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Somali Community Services of Seattle

Somali Community Services of Seattle will organize a series of theater and acting trainings for youth during the summer of 2017. Participants will gain skills that will allow them to share their unique stories and experiences. They will be held twice per week beginning July 17 and concluding September 5, 2017. They will be held at the Rainier Arts Center located at 3515 S Alaska St. There will be a public talent show showcasing the youth performers on a date to be determined in the fall of 2017.

NIGMS - National Institute of General Medical Sciences

Project Summary Growing evidence suggests that stem cells are crucial to the success and transmission of many helminths. As helminths cause a wide variety of symptoms from intestinal distress and lethargy to organ failure, seizures and even death, discoveries in helminth biology have the potential to lessen human and animal suffering. Tapeworms have enormous capacity to grow, regenerate and reproduce in a stem cell-dependent manner, but pathologically significant tapeworm species are extremely difficult to study in the laboratory. We have performed foundational work on establishing Hymenolepis diminuta (rat tapeworm) into a tractable and modern model organism. Our long-term goal is to use H. diminuta to elucidate the molecular regulation of stem cells with potential application to helminths in general. Previous work shows that H. diminuta is a prolific regenerator, but the ability to regenerate is confined to the most anterior tissue of the neck/germinative region (GR). As tapeworms can regenerate fully reproductive structures from this tissue, fundamental somatic and germline fate transitions must occur here. Intriguingly, we find that a known reproductive regulator in flatworms: nonribosomal peptide synthetase (nrps) is strongly expressed in a spatially distinct region toward the anterior GR. Together, these observations suggest that there is a level of spatial regulation of stem cells that we can leverage. Our central hypothesis is that heterogeneous stem cell subpopulations and their niches are spatially restricted in the GR of H. diminuta. We propose to describe the distribution of stem cell subpopulations within the GR and perform functional studies to ascertain how these subpopulation states/types are determined. Our work is innovative because it exploits biological features of H. diminuta in combination with state-of-the-art methods in spatial transcriptomics and cell transplantations to functionally interrogate this parasite in ways that are near impossible in other tapeworms. We will test our hypothesis using three specific aims: Aim 1) Identify spatially distinct subpopulations of somatic and germline stem cells, Aim 2) Functionally determine stem cell hierarchies in the regeneration- competent GR and Aim 3) Explore nrps+ cells as a putative stem cell/germ cell niche. The expected outcome is that we will successfully determine somatic, germline and potentially pluripotent stem cell states that are spatially segregated within the GR. We will also determine if nrps serves as a bona fide stem cell or germ cell niche. Our proposal is significant because the gaps in our knowledge of how all important soma-germline stem cell transitions are regulated means that we are blind to potential vulnerabilities of these parasite or points of robustness for their success. Elucidating these mechanisms will strengthen our arsenal to target parasitic helminths.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Abstract The project aims to develop a platform that would enable whole-brain functional MRI (fMRI) during full night natural sleep in-sync to polysomnographic recordings (PSG), nearly as easily as in a PSG-only sleep lab. Sleep is vital for maintaining all aspects of human health. Extensive research has confirmed its role in homeostatic processes that are critical for brain health, especially in relation to aging and neurodegeneration. Yet, most of our knowledge of sleep neurophysiology in healthy individuals and patients has been limited by the capability of scalp EEG. EEG recordings, although extremely reliable, do not provide information with spatial specificity in the cortex nor do they provide information on the activity in subcortical areas, such as the medial temporal lobe and hippocampus, key brain areas involved in the study of cognitive decline due to dementia. fMRI provides superior spatial resolution of hemodynamics driven by neural activity, simultaneously in all brain areas, and provides a time resolution (seconds) relevant to sleep transitions (minutes) and their associated second scale events. However, attempts to obtain fMRI data during sleep have mostly been limited to light sleep in healthy young adults due to the difficulty of falling asleep and maintaining sleep in the MRI scanner environment where the acoustic noise is high, and participants are head-fixed in the coil. We will develop a novel platform to address these limitations and to enable simultaneous whole-night fMRI and polysomnographic recordings while the participants sleep naturally with minimal interruption. This platform will permit us to evaluate the coupling of fMRI brain activity and established polysomnographic recordings in a setup relevant for aged and clinical populations. Specifically, we will: (1) develop wearable high-density MRI head-cap arrays that are EEG compatible and allow the participants to adjust sleep posture while sleeping in the scanner environment; (2) adapt, and further develop silent fMRI using the looping-star sequence to eliminate acoustic noise while performing the scans; (3) develop an online real-time motion event classifier and scanner control for automatic sequence prescription for multiple head positions; (4) develop and integrate the analytical tools required to harmonize brain data recorded in multiple head positions; and (5) evaluate the platform in an aged population. Our proposed technology is highly innovative compared to the state of the art and addresses a significant need in the field of sleep studies. A success of the project will provide solution for simultaneous whole-night fMRI and polysomnographic recordings with quality comparable to that of clinical sleep labs outside MRI scanners. Our platform would open new diagnostic and research avenues, not possible today in patients and aged individuals.

