Mr. Chairman and Members of the Committee, the President in his 2000 budget has proposed that the National Institute on Deafness and Other Communication Disorders receive $235,297,000, an increase of $5,619,000 over the non-AIDS portion of the comparable FY 1999 appropriation. Including the estimated allocation for AIDS in both years, total support proposed for NIDCD is $237,171,000, an increase of $5,551,000 over the FY 1999 appropriation. Funds for NIDCD efforts in AIDS research are included within the Office of AIDS Research budget request. I am honored to appear before you as the Director of the National Institute on Deafness and Other Communication Disorders (NIDCD).

NIDCD conducts and supports research and research training on normal processes and disorders of hearing, balance, smell, taste, voice, speech, and language. These processes are fundamental both to the way people perceive the surrounding world and to their ability to communicate effectively with other individuals. As we approach the end of the century, effective human communication is an increasingly important requirement for a wide range of employment opportunities. Within the last year, we have witnessed outstanding research progress by NIDCD-supported scientists and clinicians, progress further accelerated by the efforts of other institutes at the NIH. This progress is lighting the path for ongoing and future research studies to achieve a pressing goal: to help individuals with communication and sensory systems disorders.

Early Identification of Hearing Impairment: Early Intervention Results in Better Language Skills
Since about 33 children are born each day in the United States with a significant hearing impairment, early identification of these affected children has become an important public health objective. Recent results from NIDCD-supported research show that children whose hearing impairments are identified by six months of age, and who consequently receive appropriate intervention, demonstrate significantly better language scores than children whose impairment was initially identified after six months of age. For children with normal cognitive abilities, this language advantage was found across all tested ages, communication modes, degrees of hearing loss, and socioeconomic strata.

In 1993, an NIH Consensus Development Conference on the Early Identification of Hearing Impairment in Infants and Young Children recommended universal screening of all infants for hearing impairment. In the near future approximately 19 states will implement programs to screen all neonates for hearing impairment before discharge from the hospital. [Exhibit 1] This number is expected to increase rapidly in the next decade. Implementation of intervention strategies that optimize language skills is a necessary sequel to early identification.

The need to define and validate optimal intervention strategies for infants with all degrees of hearing impairment is clear. In March 1998, the NIDCD convened a Working Group on the Early Identification of Hearing Impairment to provide advice on the most pressing research questions regarding diagnostic and intervention strategies that follow neonatal hearing screening. The workshop focused on strategies that are appropriate immediately after an infant is referred from the screening program, depending on the degree of hearing impairment identified. Current studies indicate that approximately ten to twenty percent of the infants identified through neonatal hearing screening have profound hearing impairment. The other eighty to ninety percent have lesser, but varied, degrees of hearing impairment, defining additional populations of infants for whom optimal intervention strategies remain to be developed and validated through research. In October 1998, NIDCD solicited grant applications to develop and validate these needed intervention strategies. We anticipate the results of a recently concluded, multi-center collaborative project which will provide critical information regarding efficacy and cost of different screening protocols.

Discovering the Genes Underlying Hereditary Hearing Impairment
Roughly one child in two thousand born in the United States has hereditary hearing impairment of sufficient severity to compromise the development of normal language skills. Some of these children have hearing impairment together with other problems, a condition known as syndromic hearing impairment. Many of the genes where mutations cause syndromic hearing impairment have been identified. [Exhibit 2] However, about seventy percent of children with hereditary hearing impairment have no obvious associated clinical abnormality, and their hearing impairment is referred to as nonsyndromic hereditary hearing impairment. Beginning in 1992, the location in the human genome of over forty different genes related to nonsyndromic hearing impairment has been reported. Many of these advances resulted from extramural NIDCD support coupled with research efforts in NIDCD Intramural laboratories.

Within the last two years, great progress has been made in bridging the gap between determining the location of a gene involved in nonsyndromic hereditary hearing impairment and using this knowledge to clone the gene. As of January 1999, eight genes have been cloned, six within the last year. The identity of genes where mutations cause hearing impairment has taught us much about the molecular processes that are essential for normal hearing. These genes encode proteins that serve many different functions, including the transport of molecules between cells, forming channels that transport molecules into and out of cells, gene regulation, and moving molecular "cargo" within cells. Mutations in one of these genes, connexin 26, appears to be responsible for as much as forty percent of hereditary hearing impairment in the United States, and an even greater percentage in certain population subgroups.

With some of the genes in hand and more on the way, scientists and clinicians are turning their attention to unraveling the genetic epidemiology of hereditary hearing impairment. A number of important questions are being addressed using these new research tools, including: what fraction of the cases of hereditary hearing impairment result from mutations in each of the eight genes? In different families transmitting the same hereditary hearing impairment gene, is the same mutation in the gene found, or are there different mutations in different families? Does the type of mutation inform us about the onset or severity of hearing impairment? What are the differences in the genetic epidemiology of hereditary hearing impairment in different population groups, or in different parts of the world? Answers to these questions will play an important role in guiding clinicians and scientists in their efforts to translate these scientific advances into genetic diagnostic tests to provide a precise genetic diagnosis soon after birth, leading to early and appropriate intervention strategies to optimize language skills.

