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This magnetoencephalography study aimed at characterizing age-related changes in resting-state functional brain organization from mid-childhood to late adulthood. We investigated neuromagnetic brain activity at rest in 105 participants divided into three age groups: children (6–9 years), young adults (18–34 years) and healthy elders (53–78 years). The effects of age on static resting-state functional brain integration were assessed using band-limited power envelope correlation, whereas those on transient functional brain dynamics were disclosed using hidden Markov modeling of power envelope activity. Brain development from childhood to adulthood came with (1) a strengthening of functional integration within and between resting-state networks and (2) an increased temporal stability of transient (100–300 ms lifetime) and recurrent states of network activation or deactivation mainly encompassing lateral or medial associative neocortical areas. Healthy aging was characterized by decreased static resting-state functional integration and dynamic stability within the primary visual network. These results based on electrophysiological measurements free of neurovascular biases suggest that functional brain integration mainly evolves during brain development, with limited changes in healthy aging. These novel electrophysiological insights into human brain functional architecture across the lifespan pave the way for future clinical studies investigating how brain disorders affect brain development or healthy aging., info:eu-repo/semantics/published

Detecting predators is essential for survival. Given that snakes are the first of primates’ major predators, natural selection may have fostered efficient snake detection mechanisms to allow for optimal defensive behavior. Here, we provide electrophysiological evidence for a brain-anchored evolved predisposition to rapidly detect snakes in humans, which does not depend on previous exposure or knowledge about snakes. To do so, we recorded scalp electrical brain activity in 7- to 10-month-old infants watching sequences of flickering animal pictures. All animals were presented in their natural background. We showed that glancing at snakes generates specific neural responses in the infant brain, that are higher in amplitude than those generated by frogs or caterpillars, especially in the occipital region of the brain. The temporal dynamics of these neural responses support that infants devote increased attention to snakes than to non-snake stimuli. These results therefore demonstrate that a single fixation at snakes is sufficient to generate a prompt and large selective response in the infant brain. They argue for the existence in humans of an inborn, brain-anchored mechanism to swiftly detect snakes based on their characteristic visual features., info:eu-repo/semantics/published

Magnetoencephalography (MEG) is an established method to investigate epilepsy. Current MEG systems house hundreds of cryogenic sensors in a rigid, one-size-fits-all helmet, which results in several limitations, particularly in children. On-scalp MEG based on optically-pumped magnetometers (OPMs) may alleviate these limitations.We report on five children (5–11 years old) with self-limited focal (n=3) or structural (n=2) epilepsy who underwent cryogenic (102 magnetometers) and on-scalp (32 OPMs) MEG. We compared the two modalities for the detection and localization of interictal epileptiform discharges (IEDs).We identified IEDs in all children with comparable sensor topographies for both MEG devices. IED amplitudes were 2.3-4.8 times higher with on-scalp MEG and signal-to-noise ratio (SNR) was also 27-60% higher with on-scalp MEG in all but one patient with large head movement artifacts. The neural source of averaged IEDs was located at about 5 mm (n=3) or higher (8.3 mm, n=1; 15.6 mm, n=1) between on-scalp and cryogenic MEG.Despite limited number of sensors and scalp coverage, on-scalp MEG detects IEDs in epileptic children with higher SNR than cryogenic MEG. This technology, which is in constant development, should become a reference in the diagnostic workup of epilepsy and replace cryogenic MEG in the near future.

