NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS (NIDCD) Comprehensive Strategic Plan and Budget to Reduce and Ultimately Eliminate Health Disparities

It is estimated that one of every six Americans, people of both genders and of all ages and races, experiences some form of communication disorder (e.g., hearing impairment, dizziness, balance problems, smell and taste disorders, and voice, speech or language disturbances). Such disorders often compromise social, emotional, educational and vocational aspects of an individual's life. The cost of these disorders in terms of quality of life and unfulfilled potential is substantial

The relationship between frontotemporal effective connectivity during picture naming, behavior, and preserved cortical tissue in chronic aphasia

NIH National Institute on Deafness and Other Communication Disorders (NIDCD) grant 1P50DC01228

Na(V)1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons

Olfactory sensory neurons (OSNs) fire spontaneously as well as in response to odor; both forms of firing are physiologically important. We studied voltage-gated Na+ channels in OSNs to assess their role in spontaneous activity. Whole cell patch-clamp recordings from OSNs demonstrated both tetrodotoxin-sensitive and tetrodotoxin-resistant components of Na+ current. RT-PCR showed mRNAs for five of the nine different Na+ channel α-subunits in olfactory tissue; only one was tetrodotoxin resistant, the so-called cardiac subtype NaV1.5. Immunohistochemical analysis indicated that NaV1.5 is present in the apical knob of OSN dendrites but not in the axon. The NaV1.5 channels in OSNs exhibited two important features: 1) a half-inactivation potential near −100 mV, well below the resting potential, and 2) a window current centered near the resting potential. The negative half-inactivation potential renders most NaV1.5 channels in OSNs inactivated at the resting potential, while the window current indicates that the minor fraction of noninactivated NaV1.5 channels have a small probability of opening spontaneously at the resting potential. When the tetrodotoxin-sensitive Na+ channels were blocked by nanomolar tetrodotoxin at the resting potential, spontaneous firing was suppressed as expected. Furthermore, selectively blocking NaV1.5 channels with Zn2+ in the absence of tetrodotoxin also suppressed spontaneous firing, indicating that NaV1.5 channels are required for spontaneous activity despite resting inactivation. We propose that window currents produced by noninactivated NaV1.5 channels are one source of the generator potentials that trigger spontaneous firing, while the upstroke and propagation of action potentials in OSNs are borne by the tetrodotoxin-sensitive Na+ channel subtypes.This work was aided by support from Boston University, the Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD) P30 DC-04657; D. Restrepo, principal investigator], and NIDCD Grants DC-04863 to V. Dionne and DC-006070 to D. Restrepo and T. E. Finger. (Boston University; P30 DC-04657 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)]; DC-04863 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)]; DC-006070 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)])https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122723/Accepted manuscrip

Anomalous morphology in left hemisphere motor and premotor cortex of children who stutter

Stuttering is a neurodevelopmental disorder that affects the smooth flow of speech production. Stuttering onset occurs during a dynamic period of development when children first start learning to formulate sentences. Although most children grow out of stuttering naturally, ∼1% of all children develop persistent stuttering that can lead to significant psychosocial consequences throughout one’s life. To date, few studies have examined neural bases of stuttering in children who stutter, and even fewer have examined the basis for natural recovery versus persistence of stuttering. Here we report the first study to conduct surface-based analysis of the brain morphometric measures in children who stutter. We used FreeSurfer to extract cortical size and shape measures from structural MRI scans collected from the initial year of a longitudinal study involving 70 children (36 stuttering, 34 controls) in the 3–10-year range. The stuttering group was further divided into two groups: persistent and recovered, based on their later longitudinal visits that allowed determination of their eventual clinical outcome. A region of interest analysis that focused on the left hemisphere speech network and a whole-brain exploratory analysis were conducted to examine group differences and group × age interaction effects. We found that the persistent group could be differentiated from the control and recovered groups by reduced cortical thickness in left motor and lateral premotor cortical regions. The recovered group showed an age-related decrease in local gyrification in the left medial premotor cortex (supplementary motor area and and pre-supplementary motor area). These results provide strong evidence of a primary deficit in the left hemisphere speech network, specifically involving lateral premotor cortex and primary motor cortex, in persistent developmental stuttering. Results further point to a possible compensatory mechanism involving left medial premotor cortex in those who recover from childhood stuttering.This study was supported by Award Numbers R01DC011277 (SC) and R01DC007683 (FG) from the National Institute on Deafness and other Communication Disorders (NIDCD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDCD or the National Institutes of Health. (R01DC011277 - National Institute on Deafness and other Communication Disorders (NIDCD); R01DC007683 - National Institute on Deafness and other Communication Disorders (NIDCD))Accepted manuscrip