NINDS - National Institute of Neurological Disorders and Stroke

ABSRACT: SourceSpikeNet – A biophysically grounded AI approach to spike detection in EEG Epilepsy affects approximately 3.4 million Americans, with 40% experiencing seizures despite medication and 50-60% continuing to have seizures after surgical intervention. Electroencephalogram (EEG) detection of interictal epileptiform discharges (IEDs) is crucial for diagnosis, medication selection, and surgical planning. However, current practice relies on subjective, qualitative identification of a small subset of IEDs, with significant inter-reviewer variability. State-of-the-art automated detectors suffer from high false alarm rates, creating an urgent unmet need for precise, objective IED identification. We propose SourceSpikeNet, a biophysically grounded artificial intelligence approach to IED detection that leverages known neurophysiology and electromagnetic physics to improve spatiotemporal accuracy. Our central hypothesis is that a biophysically informed AI can identify IEDs much more accurately than current methods. In Aim 1, we will characterize IED prototype timeseries patterns from 32,433 expert-annotated IEDs using inverse source modeling and self- supervised machine learning. In Aim 2, we will develop SourceSpikeNet by training a deep learning algorithm on an augmented dataset of 3,200,000 simulated spikes from 1,000 uniformly spaced cortical locations. In Aim 3, we will evaluate SourceSpikeNet's ability to detect all IEDs from 2,484 patients' continuous EEG recordings (3-7 days each) and compare comprehensive IED localization to traditional methodology. We expect that SourceSpikeNet will provide superior spatiotemporal localization of IEDs compared to current approaches, with lower false alarm rates and higher spatial resolution. The successful completion of this project will enhance the accuracy of IEDs as a biomarker for identifying seizure foci, potentially enabling higher surgical success rates and improved outcomes for epilepsy patients.

National Lottery Distribution Trust Fund

R2B+ ZAR annually for charities, arts, culture, sport, and the reconstruction and development fund.

South Carolina Arts Commission

South Carolina Arts Commission provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across SC.

South Carolina Arts Commission

The South Carolina Arts Commission provides annual operating and project grants to arts organizations statewide, supporting programming in visual arts, performing arts, literary arts, and arts education that enrich communities across the state.

South Carolina Arts Commission

Arts Education grants fund artist residencies, professional development for arts educators, and creative learning projects in South Carolina K-12 schools, expanding access to quality arts instruction for students across the state.

South Dakota Arts Council

The South Dakota Arts Council awards project grants to support arts programming, exhibitions, performances, and community arts activities that increase public access to the arts and strengthen cultural life across the state.

South Dakota Arts Council

Touring Arts grants help bring professional artists and performing arts groups to communities across South Dakota, particularly rural areas, ensuring all residents have access to quality arts experiences regardless of geography.

South Dakota Community Foundation

South Dakota Community Foundation ($400M in assets) supports nonprofits in SD through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

South Park Arts

South Park Arts located at 8201 10th Ave S, a volunteer-run community organization since 2005, would like to conduct a feasibility study engaging local businesses, to determine the organization's next steps. The feasibility study will be completed by early July 2019

Southwest Washington Community Foundation

Southwest Washington Community Foundation ($75M in assets) supports nonprofits in WA through grants focused on education, community development, health, arts. Awards range from $1,000 to $25,000.