Neuroimaging Reveals Brain Activity Associated With Language
The development of sophisticated neuroimaging techniques has allowed researchers to monitor brain activity patterns associated with perception and production of language, both spoken and signed. For example, functional magnetic resonance imaging (fMRI) findings suggest that delayed acquisition of language leads to anomalous patterns of brain activity when language is ultimately acquired. Using fMRI, NIDCD-supported investigators have documented reorganization of brain activity following treatment for acquired reading disorders following stroke. fMRI performed during a reading task before and after treatment indicated a shift in brain activation from the left angular gyrus to the left lingual gyrus, showing that it is possible to alter brain activity patterns with therapy for acquired language disorders. Continued investigations of normal and disordered language processes using neuroimaging tools will refine our understanding of brain function, improve our ability to identify the underlying causes of language impairment, and to document and refine the efficacy of interventions. Neuroimaging studies have had, and most certainly will continue to have, a profound impact on the study of language and language impairments.

Persistent Stuttering Has a Genetic Etiology
Stuttering is a speech disorder that typically begins in early childhood. Although it is estimated that more than two million Americans stutter, little is known about the cause of stuttering. At least five percent of children ages two to five are affected by stuttering. About twenty percent of these children develop chronic stuttering persisting into adult life, while the remaining eighty percent recover spontaneously. When stuttering persists, the disorder impairs verbal communication often resulting in difficulties with emotional and social adjustment. NIDCD supports research to develop methods to identify which young children are at high risk for persistent stuttering. This research has confirmed earlier research indicating that the tendency to stutter runs in families. Moreover, if persistent stuttering is observed in a child's family, the child is at increased risk for developing persistent stuttering. These findings help to inform clinicians about which children are more likely to have stuttering that persists into adult life, the group in greatest need of intense intervention.

Sensorineural Regeneration
Our sensory systems possess exquisite sensitivity, connecting us to our physical world and providing indispensable aids for daily life. Some of our sensory systems, such as the senses of smell and taste, have the capacity to continuously replace sensory cells throughout adult life. The regenerative abilities of these sensory systems stand in sharp contrast to the limited potential for regeneration seen elsewhere in the adult nervous system. Studying the mechanisms that underlie sensory cell regeneration affords a unique opportunity to learn how to control and enhance neuronal regeneration at the cellular and molecular levels. Moreover, the information gained may translate into clinically useful information for regenerating neurons lost in the central nervous system following stroke, trauma, and neurodegenerative diseases.

Sensory systems show remarkable differences in the degree to which they are able to generate new sensory cells. In the mammalian hearing organ, the number of sensory hair cells is established early in development, and, following injury, are not replaced. In birds, by contrast, hair cell regeneration and restored auditory function is observed following injury. Scientists are examining the interaction between extracellular factors and molecules within the cell which determine whether or not a supporting cell in the inner ear can divide and generate a new hair cell. This regulatory process is fundamental to growth regulation in all organ systems, and is called cell cycle regulation.

NIDCD-supported scientists have examined the importance of one cell cycle regulatory protein, cyclin-dependent kinase inhibitor 27 (p27Kip1), an enzyme shown to regulate cellular proliferation by interrupting the cell cycle in other model systems. During development of the organ of Corti, as cells undergo terminal differentiation to become hair cells, they no longer express p27Kip1. By contrast, supporting cells, which are potential hair cell precursors, continue to express this enzyme. In mice where scientists have inactivated the p27Kip1 gene, there is an increased number of hair cells and supporting cells in the developing cochlea, and hair cells continue to differentiate from proliferating supporting cells in postnatal animals and adults. In contrast, normal mice with a functional p27Kip1 gene show no increases in hair cell number and no new hair cells are produced after birth. These exciting results demonstrate for the first time that hair cell regeneration is possible in mammals, and that cell cycle regulation is important in controlling hair cell regeneration.

In contrast to hair cells in the mammalian inner ear, olfactory sensory neurons are continuously replaced from a stem cell population in the nasal epithelium and the new neurons regrow axons that connect only to appropriate targets in the brain. NIDCD-supported scientists have shown that olfactory neuronal regeneration is regulated by the production of a secreted growth regulatory molecule called bone morphogenetic protein 4. Knowledge gained from studying regulation of regeneration of olfactory neurons may provide insight into the more general issue of neuronal regeneration in the brain.

Olfactory Receptor Proteins Have a Dual Function
Researchers estimate that about 1000 genes, or approximately one percent of our genetic information, is devoted to olfactory receptor genes, making this among the largest gene families thus far identified in mammals. These genes encode the proteins that bind odorants, which trigger a cascade of events within the olfactory neuron resulting in a signal being sent to the brain. Scientists are beginning to understand how olfactory signals are processed in the central nervous system. Each of the millions of olfactory neurons selects only one of this large receptor gene family for expression. All olfactory neurons expressing the same receptor send these axons to the same targets in the brain. An NIDCD-supported scientist has determined molecular mechanisms that regulate this remarkable targeting specificity by showing that the olfactory receptor protein itself appears to play a role in guiding axons to precise targets within the brain. The olfactory receptor expressed by a sensory neuron would appear to provide an address that guides the growing axon to a defined target. Genetic manipulation of the receptor that is expressed results in a new address and a different pattern of connections. These studies reveal a new molecular mechanism for determining connections between neurons in the nervous system, which may play an important role in the development of the central nervous system.

The activities of the National Institute on Deafness and Other Communication Disorders are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan which was transmitted to Congress on September 30, 1997. NIH's performance targets in the Plan are partially a function of resource levels requested in the President's Budget and could change based upon final Congressional Appropriations action. NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.

My colleagues and I will be happy to respond to any questions you may have.

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