From early markers to neuro-developmental mechanisms of autism

A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions

The role of self-touch experience in the formation of the self

The human self has many facets: there is the physical body and then there are different concepts or representations supported by processes in the brain such as the ecological, social, temporal, conceptual, and experiential self. The mechanisms of operation and formation of the self are, however, largely unknown. The basis is constituted by the ecological or sensorimotor self that deals with the configuration of the body in space and its action possibilities. This self is prereflective, prelinguistic, and initially perhaps even largely independent of visual inputs. Instead, somatosensory (tactile and proprioceptive) information both before and after birth may play a key part. In this paper, we propose that self-touch experience may be a fundamental mechanisms to bootstrap the formation of the sensorimotor self and perhaps even beyond. We will investigate this from the perspectives of phenomenology, developmental psychology, and neuroscience. In light of the evidence from fetus and infant development, we will speculate about the possible mechanisms that may drive the formation of first body representations drawing on self-touch experience

Mother’s depression at childbirth does not contribute to the effects of antenatal depression on neonate’s behavioral development

Background: Maternal depression is a worldwide phenomenon that has been linked to adverse developmental outcomes in neonates. Aims: To study the effect of antenatal depression (during the third trimester of pregnancy) on neonate behavior, preference, and habituation to both the mother and a stranger’s face/voice. To analyze mother’s depression at childbirth as a potential mediator or moderator of the relationship between antenatal depression and neonate behavioral development. Method: A sample of 110 pregnant women was divided in 2 groups according to their scores on the Edinburgh Postnatal Depression Scale during pregnancy (EPDS; ≥10, depressed; <10, non-depressed). In the first 5 days after birth, neonatal performance on the Neonatal Behavioral Assessment Scale (NBAS) and in the ‘Preference and habituation to the mother’s face/voice versus stranger’ paradigm was assessed; each mother filled out an EPDS. Results: Neonates of depressed pregnant women, achieved lower scores on the NBASs (regulation of state, range of state, and habituation); did not show a visual/auditory preference for the mother’s face/voice; required more trials to become habituated to the mother’s face/voice; and showed a higher visual/auditory preference for the stranger’s face/voice after habituation compared to neonates of non-depressed pregnant women. Depression at childbirth does not contribute to the effect of antenatal depression on neonatal behavioral development. Conclusion: Depression even before childbirth compromises the neonatal behavioral development. Depression is a relevant issue and should be addressed as a routine part of prenatal health care.The study was financed by “FCT – Fundação para a Ciência e Tecnologia” (Grant SFRH/BD/21956/2005), Ministry of Science, Technology and Higher Education in the scope of POCI 2010. Advanced training for science – measure IV.3. Reimbursed by the European Social Fund – Operational Human Potential Program (POPH) – and by National Funds of MCTES

The transmission of music into the human uterus and the response to music of the human fetus and neonate

The aim of this study was to investigate whether music influences human life before birth. In order to determine the existence and character of music in the uterine acoustic environment, a study was conducted involving the insertion of a hydrophone through the cervix, next to the fetal head. The investigation was conducted on eight women in early labour. The average residual uterine sound of the eight subjects was measured at 65 dBA (A-weighted) re 20 µ.Pa in a 1 O KHz band, RMS averaged over 32-second records. Above this emerged the maternal voice, an external female voice and a male voice presented at approximately 65 dB (linear weighted). Pure tones between 50 Hz and 1 O KHz and orchestral music, all presented at 80 dB (linear weighted), were also shown to emerge above the residual uterine sound. Attenuation of external sound was observed to vary as a function of frequency, with less attenuation of lower frequencies. It was determined that the music was transmitted into the uterus without sufficient distortion to significantly alter the recognisable characteristics of the music. The fetal heart rate (FHA) response to a music stimulus (MS) and a vibroacoustic stimulus (VS) was measured in 40 subjects. Gestational age of the fetuses ranged from 32 to 42 weeks. The study included a control period with no acoustic stimulation; a period with the presentation of 5 music stimuli; and a period with the presentation of 5 vibroacoustic stimuli. A change in the FHA of 15 beats per minute or greater, lasting 15 seconds and occurring within 15 seconds of at least 2 of the 5 stimuli (or a tachycardia of greater than 15 beats per minute above the resting baseline, sustained for one minute or longer) was considered to be a positive response. The MS elicited a positive response in 35 of the fetuses (the 5 non-responses occurring in a period of low FHA variability) and all 40 fetuses responded to the VS (regardless of arousal state). In the third study, mothers attending childbirth education classes volunteered to listen to a prescribed music excerpt twice daily from the 34th week of pregnancy. Ten neonates (all clinically normal) were tested betw~en the 2nd and 5th day after birth. Investigators observed the effect of two music sti:Tiuli, the prescribed stimulus and a non-prescribed stimulus, on neonatal sucking of a non-nutritive nipple. A five-minute control period with no stimulation was compared with a ten-minute period during which two music stimuli were presented. By random allocation, either the prescribed music stimulus (PM) or the nonprescribed music (NM) was presented contingent upon sucking pressure. If a sucking burst was initiated, the PM stimulus was activated. On cessation of sucking, the NM stimulus was activated. Randomly, the procedure would be reversed for some of the subjects, where initiation of sucking activated the NM stimulus and cessation of sucking activated the PM stimulus. It was determined that the inter-burst intervals during the music period were significantly extended when coinciding with the PM stimulus and significantly shortened when coinciding with the NM stimulus.The studies indicated that music is transmitted into the uterus with insufficient distortion to alter the character of the music; that the normal fetus responds to a music stimulus from at least the 32nd week of gestation; and that the neonate alters the normal sucking pattern to activate longer periods of a music stimulus which has been repeatedly presented during the intrauterine stage and shorter periods of a novel music stimulus

Innovative Processing Algorithms for Fetal Magnetoencephalographic Data

Fetale Magnetenzepahalographie (fMEG) ermöglicht die Untersuchung der Entwicklung des zentralen und des autonomen Nervensystems bei Feten ab der 20. Schwangerschaftswoche. Wie normale Magnetenzephalographie bei Erwachsenen und Kindern ist auch fMEG eine nicht-invasive Methode und in der Anwendung vollkommen harmlos für Mutter und Kind. Die magnetischen Sensoren sind hierbei um das Abdomen der schwangeren Frau angeordnet. Die gute räumliche und zeitliche Auflösung erlaubt es, mütterliche und fetale Magnetokardiogramme gleichzeitig mit der fetalen Hirnaktivität zu messen. Die Signale der fetalen Magnetoenzephalographie werden vor allem zur Messung von auditiven und visuellen ereignisbezogenen Hirnreaktionen oder der spontanen Hirnaktivität verwendet. Wichtige Fragen zum Entwicklungsprozess des fetalen Gehirns und des autonomen Nervensystems sowie der mütterliche Einfluss auf den metabolischen und kognitiven Zustand des Neugeborenen können durch die Analyse der fetalen Magnetoenzephalographie-Signale geklärt werden. Die Auswertung der fetalen Hirnaktivität birgt einige Herausforderungen, da die Signale der fetalen und mütterlichen Herzaktivität etwa 10-1000 mal stärker sind als das fetale Hirnsignal. Daher ist es zwingend erforderlich, die Herzaktivität der Mutter und des Fetus zu erkennen und zu entfernen, bevor die fetale Hirnaktivität analysiert wird. Die derzeit verwendeten Methoden für die Erkennung und Entfernung der Herzaktivität funktionieren für die meisten Datensätze zuverlässig, die Verarbeitung enthält jedoch einige manuelle Schritte, was das Ganze sehr zeitaufwändig macht. Darüber hinaus ist die Signal Redistribution beim Entfernen der Herzaktivität ein bekanntes Problem, welches es schwierig macht, die Hirnaktivität später zu identifizieren. Das Ziel dieser Arbeit war es, die Auswertung der fMEG Daten schneller, besser und trotzdem leicht handhabbar zu machen. In dieser Arbeit werden zwei neue vollautomatisierte Methoden zur Erkennung und Entfernung der Herzaktivität vorgestellt. Der vollautomatisierte R-Peak Erkennungsalgorithmus (FLORA) verbessert die R-Peak Erkennung, indem er die Vorteile der zuvor verwendeten Methoden kombiniert und erweitert. Der Algorithmus zur vollautomatisierten Subtraktion der Herzaktivität (FAUNA) verbessert die Signalqualität und vereinfacht die Erkennung der Hirnaktivität, ohne Redistribution. Die Zuverlässigkeit der Daten wird dadurch erhöht, da keine manuelle Auswahl getroffen werden muss. Die Kombination beider Methoden in einem Programm zur vollautomatisierten Verarbeitung für die fetale Magnetoenzephalographie (FAIRY) macht die Datenauswertung nun einfach und schnell. Damit wird die fMEG Datenverarbeitung auf die "Big Data"- und "Automated Science"-Ära vorbereitet. Des Weiteren wurde eine Studie über die autonome und zentralnervöse Reaktion von Feten und Neugeborenen auf die mütterliche Stimme (AURORA) mit den neuen Datenverarbeitungsmethoden durchgeführt. Die Ergebnisse zeigten eine reduzierte Bewegung der Feten zwischen der 26. und 32. Schwangerschaftswoche und eine niedrigere Herzfrequenz während der ersten 20 Sekunden der Stimulation in den letzten Schwangerschaftswochen, als Reaktion auf die mütterliche Stimme. Zusätzlich fanden wir eine höhere Amplitude der Gehirnreaktion als Reaktion auf eine fremde Frauenstimme bei Neugeborenen.Fetal magnetoencephalography (fMEG) facilitates the investigation of both the nature and development of the fetal central and autonomic nervous system, starting at 20 weeks of gestational age. Like magnetoencephalography in children and adults, fetal magnetoencephalography is a noninvasive method and therefore completely harmless for both the mother and the child. Magnetic sensors in fMEG devices are arranged around the abdomen of the pregnant woman. The good spatial and temporal resolution allows to measure maternal and fetal magnetocardiograms simultaneously with fetal brain activity. The fMEG signals are mainly used to measure the auditory and visual event-related brain responses or the spontaneous brain activity. Important questions concerning the developmental process of the fetal brain, as well as the maternal influence on the metabolic and cognitive state of the newborn, can be clarified by the analysis of fMEG signals. The evaluation of the fetal brain activity poses some challenges, as the signals of fetal and maternal heart activity are 10-1000 times stronger than the fetal brain signal. Therefore, it is mandatory to detect and remove the heart activity of both the mother and the fetus before analyzing the fetal brain activity. The currently used methods for this detection and removal work well for most datasets, but the processing includes numerous manual steps and is therefore very time consuming. Furthermore, signal redistribution is a problem with the current methods, which makes later detection of the fetal brain activity challenging. The aim of this work was to make the evaluation of fMEG data faster, better and nevertheless, easy to use. In this thesis two new fully-automated procedures for the detection and removal of the heart activity are presented. The fully automated R-peak detection algorithm (FLORA) improves R-peak detection by combining and extending the advantages of the previously used methods. The algorithm for the fully automated subtraction of heart activity (FAUNA) improves the signal quality and facilitates detection of brain activity without the problem of redistribution. Furthermore these methods lead to a higher reliability of the data analysis since no manual interventions are necessary. Combining both methods in a tool for fully automated processing for fetal magnetoencephalography (FAIRY) makes data evaluation now easy and fast. This prepares the processing of fMEG data for the era of "Big Data" and "Automated Science". Additionally a study about the fetal and neonatal autonomous and central nervous response to maternal voice (AURORA) was performed using the new data processing methods. The results showed a reduced movement of fetuses between 26 and 32 weeks of pregnancy and a lower heart rate during the fist 20 seconds of stimulation in the last weeks of pregnancy as a reaction to maternal voice. We additionally found a higher amplitude of the brain response to voice onset of a stranger female voice in newborns

Mother's anxiety and depression during the third pregnancy trimester and neonate's mother versus stranger's face/voice visual preference

Background: Neonates show visual preference for their mother's face/voice and shift their attention from their mother to a stranger's face/voice after habituation. Aim: To assess neonate's mother versus stranger's face/voice visual preference, namely mother's anxiety and depression during the third pregnancy trimester and neonate's: 1) visual preference for the mother versus the stranger's face/voice (pretest visual preference), 2) habituation to the mother's face/voice and 3) visual preference for the stranger versus the mother's face/voice (posttest visual preference). Method: Mothers (N=100) filled out the Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI) both at the third pregnancy trimester and childbirth, and the “preference and habituation to the mother's face/voice versus stranger” paradigm was administered to their newborn 1 to 5 days after childbirth. Results: Neonates of anxious/depressed mothers during the third pregnancy trimester contrarily to neonates of non-anxious/non-depressed mothers did not look 1) longer at their mother's than at the stranger's face/voice at the pretest visual preference (showing no visual preference for the mother), nor 2) longer at the stranger's face/voice in the posttest than in the pretest visual preference (not improving their attention to the stranger's after habituation). Conclusion: Infants exposed to mother's anxiety/depression at the third gestational trimester exhibit less perceptual/social competencies at birth.Funded under the 2010 Science and Innovation Operational Program (POCI 2010) of the Community Support Board III, and supported by the European Community Fund FEDER. (POCI/SAU-ESP/ 56397/2004; Anxiety and depression in women and men during the transition to parenthood: Effects on fetal and neonatal behavior and development).We gratefully acknowledge the work of Filomena Louro of the Scientific Editing Programme of Universidade do Minho for revising this article

The conceptualization of a theoretical framework for a music intervention to improve auditory development in very preterm infants

Very preterm infants are at a high risk for language delays that can persist throughout their lifetime. The auditory system is rapidly developing and highly sensitive to acoustic stimulation during the third trimester of pregnancy. The acoustic nature of the womb provides the essential foundation for auditory perceptual skills necessary for language acquisition. In contrast, the NICU environment presents a wider spectrum of sounds that can alter the early development of the auditory system and cause delays in language acquisition. Research supports the importance of early exposure to speech sounds for optimal development of auditory perceptual ability and the critical role of the intrauterine characteristics of language. Pitches below 300 Hz, as well as rhythmic patterns and prosodic contours are highly salient intrauterine features of language that make up the infant’s initial auditory experience. The purpose of this study is to form a theoretical framework as a structure for understanding how intrauterine speech characteristics of pitch, rhythm, and prosody can be implemented as active ingredients in a music intervention to improve auditory development and long-term language outcomes in very premature infants. The framework is presented and described in detail. Implications for a future research agenda and applications for clinical practice are explored

The Intense World Syndrome – an Alternative Hypothesis for Autism

Autism is a devastating neurodevelopmental disorder with a polygenetic predisposition that seems to be triggered by multiple environmental factors during embryonic and/or early postnatal life. While significant advances have been made in identifying the neuronal structures and cells affected, a unifying theory that could explain the manifold autistic symptoms has still not emerged. Based on recent synaptic, cellular, molecular, microcircuit, and behavioral results obtained with the valproic acid (VPA) rat model of autism, we propose here a unifying hypothesis where the core pathology of the autistic brain is hyper-reactivity and hyper-plasticity of local neuronal circuits. Such excessive neuronal processing in circumscribed circuits is suggested to lead to hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms. In this view, the autistic spectrum are disorders of hyper-functionality, which turns debilitating, as opposed to disorders of hypo-functionality, as is often assumed. We discuss how excessive neuronal processing may render the world painfully intense when the neocortex is affected and even aversive when the amygdala is affected, leading to social and environmental withdrawal. Excessive neuronal learning is also hypothesized to rapidly lock down the individual into a small repertoire of secure behavioral routines that are obsessively repeated. We further discuss the key autistic neuropathologies and several of the main theories of autism and re-interpret them in the light of the hypothesized Intense World Syndrome