniques. 2. To determine the specificity of neural systems involved in linguistic vs. non- linguistic auditory perception. We contrast perception of sentences with perception of a range of non-linguistic auditory stimuli each of which controls for specific aspects of sentence processing such as temporal acoustic processing (backwards sentences), hierarchical structure processing (music), processing meaningful strings of sounds (environmental sound "events"). We also investigate the role of expertise in auditory processing and the neural correlates of hearing a single stimulus as linguistic versus non-linguistic signal. 3. To investigate the extent to which different aspects of the linguistic signal (prosody, lexical-semantic content, syntax) are processed in distinct neural systems. Aims Concerning Methodology. 1. To investigate reliability issues: test-retest reliability, reliability of localization, and reliability as seen in terms of repetition effects. 2. To examine empirically the cognitive basis of task effects in neuroimaging, namely, to answer the question, can task manipulations provide a window on the neural basis of linguistic perception or are we simply measuring task-specific effects. We propose a set of selective attention experiments (a widely used task manipulation) to investigate the issue. 3. Our third goal is to explore the utility of the single trial presentation format. Our prior work has demonstrated that one can present stimuli in single trials (rather than blocks of such stimuli) and obtain reliable activations, perhaps with increased sensitivity. This radically increases the flexibility of experimental design in fMRI. We assess the validity of the technique in several experiments.

Natural sounds are complex high-dimensional signals. The "cocktail-party phenomenon" in the hearing sciences is a classic example of the brain's ability to parse out and attend to a particular dynamic signal (speech) in the presence of multiple extraneous (non-signal) sounds, all of which reach the ears concurrently and continuously vary in pitch and location as a function of time. The ability to identify a relevant signal out of this "acoustic mixture" far outdistances that of the most sophisticated current automated speech-recognition systems. To understand how people process complex sounds that dynamically vary in time, space, and frequency, scientists must determine how the brain organizes these auditory dimensions. With support from the National Science Foundation, Dr. Saberi and his colleagues will use neuroimaging techniques to systematically map the neural landscape that underlies the functional organization of brain regions responsive to temporal, spatial, and spectral aspects of complex sounds.

The broader impacts of this project include applications to automated speech-recognition systems, development of auditory navigation systems for the blind, improved signal-processing by auditory prostheses for the hard-of-hearing and cochlear-implant users, and a deeper understanding of cortically-based auditory deficits in humans. The project integrates research and education by providing opportunities for graduate and undergraduate students to engage in research, and by complementing the planned development of an undergraduate and Ph.D. program in cognitive neuroscience at UCI and an interdisciplinary Center for Cognitive Neuroscience.

DESCRIPTION (provided by applicant): Auditory comprehension of language is fundamental to human communication and is often disrupted in neurological disorders for reasons that are incompletely understood. The overarching goal of the proposal is to understand the neural basis of auditory language comprehension and therefore open the door to effective interventions. We use complementary lesion/stroke-based and functional MRI methods to address three specific aims. Aim 1: Understand the neural basis of speech perception. The idea that the motor system may play a prominent role in speech perception has gained much popularity. We have argued instead that speech perception is bilaterally organized in the superior temporal lobes with minimal frontal/motor modulation. Experiments proposed under this aim test these competing ideas using both comprehension and syllable discrimination tasks and signal detection methods. Aim 2: Understand the role of extra-auditory influences on speech perception/comprehension. Speech perception is influenced by contextual information. Here we examine the influence of two cues, visual speech and word-level information. We hypothesize that temporal lobe circuits are primarily responsible for both of these sources of influence on speech perception. Our proposed studies will test this hypothesis. Aim 3: Understand the neural basis of sentence-level processing. Speech perception and word comprehension are critical for comprehension, but effective communication relies additionally on higher-order processes such as those involved in sentence comprehension. We propose studies aimed at testing our hypothesis that anterior temporal regions are particularly important for integrating lexical and syntactic information to derive sentence meaning. Methodologically, this program is driven by a commitment to the view that multiple methods are required for deriving a complete picture of a neural process. To speed the pace of lesion work, which can be laboriously slow, we have developed a Multisite Aphasia Research Consortium (MARC) that will enable us to collect data at an unprecedented pace. This will remove a critical barrier to rapid progress by quickly accruing the large samples needed for quantitative lesion-behavior correlation analyses.

