Bernard Dan

Vrije Universiteit Brussel, Bruxelles, Brussels Capital, Belgium

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Publications (251)615.94 Total impact

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    ABSTRACT: Nature Reviews Disease Primers article number: 15082; doi:10.1038/nrdp.2015.82; published online 7 Jan 2016 In the version of the article originally published, two of the reference highlights were included in the incorrect place.
    Preview · Article · Jan 2016
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    ABSTRACT: In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto-central delta and contralateral central mu to parietal theta presented here.
    Full-text · Article · Dec 2015 · Frontiers in Psychology
  • Bernard Dan

    No preview · Article · Nov 2015 · Developmental Medicine & Child Neurology
  • Bernard Dan · Guy Cheron

    No preview · Article · Jul 2015 · Journal of pediatric neurology: JPN
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    ABSTRACT: Preventable risk factors for sudden infant death syndrome include the infant's environment and response characteristics. Various infant and environmental factors thus modify the vital cardiocirculatory, respiratory and arousal controls in healthy infants. Similar changes in cardiorespiratory and autoresuscitative responses have been found in the analysis of sleep recordings of victims of sudden infant death syndrome. It is not known why some infants die, while others show similar changes but survive in the first year of life. The death could be due to the degree of the initial immature controls, to the severity of the additional challenge, or to a combined effect of inadequate autoresuscitative mechanisms and the cumulative influence of infant and/or environmental stressors.
    No preview · Article · Jul 2015 · Journal of pediatric neurology: JPN
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    ABSTRACT: Gait is an essential human activity which organizes many functional and cognitive behaviors. The biomechanical constraints of bipedalism implicating a permanent control of balance during gait are taken into account by a complex dialogue between the cortical, subcortical and spinal networks. This networking is largely based on oscillatory coding, including changes in spectral power and phase-locking of ongoing neural activity in theta, alpha, beta and gamma frequency bands. This coding is specifically modulated in actual gait execution and representation, as well as in contexts of gait observation or imagination. A main challenge in integrative neuroscience oscillatory activity analysis is to disentangle the brain oscillations devoted to gait control. In addition to neuroimaging approaches, which have highlighted the structural components of an extended network, dynamic high-density EEG gives non-invasive access to functioning of this network. Here we revisit the neurophysiological foundations of behavior-related EEG in the light of current neuropsychological theoretic frameworks. We review different EEG rhythms emerging in the most informative paradigms relating to human gait and implications for rehabilitation strategies. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Neuropsychologia
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    ABSTRACT: Background: Children born preterm are at risk for developmental cerebral visual impairment. Several modalities of visual evoked potentials recording have been used to approach prognosis. The recent development of high-density EEG protocols allows evaluation of the oscillatory content of cortical activities evoked by specific stimulation. We aimed to document maturational EEG changes in response to visual stimulation in infants born preterm. Aim: to document maturational EEG changes in response to visual stimulation in infants born preterm. Material and methods: 12 newborn infants (8 boys/4 girls) born preterm (28-31 weeks of gestation) were recorded at term age and 3 months later using the ActiveTwo system (Biosemi) high-density EEG. Exclusion criteria were craniofacial congenital malformations, known genetic syndrome. No infants had retinopathy, intraventricular hemorrhage or cystic periventricular leukomalacia. We used size-adapted head caps with 64 sintered active Ag/AgCl electrodes positioned according to the 10/20 system. Sampling rate was 2048 Hz. We performed EEGLab analysis of theta, alpha, beta and gamma frequency spatiotemporal contents (incl. event-related spectral perturbation and intertrial coherence) of event related potentials evoked by slow (1Hz) and fast (9Hz) visual flash stimulation. Summed ear lobe potentials were used as reference. We used 1 Hz high-pass filter, 60 Hz low-pass filter and 48-52 Hz notch filter. Results: We recorded consistent changes posteriorly at the expected latency of visual evoked potentials for age (around 200ms following 1Hz stimulation) including increased alpha-beta power as well as local synchrony maximal in the same range of oscillations bands. At higher rates, resonance resulted in further power increase within the stimulation frequency with superimposed oscillatory processes in the beta and gamma range. The changes were significantly different at 3 months corrected age compared to term age. Conclusion: Oscillatory study of high-density EEG in infants allows precise maturational documentation of visual responses in young infants, paving the way for increased understanding of central processes involved during early neurological development. It may contribute to documenting physiological and deviant neurophysiological organization in the wider context of early neurodevelopmental diagnosis.