Spartanburg County Foundation

Spartanburg County Foundation ($200M in assets) supports nonprofits in SC through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY / ABSTRACT Type 1 diabetes (T1D) is caused by T-cell mediated destruction of insulin-producing pancreatic beta cells. While notable progress has been made in predicting and delaying onset of T1D, our limited understanding of the factors that initiate and maintain this autoimmune attack continue to act as a major barrier to further progress. Increasing evidence points to the pancreas itself, including endocrine cells, exocrine cells, and the extracellular matrix, as possible contributors to the pathogenic immune activation. One factor that is known to contribute to immune cell activation, and that is altered in other pancreatic disease including cancer, is protein N-glycosylation, wherein complex carbohydrate chains called glycans are enzymatically attached to specific asparagine (called N-glycans) residues as proteins transit the endoplasmic reticulum and golgi complex. Glycosylation patterns influence protein stability, localization, and receptor binding, which can dramatically alter cell function and intercellular communication. Though the pancreatic glycome has been studied in pancreatic cancer, very little is known about how the glycome changes in diabetes pathogenesis, partially owing to the relative scarcity of appropriate human tissues to study and to the complexity of analysis methods required to measure protein glycosylation. While single cell transcriptomic data shows that expression of many of the enzymes involved in glycosylation are altered in T1D, it remains unknown how the pancreatic glycome changes during T1D pathogenesis, and whether altered glycosylation contributes to changes in pancreatic structure, cell composition, or immune cell infiltration. I hypothesize that N-glycosylation in the pancreas is altered as type 1 diabetes progresses, contributing to changes in immune cell localization and phenotype. I will employ two state-of-the-art imaging technologies to test this hypothesis in pancreas tissues from donors without diabetes, with positive auto-antibodies, or with recent-onset or long-standing T1D: 1) Imaging mass spectrometry will allow comprehensive quantitation of different N-glycans across entire tissue sections and at single-cell resolution, and 2) Multiplex immunofluorescence microscopy (CODEX) will be used to define pancreatic regions of interest and to quantify cell types and subtypes across the same tissue section. In Aim 1, I will test the hypothesis that the pancreatic N-glycome quantitatively changes throughout T1D progression. In Aim 2, I will test the hypothesis that regions of altered N-glycome signature are associated with changes in cellular composition and immune cell phenotypes. Completion of these aims will identify high level changes to post-translational protein processing signatures as T1D progresses. These results will lay the groundwork for future studies into mechanisms responsible for glycomic changes, identification of specific proteins that are affected, and definition of novel glycoprotein signatures that may be promising biomarkers or drug targets.

National Institutes of Health

Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) invites applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPORE). The program will fund P50 SPORE grants to support state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of an organ-specific cancer or a highly related group of cancers. For the purpose of this FOA, a group of highly related cancers are those that are derived from the same organ system, such as gastrointestinal, neuroendocrine, head and neck, and other cancers. Other programmatically appropriate groups of cancers may include those centered around a common biological mechanism critical for promoting tumorigenesis and/or cancer progression in organ sites that belong to different organ systems. For example, a SPORE may focus on cancers caused by the same infectious agent or cancers promoted and sustained by dysregulation of a common signaling pathway. In addition, a SPORE may focus on cross-cutting themes such as pediatric cancers or cancer health disparities. The research supported through this program must be translational and must stem from research on human biology using cellular, molecular, structural, biochemical, and/or genetic experimental approaches. SPORE projects must have the goal of reaching a translational human endpoint within the project period of the grant.

National Institutes of Health

Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) invites applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPORE). The program will fund P50 SPORE grants to support state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of an organ-specific cancer or a highly related group of cancers. For the purpose of this FOA, a group of highly related cancers are those that are derived from the same organ system, such as gastrointestinal, neuroendocrine, head and neck, and other cancers. Other programmatically appropriate groups of cancers may include those centered around a common biological mechanism critical for promoting tumorigenesis and/or cancer progression in organ sites that belong to different organ systems. For example, a SPORE may focus on cancers caused by the same infectious agent or cancers promoted and sustained by dysregulation of a common signaling pathway. In addition, a SPORE may focus on cross-cutting themes such as pediatric cancers or cancer health disparities. The research supported through this program must be translational and must stem from research on human biology using cellular, molecular, structural, biochemical, and/or genetic experimental approaches. SPORE projects must have the goal of reaching a translational human endpoint within the project period of the grant.