J Struct Biol

High-resolution imaging of hair-cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.R01 GM115972/NIGMS NIH HHS/National Institute of General Medical Sciences/United StatesP01 GM121203/NIGMS NIH HHS/National Institute of General Medical Sciences/United StatesP01 GM098412/NIGMS NIH HHS/National Institute of General Medical Sciences/United StatesP01 GM051487/NIGMS NIH HHS/National Institute of General Medical Sciences/United StatesP30 DC005983/NIDCD NIH HHS/National Institute on Deafness and Other Communication Disorders/United StatesR01 DC002368/NIDCD NIH HHS/National Institute on Deafness and Other Communication Disorders/United StatesR01 DC011034/NIDCD NIH HHS/National Institute on Deafness and Other Communication Disorders/United StatesS10 OD012372/ODCDC CDC HHS/Office of the Director/United States2020-05-01T00:00:00Z30822456PMC66843226542vault:3366

EEG complexity as a biomarker for autism spectrum disorder risk

BACKGROUND: Complex neurodevelopmental disorders may be characterized by subtle brain function signatures early in life before behavioral symptoms are apparent. Such endophenotypes may be measurable biomarkers for later cognitive impairments. The nonlinear complexity of electroencephalography (EEG) signals is believed to contain information about the architecture of the neural networks in the brain on many scales. Early detection of abnormalities in EEG signals may be an early biomarker for developmental cognitive disorders. The goal of this paper is to demonstrate that the modified multiscale entropy (mMSE) computed on the basis of resting state EEG data can be used as a biomarker of normal brain development and distinguish typically developing children from a group of infants at high risk for autism spectrum disorder (ASD), defined on the basis of an older sibling with ASD. METHODS: Using mMSE as a feature vector, a multiclass support vector machine algorithm was used to classify typically developing and high-risk groups. Classification was computed separately within each age group from 6 to 24 months. RESULTS: Multiscale entropy appears to go through a different developmental trajectory in infants at high risk for autism (HRA) than it does in typically developing controls. Differences appear to be greatest at ages 9 to 12 months. Using several machine learning algorithms with mMSE as a feature vector, infants were classified with over 80% accuracy into control and HRA groups at age 9 months. Classification accuracy for boys was close to 100% at age 9 months and remains high (70% to 90%) at ages 12 and 18 months. For girls, classification accuracy was highest at age 6 months, but declines thereafter. CONCLUSIONS: This proof-of-principle study suggests that mMSE computed from resting state EEG signals may be a useful biomarker for early detection of risk for ASD and abnormalities in cognitive development in infants. To our knowledge, this is the first demonstration of an information theoretic analysis of EEG data for biomarkers in infants at risk for a complex neurodevelopmental disorder.This research was supported by a grant from Autism Speaks (to HTF), National Institute on Deafness and Other Communication Disorders (NIDCD) grant R21 DC08647 (to HTF), NIDCD grant R01 DC 10290 (to HTF and CAN) and a grant from the Simons Foundation (to CAN and WJB). We thank the following people for their help in data collection: Tara Augenstein, Leah Casner, Laura Kasparian, Nina Leezenbaum, Vanessa Vogel-Farley and Annemarie Zuluaga. We are especially grateful to the families who participated in this study. (Autism Speaks; R21 DC08647 - National Institute on Deafness and Other Communication Disorders (NIDCD); R01 DC 10290 - National Institute on Deafness and Other Communication Disorders (NIDCD); Simons Foundation

