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We investigated the procedural learning deficit hypothesis in Developmental Coordination Disorder (DCD) while controlling for global performance such as slower reaction times (RTs) and variability. Procedural (sequence) learning was assessed in 31 children with DCD and 31 age-matched typically developing (TD) children through a serial reaction time task (SRTT). Sequential and random trial conditions were intermixed within five training epochs. Two repeated measures ANOVAs were conducted on a Sequence-Specific Learning Index (SSLI) and a Global Performance Index (GPI, speed/accuracy measure) with Epoch (for SSLI and GPI) and Condition (for GPI) as within-subjects factors, and Group as between-subjects factor. Controlling for RTs differences through normalized RTs, revealed a global reduction of SSLI in children with DCD compared with TD peers suggesting reduced sequence learning skills in DCD. Still, a significant Group x Condition interaction observed on GPI indicated that children from both groups were able to discriminate between sequential and random trials. DCD presented reduced procedural learning skills after controlling for global performance. This finding highlights the importance of considering the general functioning of the child while assessing learning skills in patients.

The ability to effectively and automatically regulate one's response to emotional information is a basic, fundamental skill for social functioning. The neural mechanisms underlying emotion regulation processing have been assessed, however few investigations have leveraged neurophysiological techniques, particularly magnetoencephalography (MEG) to determine the development of this critical ability. The current MEG study is the first to examine developmental changes in the neural mechanisms supporting automatic emotion regulation. We used an emotional go/no‐go task with happy and angry faces in a single‐site cohort of 97 healthy participants, 4–40 years of age. We found age‐related changes as a function of emotion and condition in brain regions key to emotion regulation, including the right inferior frontal gyrus, orbitofrontal cortices and primarily right‐lateralized temporal areas. Interaction effects, including an age by emotion and condition, were also found in the left angular gyrus, an area critical in emotion regulation and attention. Findings demonstrate protracted and nonlinear development, due to the adolescent group, of emotion regulation processing from child to adulthood, and highlight that age‐related differences in emotion regulation are modulated by emotional face type.

Post-learning slow wave sleep (SWS) is known to support declarative memory consolidation. As SWS is more abundant in young population, we suggested that sleep-dependent memory consolidation processes could occur at a faster pace in school-aged children. After learning new associations between non-objects and their functions, retrieval performance was tested in 30 children (7–12 years) and 34 adults (20–30 years) during an immediate (IR) and a delayed retrieval (DR) session separated by either a Sleep or a Wake condition. Sleep led to stabilized memory retrieval performance only in children, not in adults, whereas no age-related difference was observed after a similar period of wakefulness. Hence, our results suggest more efficient sleep-dependent declarative memory consolidation processes in children compared with adults, an effect potentially ascribed to more abundant and deeper SWS during childhood., SCOPUS: ar.j, info:eu-repo/semantics/published

This magnetoencephalography (MEG) study aimed at characterizing the spectro-temporal dynamics of brain oscillatory activity elicited by sentence completion (SC). For that purpose, we adapted a version of the SC experimental paradigm typically used in functional magnetic resonance imaging to MEG investigation constraints. Twenty right-handed healthy young adults underwent MEG recordings while they were sequentially presented with short sentences divided in three parts: the first two giving context and the last requiring completion. MEG data were then analysed using a prior-free, non-parametric statistical approach with stringent control of the family-wise error rate. We identified three successive significant neural response patterns associated with distinct spatial and spectro-temporal characteristics: (i) an early (800 ms) 8-30 Hz ERD involving the left dorsal language stream. Furthermore, the left component of the ventral language stream displayed prolonged ERD after 800 ms compared to the right which showed signs of inhibition in the form of ERS. Overall, this study elucidates the dynamics of the recruitment of the language network that accompany SC and the spectro-temporal signature of an extended semantic network. This MEG adaptation of an SC paradigm also paves the way for novel approaches in presurgical language mapping and may help to understand the neural underpinnings of the alterations of sentence completion in various neurologic disorders affecting language.

Children born very preterm (VPT, SCOPUS: ar.j, info:eu-repo/semantics/published

In previous studies we have provided evidence that performance in speeded response tasks with infrequent target stimuli reflects both automatic and controlled cognitive processes, based on differences in reaction time (RT) and task-related brain responses (Cheyne et al. 2012, Isabella et al. 2015). Here we test the hypothesis that such shifts in cognitive control may be influenced by changes in cognitive load related to stimulus predictability, and that these changes can be indexed by task-evoked pupillary responses (TEPR). We manipulated stimulus predictability using fixed stimulus sequences that were unknown to the participants in a Go/Switch task (requiring a switch response on 25% of trials) while monitoring TEPR as a measure of cognitive load in 12 healthy adults. Results showed significant improvement in performance (reduced RT, increased efficiency) for repeated sequences compared to occasional deviant sequences (10% probability) indicating that incidental learning of the predictable sequences facilitated performance. All behavioral measures varied between Switch and Go trials (RT, efficiency), however mean TEPR amplitude (mTEPR) and latency to maximum pupil dilation were particularly sensitive to Go/Switch. Results were consistent with the hypothesis that mTEPR indexes cognitive load, whereas TEPR latency indexes time to response selection, independent from response execution. The present study provides evidence that incidental pattern learning during response inhibition tasks may modulate several cognitive processes including cognitive load, effort, response selection and execution, which can in turn have differential effects on measures of performance. In particular, we demonstrate that reaction time may not be indicative of underlying cognitive load., SCOPUS: ar.j, info:eu-repo/semantics/published

This magnetoencephalography (MEG) study investigates how procedural sequence learning performance is related to prior brain resting-state functional connectivity (rsFC), and to what extent sequence learning induces rapid changes in brain rsFC in school-aged children. Procedural learning was assessed in 30 typically developing children (mean age ± SD: 9.99 years ± 1.35) using a serial reaction time task (SRTT). During SRTT, participants touched as quickly and accurately as possible a stimulus sequentially or randomly appearing in one of the quadrants of a touchscreen. Band-limited power envelope correlation (brain rsFC) was applied to MEG data acquired at rest pre- and post-learning. Correlation analyses were performed between brain rsFC and sequence-specific learning or response time indices. Stronger pre-learning interhemispheric rsFC between inferior parietal and primary somatosensory/motor areas correlated with better subsequent sequence learning performance and faster visuomotor response time. Faster response time was associated with post-learning decreased rsFC within the dorsal extra-striate visual stream and increased rsFC between temporo-cerebellar regions. In school-aged children, variations in functional brain architecture at rest within the sensorimotor network account for interindividual differences in sequence learning and visuomotor performance. After learning, rapid adjustments in functional brain architecture are associated with visuomotor performance but not sequence learning skills.

SCOPUS: le.j, info:eu-repo/semantics/published

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Human brain activity is not merely responsive to environmental context but includes intrinsic dynamics, as suggested by the discovery of functionally meaningful neural networks at rest, i.e., even without explicit engagement of the corresponding function. Yet, the neurophysiological coupling mechanisms distinguishing intrinsic (i.e., task-invariant) from extrinsic (i.e., task-dependent) brain networks remain indeterminate. Here, we investigated functional brain integration using magnetoencephalography throughout rest and various tasks recruiting different functional systems and modulating perceptual/cognitive loads. We demonstrated that two distinct modes of neural communication continually operate in parallel: extrinsic coupling supported by phase synchronization and intrinsic integration encoded in amplitude correlation. Intrinsic integration also contributes to phase synchronization, especially over short (second-long) timescales, through modulatory effects of amplitude correlation. Our study establishes the foundations of a novel conceptual framework for human brain function that fundamentally relies on electrophysiological features of functional integration. This framework blurs the boundary between resting-state and task-related neuroimaging.

Published online: 25 April 2018 Background. Electroencephalography (EEG) and magnetoencephalography (MEG) are neurophysiological methods used to investigate noninvasively the spatial, temporal, and spectral dynamics of human brain functions. Objectives. This article reviews data on the use of EEG and MEG for presurgical functional brainmapping in patients with refractory focal epilepsy. The focus is on the localization of the primary sensorimotor (SM1) cortex as well as the verbal language and episodic memory functions. Material andmethods. The English literature was reviewed based on a PubMed search. Relevant references in the selected papers were also included. Results. Presurgical MEG functional localization of the SM1 cortex generally overlaps with intracranial mapping. MEG allows for determination of hemispheric verbal (receptive and expressive) language dominance in neurosurgical patients with a high degree of concordance with the intracarotid amobarbital test. MEG represents an interesting technique for assessing postoperativememory outcome in patients withmesial temporal lobe epilepsy. Very few studies have evaluated the yield of EEG in these three clinical indications. High-density EEG might be a promising technique that needs further validation. Conclusion. MEG is a validated and robust technique for noninvasive functionalmapping of the SM1 cortex and verbal language hemispheric dominance in patients with refractory focal epilepsy. Current data also suggest that MEG is a promising technique for assessing the hemispheric dominance of memory function. Further studies are needed to assess the clinical added value of highdensity EEG in these clinical indications. T. Coolen is a Clinical Master Specialist Applicant to a PhD at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). A.M. Dumitrescu benefits from financial support of the Fonds Erasme (Research Convention “Les Voies du Savoir”, Brussels, Belgium). M. Bourguignon is supported by the program Attract of Innoviris (grant 2015- BB2B-10), by the Spanish Ministry of Economy and Competitiveness (grant PSI2016-77175-P), and by the Marie Skłodowska-Curie Action of the European Commission (grant 743562). X. De Tiège is Postdoctorate Clinical Master Specialist at the FRS-FNRS. The MEG project at the CUB Hôpital Erasme is financially supported by the Fonds Erasme (Research Convention “Les Voies du Savoir”).

Millions of North Americans sustain a concussion or a mild traumatic brain injury annually, and are at risk of cognitive, emotional, and physical sequelae. Although functional MRI (fMRI) studies have provided an initial framework for examining functional deficits induced by concussion, particularly working memory and attention, the temporal dynamics underlying these deficits are not well understood. We used magnetoencephalography (MEG), a modality with millisecond temporal resolution, in conjunction with a 1-back visual working memory (VWM) paradigm using scenes from everyday life to characterize spatiotemporal functional differences at specific VWM stages, in adults had had or had not had a recent concussion. MEG source-level differences between groups were determined by whole-brain analyses during encoding and recognition phases. Despite comparable behavioral performance, abnormal hypo- and hyperactivation patterns were found in brain areas involving frontoparietal, ventral occipitotemporal, temporal, and subcortical areas in concussed patients. These patterns and their timing varied as a function of VWM stagewise processing, linked to early attentional control, visuoperceptual scene processing, and VWM maintenance and retrieval processes. Parietal hypoactivation, starting at 60 ms during encoding, was correlated with symptom severity, possibly linked to impaired top-down attentional processing. Hyperactivation in the scene-selective occipitotemporal areas, the medial temporal complex, specifically the right hippocampus and orbitofrontal areas during encoding and/or recognition, lead us to posit inefficient but compensatory visuoperceptual, relational, and retrieval processing. Although injuries sustained after the concussion were considered "mild," these data suggest that they can have prolonged effects on early attentional and VWM processes.

Mechanisms for automatic emotion regulation (AER) are essential during childhood as they offset the impact of unwanted or negative emotional responses without drawing on limited attentional resources. Despite the importance of AER in improving the efficiency and flexibility of self-regulation, few research studies have investigated the underlying neurophysiological mechanisms. To fill this gap, we used magnetoencephalography (MEG) to investigate AER-related brain processes in 25 children (∼10 years old) who performed a go/no–go task that included an incidental exposure to faces containing socio-emotional cues. Whole brain results revealed that the inhibition of angry faces (compared with happy faces) was associated with a stronger recruitment of several brain regions from 100 to 425 ms. These activations involved the right angular and occipital gyri from 100 to175 ms, the right orbito-frontal gyrus (OFG) from 250 to 325 ms (pcorr, SCOPUS: ar.j, info:eu-repo/semantics/published

Children born very preterm (VPT) often demonstrate selective difficulties in working memory (WM), which may underlie academic difficulties observed in this population. Despite this, few studies have investigated the functional networks underlying WM in young children born VPT, a period when cognitive deficits become apparent. Using magnetoencephalography, we examined the networks underlying the maintenance of visual information in 6-year-old VPT (n = 15) and full-term (FT; n = 20) children. Although task performance was similar, VPT children engaged different oscillatory mechanisms during WM maintenance. Within the FT group, we observed higher mean whole-brain connectivity in the alpha-band during the retention (i.e. maintenance) interval associated with correct compared to incorrect responses. VPT children showed reduced whole-brain alpha synchrony, and a different network organization with fewer connections. In the theta-band, VPT children demonstrated a slight increase in whole-brain connectivity during WM maintenance, and engaged similar network hubs as FT children in the alpha-band, including the left dorsolateral prefrontal cortex and superior temporal gyrus. These findings suggest that VPT children rely on the theta-band to support similar task performance. Altered oscillatory mechanisms may reflect a less mature pattern of functional recruitment underlying WM in VPT children, which may affect the processing in complex ecological situations., info:eu-repo/semantics/published

Working Memory (WM) supports a wide range of cognitive functions, and is positively associated with academic achievement. Although fMRI studies have revealed WM networks in adults, little is known about how these networks develop to support successful WM performance in children. Using magnetoencephalography, we examined the networks underlying the maintenance of visual information in 6-year-old children. We observed an increase in mean whole-brain connectivity that was specific to the alpha frequency band during the retention interval associated with correct compared to incorrect responses. Additionally, our network analysis revealed elevated alpha synchronization during WM maintenance in a distributed network of frontal, parietal and temporal regions. Central hubs in the network were lateralized to the left hemisphere with dominant fronto-temporal connections, including the dorsolateral prefrontal cortex, middle temporal and superior temporal gyri, as well as other canonical language areas. Local changes in power were also analysed for seeds of interest, including the left inferior parietal lobe, which revealed an increase in alpha power after stimulus onset that was sustained throughout the retention period of WM. Our results therefore implicate sustained fronto-temporal alpha synchrony during the retention interval with subsequent successful WM responses in children, which may be aided by subvocal rehearsal strategies., SCOPUS: ar.j, info:eu-repo/semantics/published

Highlights • First MEG study of neural underpinnings of theory of mind differences in autism. • Children with autism show decreased LTPJ activity from 300 to 375 and 425 to 500 ms. • Children with autism also show increased RIFG activity from 325 to 375 ms. • Co-incident lower LTPJ and higher RIFG activity implies compensatory use of RIFG. • Executive functions may augment impaired theory of mind in autism., The social impairments observed in children with autism spectrum disorder are thought to arise in part from deficits in theory of mind, the ability to understand other people’s thoughts and feelings. To determine the temporal-spatial dynamics of brain activity underlying these atypical theory-of-mind processes, we used magnetoencephalography to characterize the sequence of functional brain patterns (i.e. when and where) related to theory-of-mind reasoning in 19 high-functioning children with autism compared to 22 age- and sex-matched typically-developing children aged 8–12 during a false-belief (theory-of-mind) task. While task performance did not differ between the two groups, children with autism showed reduced activation in the left temporoparietal junction between 300–375 and 425–500 ms, as well as increased activation in the right inferior frontal gyrus from 325 to 375 ms compared to controls. The overlap in decreased temporoparietal junction activity and increased right inferior frontal gyrus activation from 325 to 375 ms suggests that in children with autism, the right inferior frontal gyrus may compensate for deficits in the temporoparietal junction, a neural theory-of-mind network hub. As the right inferior frontal gyrus is involved in inhibitory control, this finding suggests that children with autism rely on executive functions to bolster their false-belief understanding.