National Institutes of Health

<p>Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) invites applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPORE). This is a re-issuance of <a href="https://grants.nih.gov/grants/guide/pa-files/PAR-23-284.html">PAR-23-284</a>. The program will fund P50 SPORE grants to support state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of an organ-specific cancer or a highly related group of cancers. For the purpose of this NOFO, a group of highly related cancers are those that are derived from the same organ system, such as gastrointestinal, neuroendocrine, head and neck, and other cancers. Other programmatically appropriate groups of cancers may include those centered around a common biological mechanism critical for promoting tumorigenesis and/or cancer progression in organ sites that belong to different organ systems. For example, a SPORE may focus on cancers caused by the same infectious agent or cancers promoted and sustained by dysregulation of a common signaling pathway. In addition, a SPORE may focus on cross-cutting themes such as pediatric cancers or epigenetics. The research supported through this program must be translational and must stem from research on human biology using cellular, molecular, structural, biochemical, and/or genetic experimental approaches. SPORE projects must have the goal of reaching a translational human endpoint within the project period of the grant.</p>

National Institutes of Health

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) invites applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPORE). This is a re-issuance of PAR-23-284. The program will fund P50 SPORE grants to support state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of an organ-specific cancer or a highly related group of cancers. For the purpose of this NOFO, a group of highly related cancers are those that are derived from the same organ system, such as gastrointestinal, neuroendocrine, head and neck, and other cancers. Other programmatically appropriate groups of cancers may include those centered around a common biological mechanism critical for promoting tumorigenesis and/or cancer progression in organ sites that belong to different organ systems. For example, a SPORE may focus on cancers caused by the same infectious agent or cancers promoted and sustained by dysregulation of a common signaling pathway. In addition, a SPORE may focus on cross-cutting themes such as pediatric cancers or epigenetics. The research supported through this program must be translational and must stem from research on human biology using cellular, molecular, structural, biochemical, and/or genetic experimental approaches. SPORE projects must have the goal of reaching a translational human endpoint within the project period of the grant.

OD - NIH Office of the Director

PROJECT SUMMARY/ABSTRACT: This S10 Shared Instrumentation Grant application from Washington University (WashU) in St. Louis requests funds in partial support of the purchase of a Sybmia Pro.specta X3 scanner (Siemens Medical Solutions USA). This hybrid single photon emission computed tomography and x-ray computed tomography (SPECT/CT) system will be housed in a dedicated Nuclear Medicine research facility for the non-invasive assessment of therapeutic and diagnostic (theranostic) radiopharmaceuticals. This state-of-the-art instrument will be a critical, broadly used resource for the clinical and translational neuroscience, cardiovascular and oncology research programmes at WashU. The requested SPECT/CT will be the only research dedicated SPECT/CT system across the WashU clinical enterprise. At present, WashU through its affiliated Hospitals, has access to 7 SPECT/CT scanners across the medical campus. These are dedicated for standard of care and clinical trial workflows, 1 of them being at the Children’s hospital (out-of-reach for research), and 2 of the SPECT scanners are obsolete and only used for planar imaging. These systems are all >10 yr, and they are heavily utilized, at nearly 8 h of scan time per day average (utilization >85%), which does not include protocol development and maintenance. Access for research is highly restricted and there is no support for the special attention required for clinical research. Additionally, in the greater St. Louis region beyond WashU there is no research SPECT/CT hardware, and the nearest research SPECT/CT scanners are located at University of Missouri Veterinary Health Center (2.5 h drive), dedicated for non-human use. The Symbia Pro.specta incorporates advanced workflows including advanced iterative data driven motion correction features are critical for advanced quantitative imaging-; a redesigned quantitative framework for therapeutic absorbed dose assessment; and best-in-the-field collimators. The requested SPECT/CT scanner will anchor major new research efforts in theranostics for cancer, cardiovascular disease and neuroscience at WashU. Towards this end, Pamela Woodard, Radiology Chair and MIR Director, and Timothy Eberlein, Director, Alvin J. Siteman Cancer Center, have made substantial financial and administrative commitments to ensure the successful utilization of this instrument. These include funds for (1) installation and renovation costs, (2) adjacent radioactive handling and patient-administration space, (3) maintenance for the instrument, (4) pilot funds for protocol development and (5) personnel support. A new Section of Medical Physics is being established to harness the outstanding imaging science and translational radiopharmaceutical expertise at WashU that will be co-located with this centerpiece scanner. The combination of advanced instrumentation and robust support from our institution will enable groundbreaking discoveries and innovations that will benefit both our research community and patients, reflecting our dedication to excellence in scientific inquiry and healthcare.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT This S10 application requests a Cytek Aurora CS Spectral Cell Sorter for Sanford Burnham Prebys (SBP) to replace a 22-year-old FACSAriaIIu sorter that has experienced >45 days of downtime in the past 18 months and lacks service contract support, creating a critical bottleneck for time-sensitive experiments. Moreover, SBP's current cell sorting infrastructure cannot meet the growing demand for complex, high-parameter sorting required for cutting-edge immunological, cancer, aging, neuroscience, and skeletal muscle research by SBP's NIH-funded scientists. The Cytek Aurora CS offers revolutionary advantages including: (1) spectral technology with 64 fluorescence detectors across five lasers, enabling simultaneous analysis of 40+ parameters in a single experiment; (2) superior sensitivity for detecting low-abundance molecules; (3) advanced autofluorescence extraction capabilities to improve signal resolution in samples like brain tissue, primary tumor cells and liver samples. These features substantially improve the precision with which cell populations can be isolated. Further, the Aurora CS sorter offers seamless compatibility with our existing Aurora spectral analyzer for direct transfer of experimental protocols without panel redesign, accelerating research and reducing waste. The instrument will be housed in the SBP Flow Cytometry Shared Resource, which has demonstrated exceptional management of institutional flow cytometry equipment and provides expert technical support to ensure optimal utilization. The acquisition of this instrument is part of SBP's strategic plan to modernize the Flow Cytometry Shared Resource, in operation since 2002, and enhances the research environment by providing graduate students and postdoctoral fellows with access to state-of-the-art technology essential for developing advanced technical skills critical to the nation's future biomedical workforce. The instrument will serve fourteen NIH-funded investigators spanning multiple disciplines, with projects requiring isolation of rare cell populations for use in disease models and molecular studies including single-cell genomic and transcriptomic analyses. The acquisition of this instrument will significantly accelerate discoveries in cancer biology, immunology, neuroscience, aging and regenerative medicine at SBP, while establishing a technological foundation for future collaborative research initiatives.

ATSDR - Agency for Toxic Substances and Disease Registry

ABSTRACT Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with no cure, and although inflammation plays a significant role in the disease, gaps remain in leveraging this knowledge for personalized clinical outcome models and personalized therapeutics. Peripheral blood immune profiles—defined as the total numbers and activation states of specific peripheral immune cells—reflect overall inflammation, but methodologic gaps exist to characterize these immune profiles given limitations in conventional flow cytometry, hampering its widespread use for ALS. The long-term goal is to leverage immune profiles to identify dysregulated immune pathways that can be treated to slow or stop ALS progression. The overall objective in this proposal, being submitted in response to RFA-TS-25-036 Funding Option A, is to establish spectral flow cytometry as the state-of-the-art approach to characterize peripheral immune profiles in ALS. The central hypothesis is that spectral flow cytometry will yield rigor and reproducibility with fresh and frozen blood samples and will identify pro-inflammatory immune profiles for ALS clinical outcome prediction. The rationale is that establishing rigorous protocols for the widespread multicenter use of spectral flow cytometry in ALS will unlock the complex, but vast, potential of the immune system for improving diagnosis, prognosis, and drug development for all persons with ALS. The central hypothesis will be tested by pursuing two specific aims: 1) Utilize spectral flow cytometry to quantify inflammation in ALS peripheral blood biosamples and determine the consistency of immune markers between samples processed fresh versus frozen to inform multisite ALS studies; and 2) Determine the natural history, diagnostic, and prognostic significance of comprehensive longitudinal spectral flow cytometry immune profiles as an ALS inflammatory signature. Under the first Aim, spectral flow cytometry protocols will be optimized to characterize ALS inflammation in fresh and frozen samples, paving the way for its use in multisite ALS studies. Under the second Aim, immune profiles will be associated with important ALS clinical outcomes, such as case status and disease progression. The research proposed in this application is innovative, in the applicant’s opinion, because it moves the field in a new direction—bridging both mechanistic and knowledge gaps—by bringing the transformational potential of spectral flow cytometry to ALS, establishing the rigor needed to make the technology widely available to the ALS community, leveraging the resulting data to better understand the role of comprehensive immune profiles for ALS, and providing the foundation for future multisite studies. The proposed research is significant because peripheral blood immunophenotyping will enable improved ALS clinical outcome associations, and eventually therapeutic target identification, testing, and responder analysis.

OD - NIH Office of the Director

Project Summary The University of Nebraska Medical Center (UNMC) is requesting funds to purchase a BD FACSDiscover™ S8 Cell Sorter with Biosafety Cabinet with the overall goal of bringing state-of-the-art spectral imaging analysis and sorting to UNMC and nearby research institutions, and of enhancing cutting-edge biomedical research being conducted in the State of Nebraska. The FACSDiscover S8 Cell Sorter provides high-dimensional, spectral analysis and 6-way sorting using 5 lasers and 78 fluorescent detectors allowing for the use of expanded antibody panels compared to current instrumentation. The FACSDiscover S8 Cell Sorter also provides real-time computed images from up to 6 detectors on the blue laser, allowing analysis and sorting based on cell morphology, intracellular co-localization, internalization or phagocytosis of fluorescent particles, polarization, and cell cycle. The FACSDiscover S8 will replace two highly used cell sorters that have reached the end of their life cycle and will allow continued and enhanced support for a wide range of biomedical projects spanning a variety of disciplines including infectious disease, cancer, immunology, neurological and cognitive diseases, and drug development, including the 33 NIH-funded projects described in this application. In addition, as the only spectral imaging cell sorter within a 3-hour drive of Omaha, this instrument will provide additional capabilities to researchers at University of Nebraska- Lincoln, Creighton University, and Boys Town National Research Hospital. The FACSDiscover S8 will be housed in the UNMC Flow Cytometry Research Facility (FCRF). The director of the FCRF, Dr. Craig Semerad, PhD, and its two staff members, Ms. Victoria Smith and Holly Britton, who each have significant experience in flow cytometry analysis and sorting will provide expert technical support for the use of this instrument. Additional technical support from Dr. Ashok Mudgapalli, the Director of the UNMC Research Information Technology Office will ensure proper storage and archiving of user data. This proposal also enjoys strong institutional support from the Vice Chancellor of Research and the Director of the Buffett Cancer Center, who together will provide salary support and service agreement support for the FACSDiscover S8. The combination of strong user interest, diverse biomedical projects, technical expertise, administrative experience, and a solid long-term financial plan ensure the successful implementation, sustained support, and extensive use of the FACSDiscover S8 so that it will contribute to high-impact discoveries in biomedical research.

NIDCD - National Institute on Deafness and Other Communication Disorders

PROJECT SUMMARY Although hearing aids and cochlear implants (CIs) improve the ability of people with sensorineural hearing loss (SNHL) to communicate, performance remains stubbornly low, particularly in noisy backgrounds. This is a critical health issue, not least because of the strong association between hearing abilities and cognitive decline with age. Older adults, even those with typical hearing (TH), also experience deficits understanding speech in noise in ways that remain poorly understood. Our long-term goal is to uncover the mechanisms that limit auditory and speech perception under challenging acoustic conditions in adults with and without hearing loss across the lifespan. This goal is addressed under three specific aims that explore interlinked aspects of the spectro-temporal encoding of auditory and speech sounds. Under Aim 1, the fundamental mechanisms that allow us to detect and identify speech and non-speech sounds in noise are explored. A new hypothesis involving the processing of amplitude fluctuations across frequency is compared with the classic hypothesis involving the processing of energy changes across frequency. Empirical results in adults with SNHL, CIs, and TH across the lifespan will be compared with predictions from state-of-the-art computational models of the auditory periphery and midbrain. Under Aim 2, the relative contributions of peripheral and more central factors to deficits in speech perception in noise with hearing loss and age are studied using a novel intervention approach, rather than more traditional correlational methods. By manipulating the degree of peripheral spectral resolution and temporal fine structure cues available in the speech sounds themselves, the experiments test the hypothesis that the bulk of age effects for speech in noise can be accounted for by changes in peripheral representations. Under Aim 3, auditory and speech perception is studied with respect to the influence of spectral contrast and context effects. Perception is critically dependent on the surrounding context in which the sensory signals are received, but we know little about how these dependencies are altered by either age or hearing loss. The implication is that any changes in our ability to make use of sensory context may be impacted by sensory loss or age in ways that are not detected by standard clinical tests. Our experiments will provide both behavioral and neurophysiological measures of auditory and speech context effects in TH and SNHL across the adult lifespan to test the hypothesis that changes in peripheral processing with hearing loss and age can radically affect how our perception adjusts to the surrounding context, and therefore contributes to the unexplained difficulties in communication faced by older people with and without hearing loss in dynamic acoustic environments. Overall, the results of this project will shed new light on critical perceptual issues surrounding speech understanding in challenging acoustic environments and will contribute to developing new approaches to the diagnosis, treatment, and management of hearing loss.