Sleep as a window for evaluating neurodevelopmental outcome: which impact on the brain of preterm infants? A prospective study on prematurity from a biological neuropsychiatry perspective

Background. Newborns and infants spend most of their time sleeping an immature sleep, which allows brain maturation a good neurodevelopment. Preterm birth is associated with abnormal brain development and alterations in later-in-life sleep patterns, carrying a high social burden, even when not accompanied by major neurological damages. Which impact prematurity itself can have on early sleep architecture, which influence it can have on well- known adverse outcomes, and which role brain lesions play in determining sleep patterns in preterm infants are still matter of debate. This exploratory pilot study aimed to describe the distribution of sleep states among very low birth weight (VLBW) infants, and to correlate it with neurobehavioral assessment at 35 weeks of post-menstrual age (PMA), and to observe if these persisted at term equivalent age (TEA) and at 6 months of corrected age (CA). Secondly, it aimed to assess if the presence of a major or minor brain lesion detected at MRI can affect sleep duration, distribution and quality. Methods. 10 VLBW were assessed at 34±2 weeks PMA with a 24-hours video- polysomnographic recording and received a neurobehavioral examination at the moment of the recording and at TEA (with Neonatal Behavior Assessment Scale; Hammersmith Neurological Neonatal Examination, and the neonatal visual battery). They were followed- up at 6 months CA with Griffiths’ Mental Development Scale III edition. Analysis of sleep stages distribution and spectra was conducted. Results. Total sleep time and total amount of transitional sleep (TS) significantly positively correlated with neurological, and neurobehavioral assessment at 34 weeks PMA, at TEA and with neurodevelopment at 6 months CA, while Sleep Onset Active Sleep (SOAS) had a negative association. Infants carrying severe-moderate brain lesions showed lower Total Sleep time (66.9% ± 7.39 vs 72.2% ± 3.52, p = 0.047) accompanied by a higher prevalence of SOAS (23.9% ± 10.2 vs 12.26% ± 5.5 p = 0.048), and showed a gradient for higher power of posterior slow activity (slow δ and δ) during SOAS from the posterior cerebral regions. Conclusions. Understanding sleep mechanism among preterm infants might provide future therapeutic/management strategies, which need to encompass sleep care. Further analyses with larger samples and more complex methods are claimed