OBJECTIVE To characterise the incidence, symptoms and risk factors for withdrawal associated with prolonged dexmedetomidine infusion in paediatric critically ill patients. METHODS Retrospective chart review in the paediatric intensive care unit and the cardiac critical care unit of a single tertiary children's hospital. Patients up to 18 years old, who received dexmedetomidine for longer than 48 hours were included. RESULTS A total of 52 patients accounted for 68 unique dexmedetomidine treatment courses of more than 48 hours. We identified 24 separate episodes of withdrawal in the 68 dexmedetomidine courses (incidence 35%). Of these episodes 38% occurred in patients who were weaned from dexmedetomidine alone while the remaining occurred in patients who had concurrent weans of opioids and/or benzodiazepines. Most common symptoms were agitation, fever, vomiting/retching, loose stools and decreased sleep. The symptoms occurred during the latter part of the wean or after discontinuation of dexmedetomidine. A cumulative dose of dexmedetomidine of 107 mcg/kg prior to initiation of wean was more likely associated with withdrawal (this equates to a dexmedetomidine infusion running at 1 mcg/kg/hr over 4 days). Duration of opioid use was an additional risk factor for withdrawal. The use of clonidine, as a transition from dexmedetomidine, did not protect against withdrawal (p = 1). CONCLUSIONS A withdrawal syndrome may occur after prolonged infusion of dexmedetomidine. As all our patients were also exposed to opioids this may be affected by the duration of opioid use. We identified a cumulative dose of 107 micrograms/kg of dexmedetomidine beyond which withdrawal symptoms were more likely (which equates to 4 days of use at a dose of 1 mcg/kg/hr). A protocol for weaning should be considered in this circumstance.

Background Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). Methods We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. Results We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps

That post-training sleep supports the consolidation of sequential motor skills remains debated. Performance improvement and sensitivity to proactive interference are both putative measures of long-term memory consolidation. We tested sleep-dependent memory consolidation for visuo-motor sequence learning using a proactive interference paradigm. Thirty-three young adults were trained on sequence A on Day 1, then had Regular Sleep (RS) or were Sleep Deprived (SD) on the night after learning. After two recovery nights, they were tested on the same sequence A, then had to learn a novel, potentially competing sequence B. We hypothesized that proactive interference effects on sequence B due to the prior learning of sequence A would be higher in the RS condition, considering that proactive interference is an indirect marker of the robustness of sequence A, which should be better consolidated over post-training sleep. Results highlighted sleep-dependent improvement for sequence A, with faster RTs overnight for RS participants only. Moreover, the beneficial impact of sleep was specific to the consolidation of motor but not sequential skills. Proactive interference effects on learning a new material at Day 4 were similar between RS and SD participants. These results suggest that post-training sleep contributes to optimizing motor but not sequential components of performance in visuo-motor sequence learning.

Emotion regulation mediates socio-cognitive functions and is essential for interactions with others. The capacity to automatically inhibit responses to emotional stimuli is an important aspect of emotion regulation; the underlying neural mechanisms of this ability have been rarely investigated. Forty adults completed a Go/No-go task during magnetoencephalographic (MEG) recordings, where they responded rapidly to either a blue or purple frame which contained angry or happy faces. Subjects responded to the target color in an inhibition (75% Go trials) and a vigilance condition (25% Go trials). As expected, inhibition processes showed early, sustained activation (200-450 ms) in the right inferior frontal gyrus (IFG). Emotion-related inhibition processes showed greater activity with angry faces bilaterally in the orbital-frontal gyri (OFG) starting at 225 ms and temporal poles from 250 ms, with right hemisphere dominance. The presence of happy faces elicited earlier activity in the right OFG. This study demonstrates that the timing of inhibition processes varies with the emotional context and that there is much greater activation in the presence of angry faces. It underscores the importance of the right IFG for inhibition processes, but the OFG in automatic emotion regulation.

Reporting the ink color of a written word when it is itself a color name incongruent with the ink color (e.g. "red" printed in blue) induces a robust interference known as the Stroop effect. Although this effect has been the subject of numerous functional neuroimaging studies, its neuronal substrate is still a matter of debate. Here, we investigated the spatiotemporal dynamics of interference-related neural events using magnetoencephalography (MEG) and voxel-based analyses (SPM8). Evoked magnetic fields (EMFs) were acquired in 12 right-handed healthy subjects performing a color-word Stroop task. Behavioral results disclosed a classic interference effect with longer mean reaction times for incongruent than congruent stimuli. At the group level, EMFs' differences between incongruent and congruent trials spanned from 380 to 700 ms post-stimulus onset. Underlying neural sources were identified in the left pre-supplementary motor area (pre-SMA) and in the left posterior parietal cortex (PPC) confirming the role of these regions in conflict processing., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Behavioral studies have cast doubts about the role that posttraining sleep may play in the consolidation of implicit sequence learning. Here, we used event-related fMRI to test the hypothesis that sleep-dependent functional reorganization would take place in the underlying neural circuits even in the possible absence of obvious behavioral changes. Twenty-four healthy human adults were scanned at Day 1 and then at Day 4 during an implicit probabilistic serial RT task. They either slept normally (RS) or were sleep-deprived (SD) on the first posttraining night. Unknown to them, the sequential structure of the material was based on a probabilistic finite-state grammar, with 15% chance on each trial of replacing the rules-based grammatical (G) stimulus with a nongrammatical (NG) one. Results indicated a gradual differentiation across sessions between RTs (faster RTs for G than NG), together with NG-related BOLD responses reflecting sequence learning. Similar behavioral patterns were observed in RS and SD participants at Day 4, indicating time- but not sleep-dependent consolidation of performance. Notwithstanding, we observed at Day 4 in the RS group a diminished differentiation between G- and NG-related neurophysiological responses in a set of cortical and subcortical areas previously identified as being part of the network involved in implicit sequence learning and its offline processing during sleep, indicating a sleep-dependent processing of both regular and deviant stimuli. Our results suggest the sleep-dependent development of distinct neurophysiological processes subtending consolidation of implicit motor sequence learning, even in the absence of overt behavioral differences.

Cognitive impairments are often associated with abnormal sleep activity in developmental disorders and pathologies of childhood. Besides, accumulated evidence indicates that post-training sleep benefits to the consolidation of recently learned information in healthy adults and children. Although sleep-dependent consolidation effects in children are clearly established for declarative memories, they remain more debated in the procedural memory domain. Nowadays, recent experimental data suggest close interactions between the development of sleep-dependent plasticity markers, cortical maturation and cognition in children. In the present review, we propose that studying sleep and memory consolidation processes in developmental disorders and acquired childhood pathologies can provide novel, enlightening clues to understand the pathophysiological mechanisms subtending the disruption of long-term cerebral plasticity processes eventually leading to cognitive and learning deficits in children.

Manual scoring of sleep spindles can be very time-consuming, and achieving accurate manual scoring on a long-term recording requires high and sustained levels of vigilance, which makes it a highly demanding task with the associated risk of decreased diagnosis accuracy. Although automatic spindle detection would be attractive, most available algorithms are sensitive to variations in spindle amplitude and frequency that occur between both subjects and derivations, reducing their effectiveness. We propose here an algorithm that models the amplitude-frequency spindle distribution with a bivariate normal distribution (one normal model per derivation). Subsequently, spindles are detected when their amplitude-frequency characteristics are included within a given tolerance interval of the corresponding model. As a consequence, spindle detection is not directly based on amplitude and frequency thresholds, but instead on a spindle distribution model that is automatically adapted to each individual subject and derivation. The algorithm was first assessed against the scoring of one sleep scoring expert on EEG samples from seven healthy children. Afterward, a second study compared performance of two additional experts versus the algorithm on a dataset of six EEG samples from adult patients suffering from different pathologies, to submit the method to more challenging and clinically realistic conditions. Smaller and shorter spindles were more difficult to evaluate, as false positives and false negatives showed lower amplitude and smaller length than true positives. In both studies, normal modelling enhanced performance compared to fixed amplitude and frequency thresholds. Normal modelling is therefore attractive, as it enhances spindle detection quality.

Available online 30 March 2016 Behavioral evidence shows that sleep is crucial for the consolidation of declarative memories in children as in adults. However, the underlying cerebral mechanisms remain virtually unexplored. Using magnetoencephalography, we investigated in children (8.0–12.5 years) the impact of sleep (90-minute nap) on the neurophysiological processes underlying the creation and consolidation of novel associations between unknown objects and their functions. Learning-dependent changes in brain activity were observed within hippocampal and parahippocampal regions, followed by sleep-dependent changes in the prefrontal cortex, whereas no equivalent change was observed after a similar period of wakeful rest. Hence, our results show that in school-age children a 90-minute daytime nap after learning is sufficient to trigger the reorganization of memory-related brain activity toward prefrontal areas, where it incorporates into pre-existing semantic knowledge. This functional reorganization process in children is similar to that observed in adults but occurs at a much faster rate, which may contribute to the development of the impressive learning skills that characterize childhood. This work was supported by a grant of the ULB-ARC (GD1844CX2720) project “Pathophysiology of Memory Consolidation Processes” and a grant from the Fondation Vigneron. Dr Xavier De Tiège was a post-doctorate clinical master specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium). Dr Vincent Wens is a post-doctorate logistic researcher at the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium).

It is hypothesised that focal interictal epileptiform discharges (IED) may exert a deleterious effect on behaviour and cognition in children. This hypothesis is supported by the abnormally high prevalence of IED in several developmental disorders, like specific language impairment, and of cognitive and behavioural deficits in epileptic children after excluding confounding factors such as underlying structural brain lesions, drug effects, or the occurrence of frequent or prolonged epileptic seizures. Neurophysiological and functional neuroimaging evidence suggests that IED may impact cognition through either transient effects on brain processing mechanisms, or through more long-lasting effects leading to prolonged inhibition of brain areas distant from but connected with the epileptic focus (i.e. remote inhibition effect). Sustained IED may also impair sleep-related learning consolidation processes. Nowadays, the benefits of anti-epileptic treatment aimed at reducing IED are not established except in specific situations like epileptic encephalopathies with continuous spike and waves during slow-wave sleep. Well-designed pharmacological studies are still necessary to address this issue., Journal Article, SCOPUS: sh.j, info:eu-repo/semantics/published