    Full-text · Conference Paper · May 2015
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    ABSTRACT: Background: Angelman syndrome is a genetic neurodevelopmental disorder recognised to show characteristic (non-epileptic) high-amplitude slow rhythmic electroencephalographic patterns. These hypersynchronous neuronal activities have been studied to approach the pathophysiology of the condition. Aim: to analyse these patterns with enhanced recording technique (high-density EEG) and analysis method, using a recently developed technique for identifying subtle short-term repeated patterns that may be masked by non-stationarities, noise, and artefacts. Material and methods: 4 children (aged 2 to 5) with Angelman syndrome due to 15q11-q13 deletion. High-density EEG were recorded at resting state using the ActiveTwo system (Biosemi) with size-adapted head caps with 128 sintered active Ag/AgCl electrodes positioned radially equidistant from CZ. Sampling rate was 2048 Hz. We performed a channel spectra for the 128 channel of a 5 minutes resting state recording in order to find regions of interest for slow frequency bands. We performed a wave trigger averaging over the peaks of activity of this region and averaged it on a period of 2 seconds (-1,1second) centered on the peak activity. To localise the generator of this activity, we performed an inverse solution analysis with Sloreta matrix. Results: we found high-amplitude (from 140 μV to 188 μV) slow frequency oscillation (4Hz in all patients) mostly in parieto-occipital regions. The generator of this activity was located in the parietal lobe, in Brodman areas 7. Discussion: The slow rhythmic activity is consistent with a model of cortical and thalamo-cortical dysfunction resulting from dysregulation of synaptic GABAergic neurotransmission due to lack of UBE3A expression, or other factors. Brodmann area 7 specifically identified here correspond to the somatosensory association cortex, which play key roles in visuo-motor coordination and in language processing, both of which show specific impairments in Angelman syndrome.
    Full-text · Conference Paper · May 2015
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    ABSTRACT: Paracetamol (acetaminophen) remains the first line for the treatment of pain and fever in pregnancy. Recently published epidemiological studies suggested a possible association between paracetamol exposure in utero and attention-deficit-hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development issues in children. However, the effects observed are in the weak to moderate range, and limitations in the studies' design prevent inference on a causal association with ADHD/HKD or child neurological development. In parallel, recent animal data showed that cognition and behaviour may be altered following exposure to therapeutic doses of paracetamol during early development. These effects may be mediated by interference of paracetamol with brain-derived neurotrophic factor, neurotransmitter systems (including serotonergic, dopaminergic, adrenergic, as well as the endogenous endocannabinoid systems), or cyclooxygenase-2. However, no firm conclusion can be made on the relevance of these observations to humans. We conclude that additional well-designed cohort studies are necessary to confirm or disprove the association. In the context of current knowledge, paracetamol is still to be considered safe in pregnancy and should remain the first-line treatment for pain and fever. © 2015 Mac Keith Press.
    No preview · Article · Apr 2015 · Developmental Medicine & Child Neurology
  • Bernard Dan · Karine Pelc · Ana M Cebolla · Guy Cheron
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    ABSTRACT: Efforts to document early changes in the developing brain have resulted in the construction of increasingly accurate structural images based on magnetic resonance imaging (MRI) in newborn infants. Tractography diagrams obtained through diffusion tensor imaging have focused on white matter microstructure, with particular emphasis on neuronal connectivity at the level of fibre tract systems. Electroencephalography (EEG) provides a complementary approach with more direct access to brain electrical activity. Its temporal resolution is excellent, and its spatial resolution can be enhanced to physiologically relevant levels, through the combination of high-density recordings (e.g. by using 64 channels in newborn infants) and mathematical models (e.g. inverse modelling computation), to identify generators of different oscillation bands and synchrony patterns. The integration of functional and structural topography of the neonatal brain provides insights into typical brain organization, and the deviations seen in particular contexts, for example the effect of hypoxic-ischaemic insult in terms of damage, eventual reorganization, and functional changes. Endophenotypes can then be used for pathophysiolgical reasoning, management planning, and outcome measurements, and allow a longitudinal approach to individual developmental trajectories. © The Authors. Journal compilation © 2015 Mac Keith Press.