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer's disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with subjective cognitive decline (SCD), 10 patients with amnestic mild cognitive impairment (aMCI) and 10 patients with typical Alzheimer’s disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. Correlations were sought between temporal properties of HMM states and participants' cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores, nor with the whole hippocampal volume. However, it correlated positively with the regional glucose consumption in the right dorsolateral prefrontal cortex (DLPFC). AD patients present alterations of posterior DMN power activation dynamics at rest that identify an additional electrophysiological correlate of AD-related synaptic and neural dysfunction. The right DLPFC may play a causal role in the activation of the posterior DMN, possibly linked to the occurrence of mind wandering episodes. As such, these data might suggest a neural correlate of the decrease in mind wandering episodes reported in pathological aging., info:eu-repo/semantics/published

Working memory (WM) problems are frequently present in people with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a visual‐verbal 2‐back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event‐related fields and theta (4–8 Hz) and alpha (8–13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = .014). This theta power increase value correlated negatively with reaction time on the task in MS (r = −.32, p = .029). Evidence was provided that this relationship could not be explained by a ‘common cause’ confounding relationship with MS‐related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS., This study is the first to provide neurophysiological evidence of impaired hippocampal WM processing in MS that can be related to WM performance. Our data suggests that impaired theta oscillatory processes in the right hippocampus, supposedly underlying WM encoding, lead to slower reaction times on the task. We also provide evidence that this relationship cannot be accounted for by general MS‐related neural damage (specifically hippocampal and white matter damage).

info:eu-repo/semantics/published

The mismatch negativity (MMN) reflects the early detection of changes in sensory stimuli at the cortical level. The mechanisms underlying its genesis remain debated. This magnetoencephalography study investigates the spatio-temporal dynamics and the neural mechanisms of the magnetic somatosensory MMN. Somatosensory evoked magnetic fields elicited by tactile stimulation of the right fingertip (Single), tactile stimulation of the right middle phalanx and fingertip (Double) or omissions (Omitted) of tactile stimuli were studied in different paradigms: in oddballs where Double/Omitted followed a sequence of four Single, in sequences of two stimuli where Double occurred after one Single, and in random presentation of Double only. The predictability of Double occurrence in oddballs was also manipulated. Cortical sources of evoked responses were identified using equivalent current dipole modeling. Evoked responses elicited by Double were significantly different from those elicited by Single at the contralateral secondary somatosensory (cSII) cortex. Double elicited higher cSII cortex responses than Single when preceded by a sequence of four Single, compared to when they were preceded by one Single. Double elicited higher cSII cortex response when presented alone compared to when Double were preceded by one or a sequence of Single. Omitted elicited similar cSII cortex response than Single. Double in oddballs led to higher cSII cortex responses when less predictable. These data suggest that early tactile change detection involves mainly cSII cortex. The predictive coding framework probably accounts for the SII cortex response features observed in the different tactile paradigms., SCOPUS: ar.j, info:eu-repo/semantics/published

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

This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences., SCOPUS: ar.j, info:eu-repo/semantics/published

Summary Aims of the study This study investigates the effect of movement rate on the coupling between cortical magnetoencephalographic (MEG) signals and the kinematics of repetitive active finger movements, i.e., the corticokinematic coherence (CKC). Material and methods CKC was evaluated in ten right-handed healthy adults performing repetitive flexion–extension of the right-hand fingers in three different movement rate conditions: slow (∼1 Hz, duration: 11 min), medium (∼2 Hz, duration: 5 min) and fast (∼3 Hz, duration: 3 min). Neuromagnetic signals were recorded with a whole-scalp-covering MEG (Elekta Oy) and index acceleration was monitored with a 3-axis accelerometer. Coherent sources were estimated on the time-course of the cross-correlogram using equivalent current dipole (ECD) modeling. Results Significant coherence was found at movement frequency or its first harmonics in all subjects and movement conditions. ECDs clustered at the primary sensorimotor cortex contralateral to hand movements. Movement rate had no effect on the coherence levels and the location of coherent sources. Conclusions This study demonstrates that the movement rate does not affect coherence levels and CKC source location during active finger movements. This finding has direct implications for CKC functional mapping applications and studies investigating the pathophysiology of central nervous disorders affecting proprioceptive pathways.

