William Fifer - US grants

The current literature on infant development points to a continually growing appreciation of the perceptual and learning capabilities of the human newborn. Research has shown the neonate is sensorially precocial and capable of demonstrating perceptual preferences. However, relatively little is known about the sensory and social receptivity of the rapidly increasing population of preterm infants. In our laboratory, using a choice procedure, we have shown that infants as young as one day old can discriminate, and actually prefer to listen to, their own mother's voice versus another female's voice. The general goal of this proposal is to make a substantial contribution to the body of knowledge detailing the behavioral and sensory functions of health fullterm newborns and those infants born prior to their expected date of birth. The specific goals are to characterize the response of full- and pre-term infants to the maternal voice and to develop techniques for the assessment of individual differences in this response as a function of gestational age and perinatal experience. Having identified differences in the nature of the neonate's response to the maternal voice, the final goal of this proposal will be to test whether postnatal experience with mother's voice will alter the response of the hospitalized premature infant to vocal stimulation.

Newborn infants prefer the sound of their own mother's versus another mother's voice. Little is known about the development of this selective response and the cues which are salient to the infant in identification of mother's voice. Intrauterine experience is a likely precursor, and the response may reflect a preference for a familiar sound or perceptual bias resulting from early exposure. Recordings made in the amniotic environment indicate emergence mothers's voice over other voices against a background of vascular and digestive noise. In a recent study using a nonnutritive sucking choice procedure, two-day-olds preferred the sound of mother's simulated in utero voice versus a normal recording of her voice. There was evidence to suggest that this preference may reverse in the first postnatal week with extrauterine experience (Moon & Fifer, 1986). The main goal of the proposed research is to investigate early perception of the speech signal, and in particular, to characterize responding to three cues which are likely to be salient to newborns. The three cues are prosody filtering, and the unique qualities of mother's vocal tract. These cue will be systematically combined in pairs of stimuli which are expected to elicit a preference by the infant. A change in a salient cue is expected to result in a change in preference. Conclusions about the relative salience of the three cues will be based upon results from individual experiments, and inferences will be made from patterns of results. A further goal is to investigate the generality of responding to cues in the intrauterine speech signal. Non-speech acoustic stimuli will be presented with intra- versus etrauterine features. The results of the proposed project will have implications for early speech perception and for early cognitive capacities.

DESCRIPTION (Adapted from the Applicant's Description):It has long been accepted that prolonged prenatal insult and subsequent fetal compromise can alter the normal development of the fetal CNS in ways that produce vulnerability to subsequent neurological impairment. Two global issues addressed in the proposed studies are: development of new assessment methodologies in the perinatal period, and evaluation of the efficacy of these methodologies for predicting impairments in neurologic development and/or SIDS. These assessments will be conducted in an urban low-SES population presenting additional risk factors for poor neurological outcome and SIDS, and in a Native American population on the Pine Ridge Reservation in South Dakota which is at unusually high risk for SIDS and other manifestations of neurologic damage. In one set of studies the investigators will apply new assessment methods for evaluating the integrity of cardiorespiratory control systems in the fetus, track the maturation of these measures through the perinatal period, and then determine their relationship to outcome at one year of age. Another series of experiments will focus on the early development of reflex cardiovascular adjustment to postural manipulations, cardiorespiratory responses to salient auditory stimuli, and cortical evoked responses. There are two facets to the strategy for assessing the sensitivity of the measures. The first is to test the ability of the measures to discriminate risk groups (maternal smoking and anemia) that vary in their degree of compromise to the fetus and newborn. The second will be to determine whether the measured profiles of physiological development predict neurologic outcome of the study populations assessed at one year of age. There are three primary Aims of the proposed studies. Aim 1. To determine whether indices of neural regulation of cardiorespiratory activity measured in the perinatal period will distinguish populations at risk for developing neurologic disorders and/or SIDS. Aim 2. To determine whether a profile of state dependent evoked cardiorespiratory and/or cortical responses made through the perinatal period will distinguish populations of fetuses and infants at-risk for developing neurologic disorders and/or SIDS. Aim 3. To determine whether indices of neural regulation of cardiorespiratory activity measured in Native American newborns will distinguish those infants at greatest risk for developing neurologic disorders and/or SIDS.