Effects of SIDS risk factors and hypoxia on cardiovascular control in infants

Background and aims. Sudden infant death syndrome (SIDS) is a rare lethal event occurring in 0.1 to 0.3 of infants. In Finland, 10 to 20 infants die from SIDS annually. Research has defined many risk factors for SIDS, but the cascade leading to death remains unexplained. Cardiovascular recordings of infants succumbing to SIDS, as well as animal models, suggest that the final sequelae involve cardiovascular collapse resembling hypotensive shock. There is also evidence of previous hypoxia in SIDS infants. In animal studies, vestibulo-mediated cardiovascular control has been shown to be important in hypotensive shock. Hence, we hypothetized that SIDS victims may have impaired vestibulo-mediated cardiovascular control, possibly due to previous hypoxic episodes. In this thesis, we studied cardiovascular control, and especially vestibulo-mediated cardiovascular control in infants with known risk factors for SIDS at 2 to 4 months of age when the risk for SIDS is highest. Study subjects. A full polysomnographic recording with continuous blood pressure (BP) measurement was performed in 50 infants at 2-4 months of age: 20 control infants, nine infants with univentricular heart (UVH) suffering from chronic hypoxia, 10 infants with bronchopulmonary dysplasia (BPD) with intermittent postnatal hypoxic events, and 11 infants whose mothers had smoked during pregnancy, and thus had been exposed to intrauterine hypoxia and nicotine, were studied. In addition, 20 preterm infants were studied at the gestational age of 34-39 weeks to evaluate developmental aspects of cardiovascular control during head-up tilt test and vestibular stimulus. Methods. Linear side motion and 45° head-up tilt tests were performed in quiet non-rapid eye movement sleep (NREM). Heart rate (HR) and BP responses were analysed from the tests without signs of subcortical or cortical arousal. In addition, HR variability during NREM sleep was assessed. As a general marker of cardiovascular reactivity, HR response to spontaneous arousal from NREM sleep was also evaluated. Results.Side motion test. In the side motion test, control infants presented a biphasic response. First, there was a transient increase in HR and BP. This was followed by a decrease in BP to below baseline, and a return to baseline in HR. All other infant groups showed altered responses. UVH infants and preterm infants near term age had markedly reduced responses. Infants with BPD presented with variable responses: some responded similarly to controls, whereas others showed no initial increase in BP, and the following BP decrease was more prominent. Infants with intrauterine exposure to cigarette smoke showed flat initial BP responses, and the following decrease was more prominent, similarly to a subgroup of BPD infants. Tilt test. Control infants presented with a large variability in BP responses to head-up tilting. On average, systolic BP remained, at first, close to baseline, and diastolic BP increased, after which both decreased and remained below baseline even at the end of the tilt test. On average, HR showed a biphasic response with an initial increase followed by a decrease to below and, finally, a return to baseline. UVH infants showed a similar BP response, but their HR response was tachycardic. Preterm infants with BPD presented with an even greater variability in their BP responses to head-up tilts than control infants, but the overall response as a group did not differ from that of the controls. The tilt response of infants exposed to maternal cigarette smoking during pregnancy did not markedly differ from the control response. Preterm infants near term age showed attenuated responses in both cardiovascular measures, together with greater inter-subject variability compared to the control infants. Discussion. In conclusion, the studied infants with SIDS risk factors showed altered vestibulo-mediated cardiovascular control during the linear side motion test and head-up tilt test. The findings support our initial hypothesis that some infants with SIDS risk factors have defective vestibulo-mediated cardiovascular control, which may lead to death in life-threatening situations.Kätkytkuolemat ovat harvinaisia, mutta ne ovat edelleen suurin yksittäinen syy täysiaikaisena syntyneiden imeväisten kuolemaan. Suomessa kätkytkuolemaan menehtyy vuosittain 10-20 lasta. Kätkytkuoleman syytä ei tiedetä. Epidemiologisten tutkimusten avulla kätkytkuoleman riskitekijät tunnetaan hyvin; näitä ovat mm. vatsallaan nukkuminen, äidin raskaudenaikainen tupakointi ja keskosuus. Selällään nukuttamisen yleistymisen myötä kätkytkuolemien määrä on vähentynyt olennaisesti. Koe-eläintöissä ja muutamassa kätkytkuoleman aikaisessa seurantanauhoituksessa on viitteitä siitä, että kätkytkuoleman mekanismi todennäköisesti muistuttaa verenvuotosokin loppuvaiheen kaltaista verenkiertoelimistön toiminnan romahtamista. Koe-eläintöiden perusteella tällaisessa sokkitilanteessa tasapainotumakevälitteinen verenkierron säätely on tärkeää. Tämän tutkimuskokonaisuuden pääolettaman mukaan kätkytkuolleilla on puutteellinen tasapainotumakevälitteinen sykkeen ja verenpaineen säätely. Koska kätkytkuolleilla on myös todettu merkkejä hapenpuutteesta ennen kuolemaa, voi poikkeavan tasapainotumakevälitteisen verenkierron säätelyn syynä olla edeltänyt hapenpuute: riskiryhmistä esimerkiksi keskosilla lyhytkestoiset hapenpuutejaksot ja äidin raskaudenaikaiselle tupakoinnille altistuneilla lapsilla pitkäaikainen lievä hapenpuute sikiöaikana. Myös pitkäaikaisesta syntymän jälkeisestä hapenpuutteesta kärsivillä yksikammiosydämisillä imeväisillä on todettu äkillisiä, kätkytkuoleman kaltaisia kuolemia. Tutkimme imeväisen verenkierron säätelyä unen aikana rekisteröimällä verenkiertovasteita sivuttaissiirto- ja kippilavatestille täysiaikaisilla imeväisillä sekä imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä tai hapenpuutetta. Unirekisteröinti tehtiin yhteensä 70 imeväiselle. 2-4 kuukauden korjatussa iässä tutkittiin 20 täysiaikaista verrokkia, 10 bronkopulmonaalisesta dysplasiasta kärsivää keskosta, 9 yksikammiosydämistä imeväistä sekä 11 imeväistä, joiden äidit tupakoivat raskauden aikana. Lisäksi tutkimme 20 keskosta 34-39 raskausviikon iässä sykkeen ja verenpaineen säätelyn kehityksen kartoittamiseksi. Sivuttaissiirtotesti sekä 45° kippilavatesti pää ylöspäin tehtiin rauhallisessa ei-REM-unessa. Terveiden täysiaikaisten verrokkien verenpaine- ja sykevasteita käytettiin vertailukohtana muiden ryhmien vasteita arvioitaessa. Syke- ja verenpainevasteet arvioitiin testeistä, joissa ei ollut viitettä havahtumisesta tai heräämisestä. Sydämen sykkeen vaihtelevuutta ja spontaanin heräämisen aiheuttamaa sykevastetta käytettiin kuvaamaan yleistä verenkiertoelimistön säätelyn herkkyyttä. Sivuttaissiirtotestissä verrokit reagoivat kaksivaiheisella syke- ja verenpainevasteella. Sekä verenpaine että syke nousivat aluksi, jonka jälkeen verenpaine laski alle lähtötason ennen paluuta lähtötasoon, ja syke palasi lähtötasoon. Muissa tutkituissa ryhmissä vasteet poikkesivat normaalivasteista. Yksikammiosydänlapsilla sekä lähellä laskettua aikaa tutkituilla keskosilla syke- ja verenpainevasteet sivuttaissiirrolle olivat hyvin vaimeat. Puolet bronkopulmonaalisesta dysplasiasta kärsivistä imeväisistä reagoi samoin kuin verrokit, mutta puolella verenpaineen nousu puuttui ja sitä seurannut verenpaineen lasku oli selvästi normaalia syvempi. Myös imeväisillä, joiden äidit olivat tupakoineet raskauden aikana, verenpaineen alkunousu puuttui ja sitä seurannut verenpaineen lasku oli verrokkeja syvempi. Kippilavatestissä täysiaikaisten verrokkien verenpainevasteet olivat hyvin vaihtelevat. Keskimäärin testin alussa systolinen verenpaine pysyi ennallaan ja diastolinen nousi. Testin jatkuessa molemmat laskivat alle lähtötason, jossa ne pysyivät vielä testin lopettamisen jälkeenkin. Verrokkien sykevasteet olivat selkeästi yhtenevämmät ja vaste oli kaksivaiheinen: alun sykkeen nousua seurasi sykkeen lasku alle lähtötason ja paluu takaisin lähtötasoon. Yksikammiosydänlasten verenpainevasteet olivat verrokkien kaltaiset, mutta heidän sykkeensä pysyi korkeana koko testin ajan. Bronkopulmonaalisesta dysplasiasta kärsivien imeväisten verenpainevasteissa oli vielä voimakkaampaa vaihtelua kuin verrokkien vasteissa, mutta ryhmänä heidän vasteensa ei eronnut verrokeista. Raskaudenaikaiselle tupakoinnille altistuneiden imeväisten verenkiertovasteet eivät eronneet verrokeista. Lähellä laskettua aikaa tutkittujen keskosten syke- ja verenpainevasteissa oli suurta vaihtelua verrattuna täysiaikaisiin verrokkeihin, mutta ryhmänä verenkiertovasteet olivat vaimeammat kuin verrokeilla. Tässä tutkimuksessa todettiin poikkeava tasapainotumakevälitteinen verenkierron säätely imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä ja edeltäneitä hapenpuutejaksoja. Tutkimustulokset tukevat etukäteisolettamustamme, että heikentynyt tasapainotumakevälitteinen verenkierron säätely imeväisillä voi olla osaltaan johtamassa kätkytkuolemaan henkeä uhkaavassa tilanteessa

Mental sleep activity and disturbing dreams in the lifespan

Sleep significantly changes across the lifespan, and several studies underline its crucial role in cognitive functioning. Similarly, mental activity during sleep tends to covary with age. This review aims to analyze the characteristics of dreaming and disturbing dreams at dierent age brackets. On the one hand, dreams may be considered an expression of brain maturation and cognitive development, showing relations with memory and visuo-spatial abilities. Some investigations reveal that specific electrophysiological patterns, such as frontal theta oscillations, underlie dreams during sleep, as well as episodic memories in the waking state, both in young and older adults. On the other hand, considering the role of dreaming in emotional processing and regulation, the available literature suggests that mental sleep activity could have a beneficial role when stressful events occur at dierent age ranges. We highlight that nightmares and bad dreams might represent an attempt to cope the adverse events, and the degrees of cognitive-brain maturation could impact on these mechanisms across the lifespan. Future investigations are necessary to clarify these relations. Clinical protocols could be designed to improve cognitive functioning and emotional regulation by modifying the dream contents or the ability to recall/non-recall them

14 challenges for conducting social neuroscience and longitudinal EEG research with infants

The use of electroencephalography (EEG) to study infant brain development is a growing trend. In addition to classical longitudinal designs that study the development of the neural, cognitive and behavioural function, new areas of EEG application are emerging, such as novel social neuroscience paradigms using dual infant-adult EEG recordings. However, most of the experimental designs, analysis methods, as well as EEG hardware were originally developed for single-person adult research. When applied to the study of infant development, adult-based solutions often pose unique problems that may go unrecognised. Here, we identify 14 challenges that infant EEG researchers may encounter when designing new experiments, collecting data, and conducting data analysis. Challenges related to the experimental design are: (1) small sample size and data attrition, and (2) varying arousal in younger infants. Challenges related to data acquisition are: (3) determining the optimal location for reference and ground electrodes, (4) control of impedance when testing with the high-density sponge electrode nets, (5) poor fit of standard EEG caps to the varying infant head shapes, and (6) ensuring a high degree of temporal synchronisation between amplifiers and recording devices during dual-EEG acquisition. Challenges related to the analysis of longitudinal and social neuroscience datasets are: (7) developmental changes in head anatomy, (8) prevalence and diversity of infant myogenic artefacts, (9) a lack of stereotypical topography of eye movements needed for the ICA-based data cleaning, (10) and relatively high inter-individual variability of EEG responses in younger cohorts. Additional challenges for the analysis of dual EEG data are: (11) developmental shifts in canonical EEG rhythms and difficulties in differentiating true inter-personal synchrony from spurious synchrony due to (12) common intrinsic properties of the signal and (13) shared external perturbation. Finally, (14) there is a lack of test-retest reliability studies of infant EEG. We describe each of these challenges and suggest possible solutions. While we focus specifically on the social neuroscience and longitudinal research, many of the issues we raise are relevant for all fields of infant EEG research

14 challenges and their solutions for conducting social neuroscience and longitudinal EEG research with infants.

The use of electroencephalography (EEG) to study infant brain development is a growing trend. In addition to classical longitudinal designs that study the development of neural, cognitive and behavioural functions, new areas of EEG application are emerging, such as novel social neuroscience paradigms using dual infant-adult EEG recordings. However, most of the experimental designs, analysis methods, as well as EEG hardware were originally developed for single-person adult research. When applied to study infant development, adult-based solutions often pose unique problems that may go unrecognised. Here, we identify 14 challenges that infant EEG researchers may encounter when designing new experiments, collecting data, and conducting data analysis. Challenges related to the experimental design are: (1) small sample size and data attrition, and (2) varying arousal in younger infants. Challenges related to data acquisition are: (3) determining the optimal location for reference and ground electrodes, (4) control of impedance when testing with the high-density sponge electrode nets, (5) poor fit of standard EEG caps to the varying infant head shapes, and (6) ensuring a high degree of temporal synchronisation between amplifiers and recording devices during dual-EEG acquisition. Challenges related to the analysis of longitudinal and social neuroscience datasets are: (7) developmental changes in head anatomy, (8) prevalence and diversity of infant myogenic artefacts, (9) a lack of stereotypical topography of eye movements needed for the ICA-based data cleaning, (10) and relatively high inter-individual variability of EEG responses in younger cohorts. Additional challenges for the analysis of dual EEG data are: (11) developmental shifts in canonical EEG rhythms and difficulties in differentiating true inter-personal synchrony from spurious synchrony due to (12) common intrinsic properties of the signal and (13) shared external perturbation. Finally, (14) there is a lack of test-retest reliability studies of infant EEG. We describe each of these challenges and suggest possible solutions. While we focus specifically on the social neuroscience and longitudinal research, many of the issues we raise are relevant for all fields of infant EEG research.This research was funded by an ESRC Transforming Social Sciences collaboration grant (ES/N006461/1) to VL and SW, and by ESRC FRL Fellowship (ES/N017560/1) to SW

Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control

Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology

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

Applications of aerospace technology in the public sector

Current activities of the program to accelerate specific applications of space related technology in major public sector problem areas are summarized for the period 1 June 1971 through 30 November 1971. An overview of NASA technology, technology applications, and supporting activities are presented. Specific technology applications in biomedicine are reported including cancer detection, treatment and research; cardiovascular diseases, diagnosis, and treatment; medical instrumentation; kidney function disorders, treatment, and research; and rehabilitation medicine