Prenatal augmented auditory stimulation and visual system development: Effects of timing on intersensory organization

This study investigated the effects of augmented prenatal auditory stimulation on postnatal visual responsivity and neural organization in bobwhite quail (Colinus virginianus). I delivered conspecific embryonic vocalizations before, during, or after the development of a multisensory, midbrain audiovisual area, the optic tectum. Postnatal simultaneous choice tests revealed that hatchlings receiving augmented auditory stimulation during optic tectum development as embryos failed to show species-typical visual preferences for a conspecific maternal hen 72 hours after hatching. Auditory simultaneous choice tests showed no hatchlings had deficits in auditory function in any of the groups, indicating deficits were specific to visual function. ZENK protein expression confirmed differences in the amount of neural plasticity in multiple neuroanatomical regions of birds receiving stimulation during optic tecturn development, compared to unmanipulated birds. The results of these experiments support the notion that the timing of augmented prenatal auditory stimulation relative to optic tectum development can impact postnatal perceptual organization in an enduring way.^

The role of temporal synchrony in the facilitation of perceptual learning during prenatal development

This study explored the critical features of temporal synchrony for the facilitation of prenatal perceptual learning with respect to unimodal stimulation using an animal model, the bobwhite quail. The following related hypotheses were examined: (1) the availability of temporal synchrony is a critical feature to facilitate prenatal perceptual learning, (2) a single temporally synchronous note is sufficient to facilitate prenatal perceptual learning, with respect to unimodal stimulation, and (3) in situations where embryos are exposed to a single temporally synchronous note, facilitated perceptual learning, with respect to unimodal stimulation, will be optimal when the temporally synchronous note occurs at the onset of the stimulation bout. To assess these hypotheses, two experiments were conducted in which quail embryos were exposed to various audio-visual configurations of a bobwhite maternal call and tested at 24 hr after hatching for evidence of facilitated prenatal perceptual learning with respect to unimodal stimulation. Experiment 1 explored if intermodal equivalence was sufficient to facilitate prenatal perceptual learning with respect to unimodal stimulation. A Bimodal Sequential Temporal Equivalence (BSTE) condition was created that provided embryos with sequential auditory and visual stimulation in which the same amodal properties (rate, duration, rhythm) were made available across modalities. Experiment 2 assessed: (a) whether a limited number of temporally synchronous notes are sufficient for facilitated prenatal perceptual learning with respect to unimodal stimulation, and (b) whether there is a relationship between timing of occurrence of a temporally synchronous note and the facilitation of prenatal perceptual learning. Results revealed that prenatal exposure to BSTE was not sufficient to facilitate perceptual learning. In contrast, a maternal call that contained a single temporally synchronous note was sufficient to facilitate embryos’ prenatal perceptual learning with respect to unimodal stimulation. Furthermore, the most salient prenatal condition was that which contained the synchronous note at the onset of the call burst. Embryos’ prenatal perceptual learning of the call was four times faster in this condition than when exposed to a unimodal call. Taken together, bobwhite quail embryos’ remarkable sensitivity to temporal synchrony suggests that this amodal property plays a key role in attention and learning during prenatal development.

Prenatal environmental exposure and neurodevelopmentally important gene expression in malformed brain tissue from pediatric intractable epilepsy patients

The primary objective of this proposal was to determine whether mitochondrial oxidative stress and variation in a particular mtDNA lineage contribute to the risk of developing cortical dysplasia and are potential contributing factors in epileptogenesis in children. The occurrence of epilepsy in children is highly associated with malformations of cortical development (MCD). It appears that MCD might arise from developmental errors due to environmental exposures in combination with inherited variation in response to environmental exposures and mitochondrial function. Therefore, it is postulated that variation in a particular mtDNA lineage of children contributes to the effects of mitochondrial DNA damage on MCD phenotype. Quantitative PCR and dot blot were used to examine mitochondrial oxidative damage and single nucleotide polymorphism (SNP) in the mitochondrial genome in brain tissue from 48 pediatric intractable epilepsy patients from Miami Children’s Hospital and 11 control samples from NICHD Brain and Tissue Bank for Developmental Disorders. Epilepsy patients showed higher mtDNA copy number compared to normal health subjects (controls). Oxidative mtDNA damage was lower in non-neoplastic but higher in neoplastic epilepsy patients compared to controls. There was a trend of lower mtDNA oxidative damage in the non-neoplastic (MCD) patients compared to controls, yet, the reverse was observed in neoplastic (MCD and Non-MCD) epilepsy patients. The presence of mtDNA SNP and haplogroups did not show any statistically significant relationships with epilepsy phenotypes. However, SNPs G9804A and G9952A were found in higher frequencies in epilepsy samples. Logistic regression analysis showed no relationship between mtDNA oxidative stress, mtDNA copy number, mitochondrial haplogroups and SNP variations with epilepsy in pediatric patients. The levels of mtDNA copy number and oxidative mtDNA damage and the SNPs G9952A and T10010C predicted neoplastic epilepsy, however, this was not significant due to a small sample size of pediatric subjects. Findings of this study indicate that an increase in mtDNA content may be compensatory mechanisms for defective mitochondria in intractable epilepsy and brain tumor. Further validation of these findings related to mitochondrial genotypes and mitochondrial dysfunction in pediatric epilepsy and MCD may lay the ground for the development of new therapies and prevention strategies during embryogenesis.