    No preview · Article · Apr 2015 · Developmental Medicine & Child Neurology
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    ABSTRACT: Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception-action-cognition-environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed. © 2015 The Authors. Developmental Medicine & Child Neurology © 2015 Mac Keith Press.
    Full-text · Article · Apr 2015 · Developmental Medicine & Child Neurology
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    ABSTRACT: The highly stereotyped, crystal-like architecture of the cerebellum has long served as a basis for hypotheses with regard to the function(s) that it subserves. Historically, most clinical observations and experimental work have focused on the involvement of the cerebellum in motor control, with particular emphasis on coordination and learning. Two main models have been suggested to account for cerebellar functioning. According to Llinás's theory, the cerebellum acts as a control machine that uses the rhythmic activity of the inferior olive to synchronize Purkinje cell populations for fine-tuning of coordination. In contrast, the Ito-Marr-Albus theory views the cerebellum as a motor learning machine that heuristically refines synaptic weights of the Purkinje cell based on error signals coming from the inferior olive. Here, we review the role of timing of neuronal events, oscillatory behavior, and synaptic and non-synaptic influences in functional plasticity that can be recorded in awake animals in various physiological and pathological models in a perspective that also includes non-motor aspects of cerebellar function. We discuss organizational levels from genes through intracellular signaling, synaptic network to system and behavior, as well as processes from signal production and processing to memory, delegation, and actual learning. We suggest an integrative concept for control and learning based on articulated oscillation templates.
    Full-text · Article · Mar 2015 · The Cerebellum
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    ABSTRACT: Angelman syndrome (AS) is a genetic neurodevelopmental disorder in which cerebellar functioning impairment has been documented despite the absence of gross structural abnormalities. Characteristically, a spontaneous 160 Hz oscillation emerges in the Purkinje cells network of the Ube3a (m-/p+) Angelman mouse model. This abnormal oscillation is induced by enhanced Purkinje cell rhythmicity and hypersynchrony along the parallel fiber beam. We present a pathophysiological hypothesis for the neurophysiology underlying major aspects of the clinical phenotype of AS, including cognitive, language and motor deficits, involving long-range connection between the cerebellar and the cortical networks. This hypothesis states that the alteration of the cerebellar rhythmic activity impinges cerebellar long-term depression (LTD) plasticity, which in turn alters the LTD plasticity in the cerebral cortex. This hypothesis was based on preliminary experiments using electrical stimulation of the whiskers pad performed in alert mice showing that after a 8 Hz LTD-inducing protocol, the cerebellar LTD accompanied by a delayed response in the wild type (WT) mice is missing in Ube3a (m-/p+) mice and that the LTD induced in the barrel cortex following the same peripheral stimulation in wild mice is reversed into a LTP in the Ube3a (m-/p+) mice. The control exerted by the cerebellum on the excitation vs. inhibition balance in the cerebral cortex and possible role played by the timing plasticity of the Purkinje cell LTD on the spike-timing dependent plasticity (STDP) of the pyramidal neurons are discussed in the context of the present hypothesis.
    Full-text · Article · Nov 2014 · Frontiers in Systems Neuroscience