perinatal; epidemiology; human population study; nervous system disorder; disease /disorder proneness /risk; sudden infant death syndrome; early diagnosis; urban poverty area; clinical research; human subject;

DESCRIPTION (Adapted from the Applicant's Description):It has long been accepted that prolonged prenatal insult and subsequent fetal compromise can alter the normal development of the fetal CNS in ways that produce vulnerability to subsequent neurological impairment. Two global issues addressed in the proposed studies are: development of new assessment methodologies in the perinatal period, and evaluation of the efficacy of these methodologies for predicting impairments in neurologic development and/or SIDS. These assessments will be conducted in an urban low-SES population presenting additional risk factors for poor neurological outcome and SIDS, and in a Native American population on the Pine Ridge Reservation in South Dakota which is at unusually high risk for SIDS and other manifestations of neurologic damage. In one set of studies the investigators will apply new assessment methods for evaluating the integrity of cardiorespiratory control systems in the fetus, track the maturation of these measures through the perinatal period, and then determine their relationship to outcome at one year of age. Another series of experiments will focus on the early development of reflex cardiovascular adjustment to postural manipulations, cardiorespiratory responses to salient auditory stimuli, and cortical evoked responses. There are two facets to the strategy for assessing the sensitivity of the measures. The first is to test the ability of the measures to discriminate risk groups (maternal smoking and anemia) that vary in their degree of compromise to the fetus and newborn. The second will be to determine whether the measured profiles of physiological development predict neurologic outcome of the study populations assessed at one year of age. There are three primary Aims of the proposed studies. Aim 1. To determine whether indices of neural regulation of cardiorespiratory activity measured in the perinatal period will distinguish populations at risk for developing neurologic disorders and/or SIDS. Aim 2. To determine whether a profile of state dependent evoked cardiorespiratory and/or cortical responses made through the perinatal period will distinguish populations of fetuses and infants at-risk for developing neurologic disorders and/or SIDS. Aim 3. To determine whether indices of neural regulation of cardiorespiratory activity measured in Native American newborns will distinguish those infants at greatest risk for developing neurologic disorders and/or SIDS.

The purpose of the competing renewal of this conference travel grant is to continue to facilitate student/postdoctoral involvement (both current members and newer graduate students who are potential members) in the International Society for Developmental Psychobiology meetings. We are requesting partial support of the travel expenses of 30 predoctoral and 20 postdoctoral students for attendance at the annual meetings of the International Society for Developmental Psychobiology over the next five years. The 2000 ISDP meeting will be held in New Orleans, LA, just prior to the Society for Neuroscience meeting. The previous two meetings (ISDP 1998 in Orleans, France and ISDP, 1999 in Coral Gables, FL) have been enormously successful, due in no small part to the travel grants provided by NIH that provided partial support for graduate students and postdoctoral fellows to attend these meetings. At the 1999 meeting, we were able to provide partial travel support for 41 students/postdoctoral fellows, which resulted in the highest student attendance of any ISDP meeting in the past five years. In addition, this funding enabled us to begin a new tradition at ISDP; travel award winners were invited to present select data in a "single-slide" 5-min talk. Reactions to these presentations were overwhelmingly enthusiastic from both students and senior scientists. Students and postdoctoral fellows are the lifeblood of the society, and it is critical, especially in a small society such as this, to foster a high level of student participation. Indeed, many of the active members of ISDP who are now at or approaching the level of professor first became involved with the Society as students, and many gave their first research presentation at an ISDP meeting. Student travel support remains a critical issue for our society, given the limited nature of travel funds available. Continuation of travel support from NIH will have a major impact on our ability to bring students and postdoctoral fellows to the meeting. Furthermore, support for student travel will enable us to use the limited funds in the ISDP account in ways that will increase the impact of such a grant even further. For example, last year Society funds were utilized to provide partial travel support for four foreign graduate students. The present proposal requests five years of support, to continue to provide funds for partial support of travel for student and postdoctoral fellows to the ISDP annual meetings. Obtaining multiple year support will help to establish a culture of attendance at the ISDP meetings among graduate students at various universities, which will prolong the impact of the grant long after the period of support requested.

The overall goals of our project remain unchanged from our original application: to carry out a program of research to develop non-invasive assessment tools, grounded in known physiological mechanisms, in infants at risk for SIDS and other developmental disorders. To continue this mission we have expanded our approach and our multidisciplinary team of perinatal researchers in order to develop new risk indices as early as possible in the life of the fetus and young infant. Over the next Ave years we will be assessing approximately 80 infants/year In the Northern Plains and 100 subjects/year in NYC from the late fetal through the early newborn period. In these studies we propose to incorporate more direct measures of CNS maturation during sleep, as well as more sophisticated analyses of autonomic nervous system regulation in both the fetus and infant in healthy and at-risk populations. Our physiological studies focus on testing both healthy term and at-risk, prematurely born infants in response to physiological challenges associated with changes in sleep state, prone vs supine sleep positions, and orthostatic tilt. These studies are conducted prior to and during the age range of greatest vulnerability for SIDS. In addition to our battery of existing measurements of respiration, heart rate, blood pressure, movement, EEG and temperature, we propose to incorporate new state of the art measures of venous return and tissue perfusion, as we believe these parameters will provide more direct information about the physiological forces that drive responses to alterations in tilt and sleep position. In addition, we will expand our use of fetal ECG monitoring to more comprehensively assess autonomic and cardiac function in the late term fetus. Specifically, with the Monica abdominal fECG device we will investigate maternal/fetal ECG interactions, the effect of uterine activity on fetal heart rate, incidence and variation in fetal arrhythmias, fetal movement and heart rate coupling, patterns of heart rate variability and fetal heart rate response to sound. This new technology will also allow access to-markers of perinatal autonomic function in both time and frequency domains, previously only accessible in the infant. We also propose to augment our autonomic challenges to include investigation of arousal and learning We have found an important cortical component to tilt and a strong relationship of cortical power and synchrony with postconceptional age and later outcome. We have also developed analytic toots that can quantify arousal, i.e., cortical activation, in response to sensory stimulation and while learning during Sleep. We propose to extend our investigations of cortical and cerebellar markers of reactivity and learning during sleep in both healthy and high risk premature infants prior to discharge from the hospital and at one month of age. We predict that altered patterns of electrocortical synchrony will be associated with adverse prenatal exposures, both in premature infants and in the high risk sample from the Northern Plains. In these populations we will continue to measure local and distal coherence, as well as high frequency spectral power, parameters we have shown to be altered during tilts and which are affected by sleep positions. The additional EEG measures will provide more comprehensive estimates of individual physiological trajectories following adverse exposures. Consistent with our initial proposal we will export new comprehensive assessment techniques developed in our Columbia laboratories to assess a vulnerable population (Native Amencans in the Northern Plains). This work, which in past years was conducted on the Pine Ridge Indian Reservation in South Dakota, was curtailed due to budget cuts in our last application. However, we now plan to merge our efforts with those of another NICHD/NIAAA study being conducted by the PASS network in Rapid City, S.D: In these studies, we will measure EEG and autonomic activity as a function of prenatal risk factors In one month old Infants during sleep in both prone and supine positions and in response to a tilt challenge. In summary, our primary hypotheses focus on testing how known risk factors for SIDS premature birth, sleep position, prenatal exposures) alter physiological function in the fetus and infant Our long-term objectives are to elucidate physiologic mechanisms that underlie SIDS and to develop, age-appropriate, non-invasive tests that will identify infants who are at the greatest risk. These primary hypotheses and goals remain as stated in our original application.

DESCRIPTION (provided by applicant): The purpose of the present competing renewal of our conference travel grant is to continue to facilitate student/postdoctoral fellow involvement (both current members and newer graduate students who are potential members) in the International Society for Developmental Psychobiology (ISDP) meetings. The mission of ISDP is to promote and encourage research on the development of behavior in all organisms, including humans, with special attention to the effects of biological factors operating at any level of organization. The epigenetic underpinnings of both normal and abnormal development are targets of study. We are requesting partial support of the travel expenses of 30 pre-doctoral and 20 postdoctoral students for attendance at the annual meetings of the ISDP over the next 5 years. The 2005 ISDP meeting will be held in Washington, DC, just prior to the Society for Neuroscience meeting. Our previous two meetings (2003 in New Orleans, LA and 2004 in Aix en Provence, France) have been enormously successful, due in no small part to the travel grants from NIH that provided partial support for graduate students and postdoctoral fellows to travel to these meetings. Since the 1999 meeting, we have provided partial travel support for 40 or more students/postdoctoral fellows. Student attendance at ISDP meetings has grown steadily in the past 5 years. In addition, this funding enabled us to begin a new tradition at ISDP;travel award winners were invited to present select data in a "single slide" 5-min talk. Reactions to these presentations were overwhelmingly enthusiastic from both students and senior scientists. Students and postdoctoral fellows are the lifeblood of our society. It is critical in a small society such as ours to foster a high level of student participation. Indeed, many of the senior members of ISDP first became involved in the Society as students. Many gave their first research presentation at an ISDP meeting. Student travel support remains a critical issue for our society, given the limited nature of travel funds available. Continuation of travel support from NIH will have a major impact on our ability to bring students and postdoctoral fellows to this meeting. Furthermore, support for student travel will enable us to use the limited funds in the ISDP account in ways that will increase the impact of such a grant even further. For example, we are able to provide partial travel support to bring foreign graduate students to meetings and facilitate interactions with US members. The present proposal requests 5 years of support, to continue to provide funds for partial support of travel for student and postdoctoral fellows to the ISDP annual meetings. Obtaining multiple year support will encourage a culture of attendance at the ISDP meetings among graduate students at various universities, which will prolong the impact of the grant long after the period of support requested.

DESCRIPTION (provided by applicant): This application is in response to a Letter of Invitation (LOI-HD-05-111) to conduct community-linked studies to investigate the role of prenatal alcohol exposure in the risk for SIDS, stillbirth and FAS, and to determine how these different outcomes are inter-related. The proposed research will be conducted by the investigators the Prenatal Alcohol, SIDS, and Stillbirth (PASS) Research Network in a cooperative agreement with NICHD and NIAAA. This research involves the collaboration of: 1) two comprehensive clinical sites serving populations that are high risk for prenatal alcohol exposure, SIDS, and stillbirth, i.e. the American Indians in the Northern Plains and the Cape Coloured in Cape Town, South Africa;2) a central Developmental Biology and Pathology Center (DBPC);3) a central Data Coordinating and Analysis Center (DCAC);4) a central Physiology Assessment Center (PAC);and 5) program scientists and officers at the NICHD and NIAAA. This particular application pertains to the Physiology Assessment Center (PAC) of the PASS Network. The experimental design involves a prospective study of 12,000 pregnancies, and two retrospective, autopsy-based studies of SIDS and stillbirth. The long-term goals of the SAFE PASSAGE STUDY are to decrease fetal and infant mortality and improve child health in communities at high risk for prenatal maternal alcohol consumption. The Specific Aims of the Network are as follows: 1. To determine the association between prenatal alcohol exposure and the risk for SIDS and;2. To determine the role of the timing, pattern, and amount of prenatal alcohol exposure and other environmental factors in the risk for morbidity and mortality in early human life;3. To determine the role of specific genes in modifying the risk for morbidity and mortality in early life that is associated with prenatal alcohol exposure;4. To determine the role of alcohol exposure during pregnancy, and interactions among alcohol exposure and environmental and genetic modifiers, in altering profiles of autonomic activity of the fetus and infant, and neurobehavioral outcomes in the infant;5. To determine the role of maternal alcohol exposure, as influenced by specific environmental and genetic factors, in the impairment of placental function, and thereby the increased risk for fetal and/or infant morbidity and mortality;and 6. To determine abnormalities in key neurotransmitter systems in the brains of fetuses and/or infants that convey risk for sudden death, and to determine the role of prenatal alcohol exposure, as influenced by specific environmental and genetic factors, in their pathogenesis. The mission of the PAC is to conduct sophisticated analyses of physiologic control based on the recordings obtained from subjects enrolled in the SAFE PASSAGE STUDY.