EEG analytics for early detection of autism spectrum disorder: a data-driven approach

Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.This research was supported by National Institute of Mental Health (NIMH) grant R21 MH 093753 (to WJB), National Institute on Deafness and Other Communication Disorders (NIDCD) grant R21 DC08647 (to HTF), NIDCD grant R01 DC 10290 (to HTF and CAN) and a grant from the Simons Foundation (to CAN, HTF, and WJB). We are especially grateful to the staff and students who worked on the study and to the families who participated. (R21 MH 093753 - National Institute of Mental Health (NIMH); R21 DC08647 - National Institute on Deafness and Other Communication Disorders (NIDCD); R01 DC 10290 - NIDCD; Simons Foundation)Published versio

Sylvian fissure and parietal anatomy in children with autism spectrum disorder

Autism spectrum disorder (ASD) is characterized by deficits in social functioning and language and communication, with restricted interests or stereotyped behaviors. Anatomical differences have been found in the parietal cortex in children with ASD, but parietal subregions and associations between Sylvian fissure (SF) and parietal anatomy have not been explored. In this study, SF length and anterior and posterior parietal volumes were measured on MRI in 30 right-handed boys with ASD and 30 right-handed typically developing boys (7–14 years), matched on age and non-verbal IQ. There was leftward SF and anterior parietal asymmetry, and rightward posterior parietal asymmetry, across groups. There were associations between SF and parietal asymmetries, with slight group differences. Typical SF asymmetry was associated with typical anterior and posterior parietal asymmetry, in both groups. In the atypical SF asymmetry group, controls had atypical parietal asymmetry, whereas in ASD there were more equal numbers of individuals with typical as atypical anterior parietal asymmetry. We did not find significant anatomical-behavioral associations. Our findings of more individuals in the ASD group having a dissociation between cortical asymmetries warrants further investigation of these subgroups and emphasizes the importance of investigating anatomical relationships in addition to group differences in individual regions.This study was supported by a program project grant from the National Institute on Deafness and Other Communication Disorders (U19 DC 03610), which is part of the NICHD/NIDCD funded Collaborative Programs on Excellence in Autism, as well as funding for the GCRC at Boston University School of Medicine (M01-RR0533). We thank all of our research assistants for help in collecting the data and Andrew Silver, Melanee Schuring, Danielle Delosh, and Jeremy Siegal for completing the total hemisphere measurements. We also extend our sincere gratitude to the children and families who participated in this study. (U19 DC 03610 - National Institute on Deafness and Other Communication Disorders; NICHD/NIDCD; M01-RR0533 - Boston University School of Medicine)Published versio

"It Seems that Everyone in My Family Loses Their Hearing!" Results of a Study of Hereditary Factors in Adult-Onset Hearing Loss.

Gallaudet University, the University of Maryland School of Medicine, and SHHH are completing a study to determine the extent to which genetic factors are involved in hearing loss that occurs in adulthood. This study, the first of its kind, is funded by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health. The results of the first phase of this study are described in this article

What do foreign neighbors say about the mental lexicon?

A corpus analysis of phonological word-forms shows that English words have few phonological neighbors that are Spanish words. Concomitantly, Spanish words have few phonological neighbors that are English words. These observations appear to undermine certain accounts of bilingual language processing, and have significant implications for the processing and representation of word-forms in bilinguals.This research was supported in part by a grant from the National Institutes of Health to the University of Kansas through the Schiefelbusch Institute for Life Span Studies: National Institute on Deafness and Other Communication Disorders R01 DC 006472