DESCRIPTION (provided by applicant): The functional anatomy of the planum temporale (PT) has been of great theoretical interest for decades, and a focus of recent clinical studies of a number of disorders ranging from autism to schizophrenia. Although the (left) PT was initially thought to subserve language functions, recent basic research has shown that it is multifunctional, being implicated in such diverse processing domains as speech perception and production, tonal processing, auditory-motor integration, spatial hearing, and multi-sensory integration. Given the potential importance of the PT in both theoretical models of cortical function for a range of abilities as well as its widespread clinical implications, a more thorough understanding of the functional organization of the PT is sorely needed. The present proposal seeks to fill this gap through a series of fMRI studies using within subject designs, and organized around four specific aims. Aim 1 is to assess activation patterns for several functions known to activate the PT, including speech perception/production, tonal/melodic perception, sensory-motor integration, visual speech perception, and spatial hearing. Aim 2 seeks to understand the functional basis for sensory-motor activations in the PT. Sensory-motor behaviors have been strongly associated with the PT (particular on the left) both clinically and functionally. This aim examines whether PT sensory-motor activations are more strongly aligned with the auditory system (as is typically thought) or to the vocal tract articulator system (as we have recently hypothesized). In addition, we examine this system's role in temporal sequence processing, which we believe is connected to sensory-motor function. Aim 3 is to identify neural networks supporting the interaction of spatial hearing and speech processing. Both speech-related and spatial hearing- related functions have been associated with PT function. We examine a possible interaction of these two functions in connection with auditory stream segmentation, in particular whether activation in the PT reflects the use of spatial cues to segment auditory information into distinct objects. Finally, Aim 4 is to map the relation between spatial-speech integration and visual-speech integration. It is well known that auditory stream segregation processes can make use not only of spatial cues, but also of visual speech cues. Interestingly, processing both of these cues involves the PT suggesting a possible connection. PUBLIC HEALTH RELEVANCE The proposed research is of importance from a public-health standpoint because in recent clinical studies the planum temporale has been implicated in a number of disorders ranging from autism to schizophrenia. This brain region appears to be involved in several critical functions from language processing to integration of auditory, visual, and motor functions. In spite of its central role in sensory/cognitive functions, very little is known about how this brain area is organized, and given its widespread clinical importance, a more thorough understanding of the functional organization of this region may lead to more effective treatment strategies for cognitive dysfunctions.

DESCRIPTION (provided by applicant): The primary goal of this application is to promote research and training in the neurobiology of speech and language via support for an annual scientific conference, the Neurobiology of Language Conference (NLC). The NLC fills a much-needed gap in scientific meetings on the neural basis of language by emphasizing the strongest work on the integration of neuroscience research and communication disorders with cognitive, linguistic, psycholinguistic, perceptual, and motor control models of speech and language. We have the following five specific aims. (1) To support an annual meeting on the Neurobiology of Language with the aim of providing a forum for the interaction of researchers in the full range of allied areas including neuroscience, genetics, communications disorders, cognitive psychology, linguistics, psycholinguistics, neurolinguistics, perception, motor control, computational modeling, and neural and psychophysical methods. (2) To expand the breadth of knowledge of researchers in the field by bringing in distinguished keynote speakers in neuroscience and biology. (3) To advance the training and education in the neurobiology of language by providing student scholarships for conference attendance. (4) To promote diversity in the field by providing scholarships for conference attendance to under-represented groups. Because the NLC meeting brings together a broad range of language scientists who don't normally interact regularly, we believe the meeting will lead to valuable new interactions, collaborations, and novel ideas in the Neurobiology of Language, including both basic scientific findings and applied findings in physiologically-based therapies for neurogenic language disorders. PUBLIC HEALTH RELEVANCE: Language disorders affect millions of people in the United States. There is an extensive research community, with much of this research funded by NIDCD, which targets both basic and clinically-oriented research on the neural basis of language and language disorders. By providing a forum for the communication of new research findings and emerging trends, the Neurobiology of Language Conference will play a pivotal role in scientific progress aimed at understanding, diagnosing, and treating language disorders.

Our brains have evolved a highly-sophisticated auditory system for the analysis of sounds, which underlies more complicated abilities such as speech perception. We currently know very little about the organization of human auditory cortex at the interface between the auditory inputs from the peripheral sensory receptors in the ear and the higher-level language systems of the brain. Understanding the nature of the inputs to higher-level speech perception systems is critical to understanding what kind of information is ultimately used in speech perception and how this information is extracted computationally. With support from the National Science Foundation, Dr. Alyssa Brewer and colleagues Dr. Gregory Hickok and Dr. Kourosh Saberi will use functional magnetic resonance imaging (fMRI) to measure the functional organization of the human auditory cortex with a level of detail that has not previously been achieved. They will then use these measurements to examine how cortical responses to particular types of speech and speech-related stimuli relate to these lower-level cortical regions. This study will thus provide the first systematic measurements of the human speech perception system from the fundamental organization of auditory cortex to cortical speech representations.

Acquired and developmental disorders of hearing, speech and language affect millions of individuals. The knowledge gained from this study will give us a better understanding of the organization and function of these systems, which will have clinical benefits for the treatment of both peripheral auditory diseases and central language disorders. The research team will continue to share the results through "Brain Day" programs in the local K-8 elementary schools to bring the excitement of neuroscience research to the local communities. Furthermore, PI Brewer has developed ongoing "Brilliant Brain" workshops with Girls Inc., which include special presentations and summer workshops on the organization, function, and diseases of the brain. Girls Inc. is a non-profit organization that provides research and STEM-based experiences to girls ages 6-18 across the U.S. and Canada designed to help them navigate gender, economic, and social barriers. Finally, this study incorporates training of new neuroscientists at the undergraduate, graduate, and postdoctoral levels for whom these studies will serve as a foundation of neuroscience research.

Project Summary: Project 4 Model-driven therapies are only as effective as the models that drive them. The goal of Project 4 is to establish a synergistic interaction between clinical and theoretical progress in language science. Data collected as part of Projects 1 and 2 will serve as input to basic science research that will lead to new knowledge regarding the computational and neural foundation of speech production. And feeding back in the other direction, basic science models of speech production will be explored as possible diagnostic and treatment outcome measure tools, opening the door to a new era in model-driven aphasia treatment. Aim 1: Map the neural organization of computational subcomponents of naming. Naming is a multistep process. A complete understanding of its neural basis, and how it can breakdown in aphasia, depends on our ability to map the computational subcomponents of the process. Using both VLSM (error type maps) and VLPM (parameter maps), in this aim we investigate the neural organization of the subcomponents of naming in chronic and acute stroke. Aim 2: Improve and extend the model and the neurobiological mappings. While existing computational models are successful in accounting for the range of naming response types that have been fed into the models, aphasic production deficits are rather more complex than standard operational definitions admit. For this reason, and in keeping with the overall goal of the P50 to bring together theory and practice, Aim 2 seeks to push the computational models more toward clinical reality. We will use our recently-developed SLAM model to simulate and map speech repetition behavior and we will map the neural basis of a common behavior in both naming and connected speech context, self-correction. Aim 3: Assess the utility of model-driven diagnostics. The premise of Project 1 is that identifying functional deficits to the dorsal or ventral streams? i.e., dorsal stream aphasia (DSA) vs. ventral stream aphasia (VSA) vs. dual stream aphasia (DuSA)?provides useful information for aphasia treatment. In Project 1, DSA, VSA, and DuSA are classified on the basis of lesion location, which is a good (arguably the best available) proxy for the functional deficit that is targeted by the subsequent treatment. The possibility we will assess in this aim is whether we can do better at classifying patients pretreatment by measuring their functional deficit ?directly? using functional/computational models rather than relying on a lesion-based proxy. This investigation could result in the development of new, clinically available assessment tools for aphasia.