Functional magnetic resonance imaging (fMRI) studies report age-related changes in resting-state functional connectivity (rsFC), suggesting altered or reorganized connectivity patterns with age. However, age-related changes in neurovascular coupling might also partially account for altered connectivity patterns. Here, we used resting-state magnetoencephalography (MEG) and a connectome approach in carefully selected healthy young adults and elders. The MEG connectome was estimated as rsFC matrices involving forty nodes from six major resting-state networks. Source-level rsFC maps were computed in relevant frequency bands using leakage-corrected envelope correlations. Group differences were statistically assessed using non-parametric permutation tests. Our results failed to evidence significant age-related differences after correction for multiple comparisons in the α and the β bands both for static and dynamic rsFC, suggesting that the electrophysiological connectome is maintained in healthy ageing. Further studies should compare the evolution of the human brain connectome as estimated using fMRI and MEG in same healthy young and elder adults, as well as in ageing conditions associated with cognitive decline. At present, our results are in agreement with the brain maintenance theory for successful aging as they suggest that preserved intrinsic functional brain integration contributes to preserved cognitive functioning in healthy elders., SCOPUS: ar.j, info:eu-repo/semantics/published

This study investigates whether movement kinematics modulates similarly the rolandic α and β rhythm amplitude during executed and observed goal-directed hand movements. It also assesses if this modulation relates to the corticokinematic coherence (CKC), which is the coupling observed between cortical activity and movement kinematics during such motor actions. Magnetoencephalography (MEG) signals were recorded from 11 right-handed healthy subjects while they performed or observed an actor performing the same repetitive hand pinching action. Subjects' and actor's forefinger movements were monitored with an accelerometer. Coherence was computed between acceleration signals and the amplitude of α (8-12 Hz) or β (15-25 Hz) oscillations. The coherence was also evaluated between source-projected MEG signals and their β amplitude. Coherence was mainly observed between acceleration and the amplitude of β oscillations at movement frequency within bilateral primary sensorimotor (SM1) cortex with no difference between executed and observed movements. Cross-correlation between the amplitude of β oscillations at the SM1 cortex and movement acceleration was maximal when acceleration was delayed by ~ 100 ms, both during movement execution and observation. Coherence between source-projected MEG signals and their β amplitude during movement observation and execution was not significantly different from that during rest. This study shows that observing others' actions engages in the viewer's brain similar dynamic modulations of SM1 cortex β rhythm as during action execution. Results support the view that different neural mechanisms might account for this modulation and CKC. These two kinematic-related phenomena might help humans to understand how observed motor actions are actually performed., SCOPUS: ar.j, info:eu-repo/semantics/published

In the Stroop task, incongruent stimuli (e.g. “red” printed in blue) induce a robust interference effect. The impact of both the changes in the duration of the interval between the subject’s response and the next stimulus (RSI) and the development from childhood to adulthood on the size of the interference have not been systematically studied. We have therefore tested the modulation of within-task RSI (from 1000 to 5000 ms) on the interference effect in 8–10 years old children and young adults. Results disclose a stronger interference effect for the shortest RSI duration (1000 ms) in both adults and children, indicating more effective inhibitory processses for longer RSI durations. Moreover, similar interference effect were found between children and adults suggesting that both groups are similarly affected by interference. Taken together, these results suggest that inhibitory processes require a certain amount of time to develop.

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

When evaluating children with mental retardation, subtle cerebral and cerebellar morphologic anomalies are often noted at Magnetic Resonance Imaging (MRI). Some, such as cerebellar cortical dysplasia (CCD), have been considered as subtle markers of cerebral dysgenesis. Their functional significance and their effect on brain function, remain unknown. To study supratentorial functional disturbances related to CCD we performed Positron-Emission-Tomography (PET) studies in two children with isolated CCD, in order to investigate the degree of involvement of supratentorial structures. One had developmental delay, motor disturbances and ataxia, and the other one only had mental retardation. PET studies revealed hypoperfusion and hypometabolism within the vermis, thalamus and the right striatum in one case, and hypometabolism in the basal ganglia and cerebellar deep grey nuclei in the other case. Our results could lead to a hypothesis explaining motor disturbances as well as cognitive impairment, and could suggest a pathological functional significance of CCD. Nevertheless, the relationship between these findings and mental retardation needs further investigation.