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    ABSTRACT: Biological motion observation has been recognized to produce dynamic change in sensorimotor activation according to the observed kinematics. Physical plausibility of the spatial-kinematic relationship of human movement may play a major role in the top-down processing of human motion recognition. Here, we investigated the time course of scalp activation during observation of human gait in order to extract and use it on future integrated brain-computer interface using virtual reality (VR). We analyzed event related potentials (ERP), the event related spectral perturbation (ERSP) and the inter-trial coherence (ITC) from high-density EEG recording during video display onset (-200-600 ms) and the steady state visual evoked potentials (SSVEP) inside the video of human walking 3D-animation in three conditions: Normal; Upside-down (inverted images); and Uncoordinated (pseudo-randomly mixed images). We found that early visual evoked response P120 was decreased in Upside-down condition. The N170 and P300b amplitudes were decreased in Uncoordinated condition. In Upside-down and Uncoordinated conditions, we found decreased alpha power and theta phase-locking. As regards gamma oscillation, power was increased during the Upside-down animation and decreased during the Uncoordinated animation. An SSVEP-like response oscillating at about 10 Hz was also described showing that the oscillating pattern is enhanced 300 ms after the heel strike event only in the Normal but not in the Upside-down condition. Our results are consistent with most of previous point-light display studies, further supporting possible use of virtual reality for neurofeedback applications.
    Full-text · Article · Sep 2014 · Frontiers in Systems Neuroscience
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    ABSTRACT: In this study we employed a dynamic recurrent neural network (DRNN) in a novel fashion to reveal characteristics of control modules underlying the generation of muscle activations when drawing figures with the outstretched arm. We asked healthy human subjects to perform four different figure-eight movements in each of two workspaces (frontal plane and sagittal plane). We then trained a DRNN to predict the movement of the wrist from information in the EMG signals from seven different muscles. We trained different instances of the same network on a single movement direction, on all four movement directions in a single movement plane, or on all eight possible movement patterns and looked at the ability of the DRNN to generalize and predict movements for trials that were not included in the training set. Within a single movement plane, a DRNN trained on one movement direction was not able to predict movements of the hand for trials in the other three directions, but a DRNN trained simultaneously on all four movement directions could generalize across movement directions within the same plane. Similarly, the DRNN was able to reproduce the kinematics of the hand for both movement planes, but only if it was trained on examples performed in each one. As we will discuss, these results indicate that there are important dynamical constraints on the mapping of EMG to hand movement that depend on both the time sequence of the movement and on the anatomical constraints of the musculoskeletal system. In a second step, we injected EMG signals constructed from different synergies derived by the PCA in order to identify the mechanical significance of each of these components. From these results, one can surmise that discrete-rhythmic movements may be constructed from three different fundamental modules, one regulating the co-activation of all muscles over the time span of the movement and two others elliciting patterns of reciprocal activation operating in orthogonal directions.
    Full-text · Article · Sep 2014 · Frontiers in Computational Neuroscience
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    ABSTRACT: Owing to excellent time resolution and optimized spatial resolution related to increased number of recording electrodes, high-density electroencephalography allows localization of the sources of cortical activities evoked by specific stimulation. Here we evaluate the feasibility of a high-density EEG mismatch negativity of event-related potentials approach involving auditory cortical processing of phonemes in newborn infants born preterm (28 and 31 weeks’ gestation) in a routine clinical set-up. We recorded 64-channel EEG at term age. We identified the classical evoked components and found the amplitude of P1 and N2 to be significantly higher in the deviant (target) condition than in the standard condition. We analyzed the signals using standardized weighted low-resolution brain electromagnetic tomography (swLORETA) on theta, alpha, beta and gamma frequency bands. High theta and alpha power spectrum appeared in the superior and the middle temporal gyrus in following the standard and target stimulation. Additionally, delayed frontal area recruitment was seen after the target stimulation. Beta-gamma event-related synchronization was observed in BA10, BA46 and BA10, more markedly following target than standard stimulation. This suggests ability for auditory memory and change detection in neonates and shows early results in source localization. This approach paves the way for increased understanding of central processes involved during early neurological development. It may contribute to documenting physiological and deviant neurophysiological organization in the wider context of early diagnosis of features associated with preterm birth.
    Full-text · Article · Sep 2014
  • Bernard Dan

    No preview · Article · Sep 2014 · Developmental Medicine & Child Neurology
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    ABSTRACT: Background: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. Methods: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. Results: Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. Conclusions: Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.).
    Full-text · Article · Aug 2014 · New England Journal of Medicine
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    ABSTRACT: Background: The continuation of binge drinking is associated with the development of neurocognitive brain abnormalities similar to those observed in patients with alcohol dependence. Alcohol cue reactivity constitutes a risk marker for alcohol dependence. Through event-related potentials (ERPs), we aimed to examine its potential presence as well as its evolution over time in binge drinkers in a one-year period. Methods: ERPs were recorded during a visual oddball task in which controls (n=15) and binge drinkers (n=15) had to detect infrequent deviant stimuli (related or unrelated to alcohol) among frequent standard stimuli. The test was performed twice with a one-year interval in order to explore the long-lasting influence of drinking habits. Results: Contrary to the controls, binge drinkers showed significantly reduced amplitudes of the P1 component for both alcohol and non-alcohol-related cues and of the P3 component only for neutral cues in the second assessment compared with the first. Conclusion: The continuation of binge drinking over one year is associated with the development of brain functional abnormalities (indexed by the P1 component) as well as a higher reactivity to alcohol-related stimuli and/or a decreased reactivity to non-alcohol-related stimuli (indexed by the P3 component).
    Full-text · Article · Aug 2014 · Journal of Psychopharmacology
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    ABSTRACT: Non-convulsive status epilepticus is often challenging in paediatric practice. It is a treatable cause of cognitive deterioration and behavioural disturbances in many neurological conditions. It has a high association with Angelman syndrome, where differential electrodiagnosis with the typical non-epileptic rhythmic EEG patterns may be difficult. In this exploratory pilot study, we aimed to compare EEG patterns associated with non-convulsive status epilepticus in Angelman syndrome and other conditions. Participants and methods: EEG recordings obtained during nonconvulsive status epilepticus in three children with Angelman syndrome and four children with other conditions were retrospectively retrieved and analysed using ASA (Advance source of analysis).Results: In children with Angelman syndrome and nonconvulsive status epilepticus, the epileptic activity appeared mainly in the frontal regions as high-amplitude delta (6000-13000 ìV*2), theta (5000 ìV*2), alpha (1000 ìV*2) and beta (200-800 ìV*2) rhythms. In the other children, during non-convulsive status epilepticus, the epileptic mainly appeared in the centro-frontal regions as relatively lower amplitude delta (3000-6000 ìV*2), theta (1800 ìV*2), alpha (200 ìV*2) and beta (80 ìV*2). Cluster analysis showed segregation between the two groups. Conclusion: EEG associated with non-convulsive status epilepticus may have different electrogenetic properties in Angelman syndrome as compared with other conditions.
    Full-text · Conference Paper · Jul 2014

Publication Stats

5k Citations
615.94 Total Impact Points

Institutions

  • 2000-2015
    • Vrije Universiteit Brussel
      • Department of Neurology
      Bruxelles, Brussels Capital, Belgium
  • 1998-2015
    • Université Libre de Bruxelles
      • • Laboratory of Neurophysiology and Movement Biomechanics (LNMB)
      • • Faculty of Motricity Sciences (FMP)
      • • Department of Psychiatry
      • • Department of Nephrology and Urology
      Bruxelles, Brussels Capital, Belgium
  • 1995-2015
    • Hôpital Universitaire des Enfants Reine Fabiola
      • • Department of Neurology
      • • Department of Hemato-Oncology
      Bruxelles, Brussels Capital, Belgium
  • 1997-2014
    • University Hospital Brussels
      Bruxelles, Brussels Capital, Belgium
  • 2000-2010
    • University-Hospital Brugmann UVC
      Bruxelles, Brussels Capital, Belgium
  • 2004-2009
    • Université de Mons
      Mons, Walloon, Belgium
  • 2002
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      • Department of Neurophysiology
      Londinium, England, United Kingdom