Elevated progesterone in yolk as a moderator of prenatal and postnatal auditory learning in bobwhite quail

Recent studies have established that yolk hormones of maternal origin have significant effects on the physiology and behavior of offspring in birds. Herrington (2012) demonstrated that an elevation of progesterone in yolk elevates emotional reactivity in bobwhite quail neonates. Chicks that hatched from progesterone treated eggs displayed increased latency in tonic immobility and did not emerge as quickly from a covered location into an open field compared to control groups. For the present study, three experimental groups were formed: chicks hatched from eggs with artificially elevated progesterone (P), chicks hatched from an oil-vehicle control group (V), and chicks hatched from a non-manipulated control group (C). Experiment 1 examined levels of progesterone with High Performance Liquid Chromatography/tandem Mass Spectroscopy (HPLC/MS) from prenatal day 1 to prenatal day 17 in bobwhite quail egg yolk. In Experiment 2, bobwhite quail embryos were passively exposed to an individual maternal assembly call for 24 hours prior to hatching. Chicks were then tested individually for their preference between the familiarized call and a novel call at 24 and 48 hours following hatching. For Experiment 3, newly hatched chicks were exposed to an individual maternal assembly call for 24-hrs. Chicks were then tested for their preference for the familiarized call at 24 and 48-hrs after hatch. Results of Experiment 1 showed that yolk progesterone levels were significantly elevated in treated eggs and were present in the egg yolk longer into prenatal development than the two control groups. Results from Experiment 2 indicated that chicks from the P group failed to demonstrate a preference for the familiar bobwhite maternal assembly call at 24 or 48-hrs after hatch following 24-hrs of prenatal exposure. In contrast, chicks from the C and V groups demonstrated a significant preference for the familiarized call. In Experiment 3, chicks from the P group showed an enhanced preference for the familiarized bobwhite maternal call compared to chicks from the C and V groups at 24 and 48-hrs after hatch. The results of these experiments suggest that elevated maternal yolk hormone levels in pre-incubated bobwhite quail eggs can influence auditory perceptual learning in embryos and neonates.^

The Role of Temporal Synchrony in the Facilitation of Perceptual Learning during Prenatal Development

This study explored the critical features of temporal synchrony for the facilitation of prenatal perceptual learning with respect to unimodal stimulation using an animal model, the bobwhite quail. The following related hypotheses were examined: (1) the availability of temporal synchrony is a critical feature to facilitate prenatal perceptual learning, (2) a single temporally synchronous note is sufficient to facilitate prenatal perceptual learning, with respect to unimodal stimulation, and (3) in situations where embryos are exposed to a single temporally synchronous note, facilitated perceptual learning, with respect to unimodal stimulation, will be optimal when the temporally synchronous note occurs at the onset of the stimulation bout. To assess these hypotheses, two experiments were conducted in which quail embryos were exposed to various audio-visual configurations of a bobwhite maternal call and tested at 24 hr after hatching for evidence of facilitated prenatal perceptual learning with respect to unimodal stimulation. Experiment 1 explored if intermodal equivalence was sufficient to facilitate prenatal perceptual learning with respect to unimodal stimulation. A Bimodal Sequential Temporal Equivalence (BSTE) condition was created that provided embryos with sequential auditory and visual stimulation in which the same amodal properties (rate, duration, rhythm) were made available across modalities. Experiment 2 assessed: (a) whether a limited number of temporally synchronous notes are sufficient for facilitated prenatal perceptual learning with respect to unimodal stimulation, and (b) whether there is a relationship between timing of occurrence of a temporally synchronous note and the facilitation of prenatal perceptual learning. Results revealed that prenatal exposure to BSTE was not sufficient to facilitate perceptual learning. In contrast, a maternal call that contained a single temporally synchronous note was sufficient to facilitate embryos’ prenatal perceptual learning with respect to unimodal stimulation. Furthermore, the most salient prenatal condition was that which contained the synchronous note at the onset of the call burst. Embryos’ prenatal perceptual learning of the call was four times faster in this condition than when exposed to a unimodal call. Taken together, bobwhite quail embryos’ remarkable sensitivity to temporal synchrony suggests that this amodal property plays a key role in attention and learning during prenatal development.

Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes

Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR).

Effects of Prenatal and Early Postnatal Exposure to Aversive Stimuli on Fearfulness and Exploratory Behavior in Bobwhite Qauil Neonates (Colinus virginianus)

Neophobia, the fear of novelty, is a behavioral trait found across a number of animal species, including humans. Neophobic individuals perceive novel environments and stimuli to have aversive properties, and exhibit fearful behaviors when presented with non-familiar situations. The present study examined how early life exposure to aversive novel stimuli could reduce neophobia in bobwhite quail chicks. Experiment 1 exposed chicks to a novel auditory tone previously shown to be aversive to naïve chicks (Suarez, 2012) for 24 hours immediately after hatching, then subsequently tested them in the presence of the tone within a novel maze task. Postnatally exposed chicks demonstrated decreased fearfulness compared to naïve chicks, and behaved more similarly to chicks tested in the presence of a known attractive auditory stimulus (a bobwhite maternal assembly call vocalization). Experiment 2 exposed chicks to the novel auditory tone for 24 hours prenatally, then subsequently tested them within a novel maze task. Prenatally exposed chicks showed decreased fearfulness to a similar degree as those postnatally exposed, revealing that both prenatal and postnatal exposure methods are capable of decreasing fear of auditory stimuli. Experiment 3 exposed chicks to a novel visual stimulus for 24 hours postnatally, then subsequently tested them within a novel emergence box / T-maze apparatus. Chicks exposed to the visual stimulus showed decreased fearfulness compared to naïve chicks, thereby demonstrating the utility of this method across sense modalities. Experiment 4 assessed whether early postnatal exposure to one novel stimulus could generalize and serve to decrease fear of novelty when chicks were tested in the presence of markedly different stimuli. By combining the methods of Experiments 1 and 3, this experiment revealed that chicks exposed to one type of stimulus (auditory or visual) demonstrated decreased fear when subsequently tested in the presence of the opposite type of novel stimulus. These results suggest that experience with novel stimuli can moderate the extent to which neophobia will develop during early development.

The Effect of Prenatal Auditory Enrichment on Perceptual Narrowing in Bobwhite Quail Neonates

The development of species-typical perceptual preferences has been shown to depend on a variety of socially and ecologically derived sensory stimulation during both the pre- and postnatal periods. The prominent mechanism behind the development of these seemingly innate tendencies in young organisms has been hypothesized to be a domain-general pan-sensory selectivity process referred to as perceptual narrowing, whereby regularly experienced sensory stimuli are honed in upon, while simultaneously losing the ability to effectively discriminate between atypical or unfamiliar sensory stimulation. Previous work with precocial birds has been successful in preventing the development of species-typical perceptual preferences by denying the organism typical levels of social and/or self-produced stimulation. The current series of experiments explored the mechanism of perceptual narrowing to assess the malleability of a species-typical auditory preference in avian embryos. By providing a variety of different unimodal and bimodal presentations of a mixed-species vocalizations at the onset of prenatal auditory function, the following project aimed to 1) keep the perceptual window from narrowing, thereby interfering with the development of a species-typical auditory preference, 2) investigate how long differential prenatal stimulation can keep the perceptual window open postnatally, 3) explore how prenatal auditory enrichment effected preferences for novelty, and 4) assess whether prenatal auditory perceptual narrowing is affected by modality specific or amodal stimulus properties during early development. Results indicated that prenatal auditory enrichment significantly interferes with the emergence of a species-typical auditory preference and increases openness to novelty, at least temporarily. After accruing postnatal experience in an environment rich with species-typical auditory and multisensory cues, the effect of prenatal auditory enrichment rapidly was found to rapidly fade. Prenatal auditory enrichment with extraneous non-synchronous light exposure was shown to both keep the perceptual narrowing window open and impede learning in the postnatal environment, following hatching. Results are discussed in light of the role experience plays in perceptual narrowing during the perinatal period.

Effects of Altered Prenatal Sensory Stimulation on Postnatal Contingency Learning in Bobwhite Quail Neonates (Colinus Virginianus)

Preterm infants are exposed to high levels of modified early sensory experience in the Neonatal Intensive Care Unit (NICU). Reports that preterm infants show deficits in contingency detection and learning when compared to full-term infants (Gekoski, Fagen, & Pearlman, 1984; Haley, Weinberg, & Grunau, 2006) suggest that their exposure to atypical amounts or types of sensory stimulation might contribute to deficits in these critical skills. Experimental modifications of sensory experience are severely limited with human fetuses and preterm infants, and previous studies with precocial bird embryos that develop in ovo have proven useful to assess the effects of modified perinatal sensory experience on subsequent perceptual and cognitive development. In the current study, I assessed whether increasing amounts of prenatal auditory or visual stimulation can interfere with quail neonates’ contingency detection and contingency learning in the days following hatching. Results revealed that augmented prenatal visual stimulation prior to hatching does not disrupt the ability of bobwhite chicks to recognize and prefer information learned in a contingent fashion, whereas augmented prenatal auditory stimulation disrupted the ability of chicks to benefit from contingently presented information. These results suggest that specific types of augmented prenatal stimulation that embryos receive during late prenatal period can impair the ability to learn and remember contingently presented information. These results provide testable developmental hypotheses, with the goal of improving the developmental care and management of preterm neonates in the NICU setting.

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries.

SETTING: Eight European countries.

POPULATION: 14.8 million births 1990-2009; 2.89% multiple births.

METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.

MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.

STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time.

RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).

CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Fetal Movements in late Pregnancy : Categorization, Self-assessment, and Prenatal Attachment in relation to women’s experiences

Aim: To explore how pregnant women experience fetal movements in late pregnancy. Specific aims were:  to study women’s experiences during the time prior to receiving news that their unborn baby had died in utero (I), to investigate women’s descriptions of fetal movements (II), investigate the association between the magnitude of fetal movements and level of prenatal attachment (III), and to study women’s experiences using two different self-assessment methods (IV). Methods: Interviews, questionnaires, and observations were used. Results: Premonition that something had happened to their unborn baby, based on a lack of fetal movements, was experienced by the participants. The overall theme “something is wrong” describes the women’s insight that the baby’s life was threatened (I). Fetal movements that were sorted into the domain “powerful movements” were perceived in late pregnancy by 96 % of the participants (II). Perceiving frequent fetal movements on at least three occasions per 24 hours was associated with higher scores of prenatal attachment in all the three subscales on PAI-R. The majority (55%) of the 456 participants reported average occasions of frequent fetal movements, 26% several occasions and 18% reported few occasions of frequent fetal movements, during the current gestational week.  (III). Only one of the 40 participants did not find at least one method for monitoring fetal movements suitable. Fifteen of the 39 participants reported a preference for the mindfetalness method and five for the count-to-ten method. The women described the observation of the movements as a safe and reassuring moment for communication with their unborn baby (IV). Conclusion:  In full-term and uncomplicated pregnancies, women usually perceive fetal movements as powerful. Furthermore, women in late pregnancy who reported frequent fetal movements on several occasions during a 24-hour period seem to have a high level of prenatal attachment. Women who used self-assessment methods for monitoring fetal movements felt calm and relaxed when observing the movements of their babies. They had a high compliance for both self-assessment methods. Women that had experienced a stillbirth in late pregnancy described that they had a premonition before they were told that their baby had died in utero. 

Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Twins prematurity--the influence of prenatal surveillance

OBJECTIVE: To evaluate the influence of the local prenatal surveillance of twin pregnancies in the obstetrical results. METHODS: A prospective cohort study of multiple pregnancies delivered over a period of 16 years in a tertiary centre was conducted. In this study 861 twin pregnancies were included. They were compared for obstetric complications, gestational age at delivery, mode of delivery and birthweight, according to the place of the surveillance. RESULTS: Of the 861 cases examined, the following obstetric complications were significantly different: metrorrhagia (p = 0.039), infections (p < 0.001), HELLP (p = 0.007), PROMPT (p < 0.001) and fetal death (p = 0.024). The mode of delivery was similar but occurred mostly ≤32 weeks (p < 0.001), the birthweight was mostly <2000 g and occurred more NICU admission (p < 0.001) when surveillance was outside the MPC-MDM. CONCLUSION: Our results demonstrate the crucial importance of prenatal surveillance be carried in a differentiated referral centers with specific/strict protocols or the urgent implementation of same protocols in all other places of surveillance, since this straight surveillance greatly reduces the occurrence of prenatal complications, mainly PROMPT, PTD.

Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/β cell ratio and subsequent insulin secretion

Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P=0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P=0.001), sustained into adolescence (P=0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P=0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P=0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P=0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells.