The Emergence of Human Consciousness: From Fetal to Neonatal Life

A simple definition of consciousness is sensory awareness of the body, the self, and the world. The fetus may be aware of the body, for example by perceiving pain. It reacts to touch, smell, and sound, and shows facial expressions responding to exter- nal stimuli. However, these reactions are probably preprogrammed and have a subcortical nonconscious origin. Furthermore, the fetus is almost continuously asleep and unconscious partially due to endog- enous sedation. Conversely, the newborn infant can be awake, exhibit sensory awareness, and process memorized mental representations. It is also able to differentiate between self and nonself touch, express emotions, and show signs of shared feelings. Yet, it is unreflective, present oriented, and makes little reference to concept of him/herself. Newborn infants display features characteristic of what may be referred to as basic consciousness and they still have to undergo considerable maturation to reach the level of adult consciousness. The preterm infant, ex utero, may open its eyes and establish minimal eye contact with its mother. It also shows avoidance reactions to harmful stimuli. However, the thalamocortical connections are not yet fully established, which is why it can only reach a minimal level of consciousness

Characterisation of the Haemodynamic Response Function (HRF) in the neonatal brain using functional MRI

Background: Preterm birth is associated with a marked increase in the risk of later neurodevelopmental impairment. With the incidence rising, novel tools are needed to provide an improved understanding of the underlying pathology and better prognostic information. Functional Magnetic Resonance Imaging (fMRI) with Blood Oxygen Level Dependent (BOLD) contrast has the potential to add greatly to the knowledge gained through traditional MRI techniques. However, it has been rarely used with neonatal subjects due to difficulties in application and inconsistent results. Central to this is uncertainity regarding the effects of early brain development on the Haemodynamic Response Function (HRF), knowledge of which is fundamental to fMRI methodology and analysis. Hypotheses: (1) Well localised and positive BOLD functional responses can be identified in the neonatal brain. (2) The morphology of the neonatal HRF differs significantly during early human development. (3) The application of an age-appropriate HRF will improve the identification of functional responses in neonatal fMRI studies. Methods: To test these hypotheses, a systematic fMRI study of neonatal subjects was carried out using a custom made somatosensory stimulus, and an adapted study design and analysis pipeline. The neonatal HRF was then characterised using an event related study design. The potential future application of the findings was then tested in a series of small experiments. Results: Well localised and positive BOLD functional responses were identified in neonatal subjects, with a maturational tendency towards an increasingly complex pattern of activation. A positive amplitude HRF was identified in neonatal subjects, with a maturational trend of a decreasing time-to-peak and increasing positive peak amplitude. Application of the empirical HRF significantly improved the precision of analysis in further fMRI studies. Conclusions: fMRI can be used to study functional activity in the neonatal brain, and may provide vital new information about both development and pathology

Task-based fMRI investigation of the newborn brain: sensorimotor development and learning

Human brain development relies upon the interaction between genetic and environmental factors, and the latter plays a critical role during the perinatal period. In this period, neuronal plasticity through experience-dependent activity is enhanced in the sensory systems, and drive the maturation of the brain. While plasticity is essential for maturation, it is also a source of vulnerability as altered early experiences may interact with the normal course of development. This is particularly evident in infants born preterm, who are prematurely exposed to a sensory-rich environment, and at risk or neurodevelopmental disorders. In keeping with the somatosensory system being at a critical period for development during late gestation, sensorimotor disorders, such as cerebral palsy, are more common in preterm compared with full-term born infants. It is therefore important to understand the normal trajectory of sensorimotor development and how this may be moulded by early sensory experiences. It is well acknowledged that the sensorimotor cortex is topographically organised so that different body parts map to a specific location within the cortex and this map is generally referred to as the ``homunculus". Although the somatotopy has been well characterised in the mature brain, it remains unknown when this organisation emerges during development. Animal studies hints that functional cortical maps might emerge across the equivalent period to the third trimester of human gestation, nevertheless there is currently no evidence. Therefore, I first investigated the topography of the preterm somatosensory cortex in a group of newborn infants. In this purpose I used fMRI and automated robotic tools and measured the functional responses to different sensory simulations (delivered to the mouth, wrists and ankles). The results provide evidence that it is possible to identify distinct areas in the somatosensory cortex devoted to different body parts even in the preterm brain supporting the presence of an immature \textit{homunculus}. Next, I wanted to investigate how activity and development in the sensorimotor system are influenced by experience. Experience-dependent plasticity is the basis of learning (e.g. adaptive behaviour), which is observed in newborn infants. Associative learning in particular has been widely investigated in infants, however, the underlining neuronal processes have previously been poorly understood. To study the neural correlates of associative learning in newborn infants, I developed and used a classical conditioning paradigm in combination with robot-assisted fMRI. The results confirm that associative learning can occur even at this early stage of life and with non-aversive stimuli. More importantly, I could observe learning-induced changes in brain activity within the primary sensory cortices, suggesting that such experience can shape cortical circuitry and is likely to influence early brain development.Open Acces

Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain

Dall’Orso S, Steinweg J, Allievi AG, Edwards AD, Burdet E, Arichi T. Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain. Cerebral Cortex. 2018;28(7):2507-2515

Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.Lääketieteellisen teknologian kehitys on vasta viime vuosina mahdollistanut lasten aivotoiminnan tarkan, objektiivisen tutkimuksen. Näin ollen esimerkiksi aistiärsykkeiden aivoprosessoinnista vastasyntyneillä tiedetään varsin vähän, samoin kuin monien aivotoimintojen kehittymisestä lapsen kasvaessa. Myös ymmärrys erilaisten aivovaurioiden vaikutuksesta kehittyviin aivoihin on puutteellista. Magnetoenkefalografialla (MEG) tutkitaan aivohermosolujen toimintaa mittaamalla niissä syntyvien sähkövirtojen tuottamia magneettikenttiä pään ulkopuolelta. Väitöskirjassa MEG:n avulla tutkittiin tuntoaivokuoren toimintaa vastasyntyneillä ja tämän toiminnan kehitystä ensimmäisten elinvuosien aikana. Lisäksi tuntoaivokuoren toimintaa tarkasteltiin pikkukeskosena syntyneillä vauvoilla sekä nuorilla, joilla on varhaisen aivovaurion aiheuttama toispuoleinen CP-vamma. Jo vastasyntyneellä useat aivoalueet aktivoituivat käden alueen kosketusärsykkeen jälkeen. Tuntoaivokuoren aktiivisuus poikkesi kuitenkin oleellisesti aikuisesta: tietyt aikuistyyppiset aivovasteet puuttuivat vastasyntyneiltä täysin heijastaen vastasyntyneen vauvan hermoston keskeneräistä kehitysvaihetta. Tuntoaivovasteet kehittyivät iän myötä järjestelmällisesti siten, että kaksivuotiailla ne alkoivat morfologisesti muistuttaa aikuisten vasteita. Pikkukeskosten primaarisen tuntoaivokuoren vaste oli lasketussa ajassa heikompi kuin terveillä täysaikaisilla vauvoilla, mikä voi johtua pienemmästä aktivoituneesta hermosolujoukosta tai aktivaation epäsynkroniasta. Sekundaarisen tuntoaivokuoren vasteen puuttuminen liittyi poikkeaviin ultraääni- ja magneettikuvauslöydöksiin. Tämän havainnon ennusteellista merkitystä selvitetään parhaillaan seurantatutkimuksella. CP-vammaisilla nuorilla tuntoaivovasteissa havaittiin verrokkeihin nähden useita poikkeavuuksia, jotka olivat osin laaja-alaisempia kuin oli pääteltävissä kliinisistä oireista tai aivojen rakenteellisesta vauriosta. Esimerkiksi potilailla, joiden sairauden taustalla oli subkortikaalinen aivovaurio, etu- ja pikkusormien edustusalueet tuntoaivokuorella olivat verrokkeihin nähden lähempänä toisiaan sekä vaurion puoleisessa että vastakkaisessa aivopuoliskossa. Aivojen erilaisten rakenteellisten vaurioiden aiheuttamien toiminnallisten muutosten tarkempi ymmärtäminen voi osoittautua merkittäväksi CP-potilaiden kuntoutuksen ja hoidon yksilöllisessä räätälöinnissä

Association between hemodynamic activity and motor performance in six-month-old full-term and preterm infants: a functional near-infrared spectroscopy study

FAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThis study aimed to assess task-induced activation in motor cortex and its association with motor performance in full-term and preterm born infants at six months old. A cross-sectional study of 73 sixmonth- old infants was conducted (35 full-term and 38 preterm infants). Motor performance was assessed using the Bayley Scales of Infant Development third edition-Bayley-III. Brain hemodynamic activity during motor task was measured by functional near-infrared spectroscopy (fNIRS). Motor performance was similar in full-term and preterm infants. However, differences in hemodynamic response were identified. Full terms showed a more homogeneous unilateral and contralateral activated area, whereas in preterm-born the activation response was predominantly bilateral. The full-term group also exhibited a shorter latency for the hemodynamic response than the preterm group. Hemodynamic activity in the left sensorimotor region was positively associated with motor performance measured by Bayley-III. The results highlight the adequacy of fNIRS to assess differences in task-induced activation in sensorimotor cortex between groups. The association between motor performance and the hemodynamic activity require further investigation and suggest that fNIRS can become a suitable auxiliary tool to investigate aspects of neural basis on early development of motor abilities.5118FAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO215502012/02500-82013/07559-

The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity

The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder which occur frequently in preterm children. Overall, we find a robust, modular, symmetrical functional brain organisation at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher-order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity

Secondary somatosensory cortex evoked responses and 6-year neurodevelopmental outcome in extremely preterm children

Objective: We assessed in extremely preterm born (EPB) children whether secondary somatosensory cor-tex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6 years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children. Methods: 39 EPB children underwent MEG with tactile stimulation at TEA. At age 6 years, 32 EPB and 26 TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6 years. Results: Unilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p = 0.03). At age 6 years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p = 0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p = 0.02). Conclusions: Unilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children. Significance: Neurophysiological methods may provide new means for outcome prognostication in EPB children. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe