Spectrotemporal cortical dynamics and semantic control during sentence completion.

OBJECTIVE: To investigate cortical oscillations during a sentence completion task (SC) using magnetoencephalography (MEG), focusing on the semantic control network (SCN), its leftward asymmetry, and the effects of semantic control load. METHODS: Twenty right-handed adults underwent MEG while performing SC, consisting of low cloze (LC: multiple responses) and high cloze (HC: single response) stimuli. Spectrotemporal power modulations as event-related synchronizations (ERS) and desynchronizations (ERD) were analyzed: first, at the whole-brain level; second, in key SCN regions, posterior middle/inferior temporal gyri (pMTG/ITG) and inferior frontal gyri (IFG), under different semantic control loads. RESULTS: Three cortical response patterns emerged: early (0-200 ms) theta-band occipital ERS; intermediate (200-700 ms) semantic network alpha/beta-band ERD; late (700-3000 ms) dorsal language stream alpha/beta/gamma-band ERD. Under high semantic control load (LC), pMTG/ITG showed prolonged left-sided engagement (ERD) and right-sided inhibition (ERS). Left IFG exhibited heightened late (2500-2550 ms) beta-band ERD with increased semantic control load (LC vs. HC). CONCLUSIONS: SC involves distinct cortical responses and depends on the left IFG and asymmetric engagement of the pMTG/ITG for semantic control. SIGNIFICANCE: Future use of SC in neuromagnetic preoperative language mapping and for understanding the pathophysiology of language disorders in neurological conditions.

Motor learning- and consolidation-related resting state fast and slow brain dynamics across wake and sleep.

Motor skills dynamically evolve during practice and after training. Using magnetoencephalography, we investigated the neural dynamics underpinning motor learning and its consolidation in relation to sleep during resting-state periods after the end of learning (boost window, within 30 min) and at delayed time scales (silent 4 h and next day 24 h windows) with intermediate daytime sleep or wakefulness. Resting-state neural dynamics were investigated at fast (sub-second) and slower (supra-second) timescales using Hidden Markov modelling (HMM) and functional connectivity (FC), respectively, and their relationship to motor performance. HMM results show that fast dynamic activities in a Temporal/Sensorimotor state network predict individual motor performance, suggesting a trait-like association between rapidly recurrent neural patterns and motor behaviour. Short, post-training task re-exposure modulated neural network characteristics during the boost but not the silent window. Re-exposure-related induction effects were observed on the next day, to a lesser extent than during the boost window. Daytime naps did not modulate memory consolidation at the behavioural and neural levels. These results emphasise the critical role of the transient boost window in motor learning and memory consolidation and provide further insights into the relationship between the multiscale neural dynamics of brain networks, motor learning, and consolidation.

Towards the automated detection of interictal epileptiform discharges with magnetoencephalography.

BACKGROUND: The analysis of clinical magnetoencephalography (MEG) in patients with epilepsy traditionally relies on visual identification of interictal epileptiform discharges (IEDs), which is time consuming and dependent on subjective criteria. NEW METHOD: Here, we explore the ability of Independent Components Analysis (ICA) and Hidden Markov Modeling (HMM) to automatically detect and localize IEDs. We tested our pipelines on resting-state MEG recordings from 10 school-aged children with (multi)focal epilepsy. RESULTS: In focal epilepsy patients, both pipelines successfully detected visually identified IEDs, but also revealed unidentified low-amplitude IEDs. Success was more mitigated in patients with multifocal epilepsy, as our automated pipeline missed IED activity associated with some foci-an issue that could be alleviated by post-hoc manual selection of epileptiform ICs or HMM states. COMPARISON WITH EXISTING METHODS: We compared our results with visual IED detection by an experienced clinical magnetoencephalographer, getting heightened sensitivity and requiring minimal input from clinical practitioners. CONCLUSIONS: IED detection based on ICA or HMM represents an efficient way to identify IED localization and timing. The development of these automatic IED detection algorithms provide a step forward in clinical MEG practice by decreasing the duration of MEG analysis and enhancing its sensitivity.