Comatose, vegetative, minimally conscious or locked-in patients represent a problem in terms of diagnosis, prognosis, treatment and everyday management at the intensive care unit. The evaluation of possible cognitive functions in these patients is difficult because voluntary movements may be very small, inconsistent and easily exhausted. Functional neuroimaging cannot replace the clinical assessment of patients with altered states of consciousness. Nevertheless, it can describe objectively how deviant from normal the cerebral activity is and its regional distribution at rest and under various conditions of stimulation. The quantification of brain activity differentiates patients who sometimes only differ by a brief and incomplete blink of an eye. In the present paper, we will first try to define consciousness as it can be assessed at the patient's bedside. We then review the major clinical entities of altered states of consciousness encountered in the intensive care unit. Finally, we discuss the functional neuroanatomy of these conditions as assessed by positron emission tomography (PET) scanning.

A high density of 5-HT1a receptors is present in pyramidal hippocampal cells. Mapping of these receptors may be performed in vivo using the tracer no-carrier-added 4-(18)F-fluoro-N-2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl-N-2-pyridinyl-benzamide (MPPF). We tested the hypothesis of a relationship between MPPF binding and post-epileptic neuronal loss in the hippocampus. The model of limbic epilepsy induced by kainic acid (KA) in the rat was used. Rats were sacrificed at various times (1 h-240 days) after systemic injection of 10 mg/kg KA. Determination of MPPF binding in the brain was combined with a quantification of neuronal loss using DNA labeling with propidium iodide and confocal microscopy. Hippocampal MPPF binding varied according to time elapsed from KA injection. An initial decrease from day 1 to day 6 post injection was followed by a relative increase between day 6 and day 30. This effect was observed in rats which showed hippocampal neuronal loss but also in one rat which did not. In KA treated rats, statistically significant relationship between MPPF binding and neuronal count was found during the acute period (rats sacrificed 1 h-day 6 after KA injection) and the chronic phase (rats sacrificed beyond day 60 after KA injection). The late relative increase of MPPF binding suggests an epilepsy-induced increase of 5-HT1a receptors in the hippocampus. This effect needs to be further characterized before considering PET determination of hippocampal MPPF binding as a method of post-epileptic neuronal loss assessment., Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