We investigated sleep-related declarative memory consolidation in four children with focal idiopathic epilepsy. In a population of healthy control children, recall of learned pairs of words was increased after a night of sleep, but not after a daytime wakefulness period. In children with epilepsy (1 case of benign epilepsy with centro-temporal spikes, 1 case of benign childhood epilepsy with occipital paroxysms, and 2 cases of epileptic encephalopathy (EE) with continuous spike and waves during slow-wave sleep, CSWS), recall performance significantly decreased overnight, suggesting impairment in sleep-related declarative memory consolidation. Hydrocortisone treatment in one patient with EE with CSWS resulted in normalization of the sleep EEG together with normalization of overnight memory performance, which was not the case in the other EE/CSWS patient whose sleep EEG was only partially improved. These preliminary results suggest that interictal epileptiform discharges in idiopathic focal epilepsies may disrupt the brain processes underlying sleep-related memory consolidation., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Theory of Mind (ToM) is the ability to understand the perspectives, mental states and beliefs of others in order to anticipate their behaviour and is therefore crucial to social interactions. Although fMRI has been widely used to establish the neural networks implicated in ToM, little is known about the timing of ToM-related brain activity. We used magnetoencephalography (MEG) to measure the neural processes underlying ToM, as MEG provides very accurate timing and excellent spatial localization of brain processes. We recorded MEG activity during a false belief task, a reliable measure of ToM, in twenty young adults (10 females). MEG data were recorded in a 151 sensor CTF system (MISL, Coquitlam, BC) and data were co-registered to each participant's MRI (Siemens 3T) for source reconstruction. We found stronger right temporoparietal junction (rTPJ) activations in the false belief condition from 150ms to 225ms, in the right precuneus from 275ms to 375ms, in the right inferior frontal gyrus from 200ms to 300ms and the superior frontal gyrus from 300ms to 400ms. Our findings extend the literature by demonstrating the timing and duration of neural activity in the main regions involved in the "mentalizing" network, showing that activations related to false belief in adults are predominantly right lateralized and onset around 100ms. The sensitivity of MEG will allow us to determine spatial and temporal differences in the brain processes in ToM in younger populations or those who demonstrate deficits in this ability.

Declarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep.A verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6-12 years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring.Overnight recall performance was lower in children with IFE than in control children on both tasks (ps0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike-wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps0.05).Memory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation.

Although a beneficial role of post-training sleep for declarative memory has been consistently evidenced in children, as in adults, available data suggest that procedural memory consolidation does not benefit from sleep in children. However, besides the absence of performance gains in children, sleep-dependent plasticity processes involved in procedural memory consolidation might be expressed through differential interference effects on the learning of novel but related procedural material. To test this hypothesis, 32 10-12-year-old children were trained on a motor rotation adaptation task. After either a sleep or a wake period, they were first retested on the same rotation applied at learning, thus assessing offline sleep-dependent changes in performance, then on the opposite (unlearned) rotation to assess sleep-dependent modulations in proactive interference coming from the consolidated visuomotor memory trace. Results show that children gradually improve performance over the learning session, showing effective adaptation to the imposed rotation. In line with previous findings, no sleep-dependent changes in performance were observed for the learned rotation. However, presentation of the opposite, unlearned deviation elicited significantly higher interference effects after post-training sleep than wakefulness in children. Considering that a definite feature of procedural motor memory and skill acquisition is the implementation of highly automatized motor behaviour, thus lacking flexibility, our results suggest a better integration and/or automation or motor adaptation skills after post-training sleep, eventually resulting in higher proactive interference effects on untrained material.

Learning the functional properties of objects is a core mechanism in the development of conceptual, cognitive and linguistic knowledge in children. The cerebral processes underlying these learning mechanisms remain unclear in adults and unexplored in children. Here, we investigated the neurophysiological patterns underpinning the learning of functions for novel objects in 10-year-old healthy children. Event-related fields (ERFs) were recorded using magnetoencephalography (MEG) during a picture-definition task. Two MEG sessions were administered, separated by a behavioral verbal learning session during which children learned short definitions about the "magical" function of 50 unknown non-objects. Additionally, 50 familiar real objects and 50 other unknown non-objects for which no functions were taught were presented at both MEG sessions. Children learned at least 75% of the 50 proposed definitions in less than one hour, illustrating children's powerful ability to rapidly map new functional meanings to novel objects. Pre- and post-learning ERFs differences were analyzed first in sensor then in source space. Results in sensor space disclosed a learning-dependent modulation of ERFs for newly learned non-objects, developing 500-800 msec after stimulus onset. Analyses in the source space windowed over this late temporal component of interest disclosed underlying activity in right parietal, bilateral orbito-frontal and right temporal regions. Altogether, our results suggest that learning-related evolution in late ERF components over those regions may support the challenging task of rapidly creating new semantic representations supporting the processing of the meaning and functions of novel objects in children. © 2013 Urbain et al., SCOPUS: ar.j, info:eu-repo/semantics/published