How the Spreading and Intensity of Interictal Epileptic Activity Are Associated with Visuo-Spatial Skills in Children with Self-Limited Focal Epilepsy with Centro-Temporal Spikes.

This paper investigates brain-behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

Atypical procedural learning skills in children with Developmental Coordination Disorder.

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.

Atypical resting-state functional brain connectivity in children with developmental coordination disorder.

Children with developmental coordination disorder (DCD) present lower abilities to acquire and execute coordinated motor skills. DCD is frequently associated with visual perceptual (with or without motor component) impairments. This magnetoencephalography (MEG) study compares the brain resting-state functional connectivity (rsFC) and spectral power of children with and without DCD. 29 children with DCD and 28 typically developing (TD) peers underwent 2 × 5 min of resting-state MEG. Band-limited power envelope correlation and spectral power were compared between groups using a functional connectome of 59 nodes from eight resting-state networks. Correlation coefficients were calculated between fine and gross motor activity, visual perceptual and visuomotor abilities measures on the one hand, and brain rsFC and spectral power on the other hand. Nonparametric statistics were used. Significantly higher rsFC between nodes of the visual, attentional, frontoparietal, default-mode and cerebellar networks was observed in the alpha (maximum statistics, p = .0012) and the low beta (p = .0002) bands in children with DCD compared to TD peers. Lower visuomotor performance (copying figures) was associated with stronger interhemispheric rsFC within sensorimotor areas and power in the cerebellum (right lobule VIII). Children with DCD showed increased rsFC mainly in the dorsal extrastriate visual brain system and the cerebellum. However, this increase was not associated with their coordinated motor/visual perceptual abilities. This enhanced functional brain connectivity could thus reflect a characteristic brain trait of children with DCD compared to their TD peers. Moreover, an interhemispheric compensatory process might be at play to perform visuomotor task within the normative range.

Ignore the faces: Neural characterisation of emotional inhibition from childhood to adulthood using MEG.

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.

Resting-state functional brain connectivity is related to subsequent procedural learning skills in school-aged children.

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.

Frontoparietal Network Connectivity During an N-Back Task in Adults With Autism Spectrum Disorder.

BACKGROUND: Short-term and working memory (STM and WM) deficits have been demonstrated in individuals with autism spectrum disorder (ASD) and may emerge through atypical functional activity and connectivity of the frontoparietal network, which exerts top-down control necessary for successful STM and WM processes. Little is known regarding the spectral properties of the frontoparietal network during STM or WM processes in ASD, although certain neural frequencies have been linked to specific neural mechanisms. METHODS: We analysed magnetoencephalographic data from 39 control adults (26 males; 27.15 ± 5.91 years old) and 40 adults with ASD (26 males; 27.17 ± 6.27 years old) during a 1-back condition (STM) of an n-back task, and from a subset of this sample during a 2-back condition (WM). We performed seed-based connectivity analyses using regions of the frontoparietal network. Interregional synchrony in theta, alpha, and beta bands was assessed with the phase difference derivative and compared between groups during periods of maintenance and recognition. RESULTS: During maintenance of newly presented vs. repeated stimuli, the two groups did not differ significantly in theta, alpha, or beta phase synchrony for either condition. Adults with ASD showed alpha-band synchrony in a network containing the right dorsolateral prefrontal cortex, bilateral inferior parietal lobules (IPL), and precuneus in both 1- and 2-back tasks, whereas controls demonstrated alpha-band synchrony in a sparser set of regions, including the left insula and IPL, in only the 1-back task. During recognition of repeated vs. newly presented stimuli, adults with ASD exhibited decreased theta-band connectivity compared to controls in a network with hubs in the right inferior frontal gyrus and left IPL in the 1-back condition. Whilst there were no group differences in connectivity in the 2-back condition, adults with ASD showed no frontoparietal network recruitment during recognition, whilst controls activated networks in the theta and beta bands. CONCLUSIONS: Our findings suggest that since adults with ASD performed well on the n-back task, their appropriate, but effortful recruitment of alpha-band mechanisms in the frontoparietal network to maintain items in STM and WM may compensate for atypical modulation of this network in the theta band to recognise previously presented items in STM.

Frequency-specific neural synchrony in autism during memory encoding, maintenance and recognition.

Working memory impairment is associated with symptom severity and poor functional outcome in autistic individuals, and yet the neurobiology underlying such deficits is poorly understood. Neural oscillations are an area of investigation that can shed light on this issue. Theta and alpha oscillations have been found consistently to support working memory in typically developing individuals and have also been shown to be functionally altered in people with autism. While there is evidence, largely from functional magnetic resonance imaging studies, that neural processing underlying working memory is altered in autism, there remains a dearth of information concerning how sub-processes supporting working memory (namely encoding, maintenance and recognition) are impacted. In this study, we used magnetoencephalography to investigate inter-regional theta and alpha brain synchronization elicited during the widely used one-back task across encoding, maintenance and recognition in 24 adults with autism and 30 controls. While both groups performed comparably on the working-memory task, we found process- and frequency-specific differences in networks recruited between groups. In the theta frequency band, both groups used similar networks during encoding and recognition, but different networks specifically during maintenance. In comparison, the two groups recruited distinct networks across encoding, maintenance and recognition in alpha that showed little overlap. These differences may reflect a breakdown of coherent theta and alpha synchronization that supports mnemonic functioning, or in the case of alpha, impaired inhibition of task-irrelevant neural processing. Thus, these data provide evidence for specific theta and widespread alpha synchrony alterations in autism, and underscore that a detailed examination of the sub-processes that comprise working memory is warranted for a complete understanding of cognitive impairment in this population.

Author Correction: The power of children's sleep - Improved declarative memory consolidation in children compared with adults.

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

The power of children's sleep - Improved declarative memory consolidation in children compared with adults.

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.

Spectral slowing is associated with working memory performance in children born very preterm.

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.

Converging function, structure, and behavioural features of emotion regulation in very preterm children.

Children born very preterm (VPT; <32 weeks' gestational age) are at high risk for emotional regulation and social communication impairments. However, the underlying neurobiological correlates of these difficulties remain poorly understood. Using a multimodal approach, including both magnetoencephalographic and structural magnetic resonance imaging, we investigated the functional, structural, and behavioural characteristics of socio-emotional processing in 19 school-age children born VPT and 21 age-matched term-born (TB) children (7-13 years). Structural MRI analyses were conducted on a subset of these groups (16 VPT and 21 age-matched TB). Results showed that the inhibition of aversive socio-emotional stimuli was associated with a sustained reduction of right frontoparietal functional brain activity in children born VPT children. Moreover, whole brain structural analyses showed that reductions of cortical thickness or volume in these regions were associated with poor socio-emotional performance in children born VPT. Hence, our results suggest that functional and structural alterations encompassing the frontoparietal areas might be a biological marker of less efficient emotion regulation processes/performance in school-age children born VPT. These findings open up novel avenues to investigate the potential impact of such atypicalities, and in particular, those related to the atypical maturation of the medial prefrontal regions, on the frequent development of psychiatric disorders in this vulnerable population.

Pupillary responses and reaction times index different cognitive processes in a combined Go/Switch incidental learning task.

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.

Do you know what I'm thinking? Temporal and spatial brain activity during a theory-of-mind task in children with 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.

Alpha keeps it together: Alpha oscillatory synchrony underlies working memory maintenance in young children.

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.

Inhibition in the face of emotion: Characterization of the spatial-temporal dynamics that facilitate automatic emotion regulation.

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.