OBJECTIVES: The purpose of this study is to determine the factors influencing the spatial precision and the replicability of electromagnetic trackers (EMT) for the localization of electrodes and natural landmarks on the patient's head. MATERIALS AND METHODS: The effects of seven conditions on the measurement of the EMT were investigated with a Polhemus Fastrack: distance, contact between two components of the EMT, presence of magnetic object, localization of landmarks and electrodes on a phantom and a human subject without and with movements. RESULTS: The EMT has a precision of 0.15mm+/-0.36mm for the measurements made on still objects in a non-magnetic environment. On a human subject, the mean variation of the nasion position is 1.6mm+/-1.46mm and 2.7mm+/-1.40mm for the tragus. The increase of the electrode measurement dispersions is significant between the phantom and the human subject with a mean variation of 2.39mm+/-1.26mm. In certain conditions, up to 15% of the measurements may be considered as outliers. CONCLUSION: The precision significantly decreases for this application in the following cases: (1) physical contacts between the stylus/transmitter/receiver cables, (2) presence of magnetic objects in the surrounding of the EMT system, (3) skin and hair softness and (4) subject's head movements., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND AND PURPOSE: This study aimed to investigate brain maturation along gestational age with diffusion tensor imaging in healthy preterm and term neonates. Therefore, a voxel-based study of fractional anisotropy (FA) and mean diffusivity (D(av)) was performed to reveal the brain regions experiencing microstructural changes with age. With tractography, the authors intended to identify which fiber tracts were included in these significant voxels. MATERIALS AND METHODS: There were 22 healthy preterm and 6 healthy term infants who underwent MR imaging between 34 and 41 weeks of gestation. A statistical parametric approach was used to evidence the effect of age on regional distribution of FA and D(av) values. The fiber tracts suspected to be included in the significant clusters of voxels were identified with neuroanatomy and tractography atlases, reconstructed with probabilistic tractography, and superimposed on the parametric maps. RESULTS: Parametric analysis showed that FA increases with age in the subcortical projections from the frontal (motor and premotor areas) and parietal cortices, the centrum semiovale, the anterior and posterior arms of the internal capsules, the optic radiations, the corpus callosum, and the thalami (P < .05, corrected). Superimposition of the parametric maps on tractography showed that the corticospinal tract (CST); the callosal radiations (CR); and the superior, anterior, and posterior thalamic radiations were included in the significant voxels. No statistically significant results were found for D(av) maps. CONCLUSIONS: These results highlight that, besides the already-evidenced FA increase in the CST and CR, the thalami and the thalamic radiations experience microstructural changes in the early development of the human brain., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Comatose, vegetative, minimally conscious or locked-in patients represent a problem in terms of diagnosis, prognosis, treatment and everyday management at the intensive care unit. The evaluation of possible cognitive functions in these patients is difficult because voluntary movements may be very small, inconsistent and easily exhausted. Functional neuroimaging cannot replace the clinical assessment of patients with altered states of consciousness. Nevertheless, it can describe objectively how deviant from normal the cerebral activity is and its regional distribution at rest and under various conditions of stimulation. The quantification of brain activity differentiates patients who sometimes only differ by a brief and incomplete blink of an eye. In the present paper, we will first try to define consciousness as it can be assessed at the patient's bedside. We then review the major clinical entities of altered states of consciousness encountered in the intensive care unit. Finally, we discuss the functional neuroanatomy of these conditions as assessed by positron emission tomography (PET) scanning.

BACKGROUND: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. METHODS: Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (SPM). First, each patient was compared with a control group and the influence of age, epileptic activity, and corticosteroid treatment on metabolic abnormalities was studied. Also, disease-related changes in the contribution of a brain area to the level of metabolic activity in another brain area were investigated using pathophysiologic interactions in groups of patients compared with the control group. RESULTS: Individual SPM analyses identified three metabolic patterns: association of hypermetabolic and hypometabolic areas, hypometabolic areas only, and normal pattern. Age and intensity of awake interictal spiking did not significantly differ in patients showing focal hypermetabolism compared with the other ones. Treatment with corticosteroids was associated with absence of focal hypermetabolism. In the group of patients with hypermetabolic areas, analyses of pathophysiologic interactions showed disease-related altered functional connectivity between the parietal and frontal cortices. CONCLUSIONS: Cerebral metabolic patterns are heterogeneous among patients with CSWS. This metabolic heterogeneity could be related to the use of corticosteroid treatment before PET. The parietofrontal altered connectivity observed in patients with hypermetabolism is interpreted as a phenomenon of remote inhibition of the frontal lobes induced by highly epileptogenic and hypermetabolic posterior cortex., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Relapses of herpes simplex encephalitis (HSE) occurring after the completion of antiviral treatment have been reported repeatedly in children. The authors report data on six children who had at least one relapse of HSE. Two different mechanisms may account for these relapses, including viral replication or an immuno-inflammatory process, with different therapeutic attitudes. Relapses with viral replication may reveal host susceptibility to herpes simplex virus infection., Comparative Study, Journal Article Ces auteurs ont contribué de manière équivalente à cette étude, info:eu-repo/semantics/published

Corticokinematic coherence (CKC) refers to coupling between magnetoencephalographic (MEG) brain activity and hand kinematics. For voluntary hand movements, CKC originates mainly from the primary sensorimotor (SM1) cortex. To learn about the relative motor and sensory contributions to CKC, we recorded CKC from 15 healthy subjects during active and passive right index-finger movements. The fingertip was either touching or not touching table, resulting in active-touch, active-no-touch, passive-touch, and passive-no-touch conditions. The kinematics of the index-finger was measured with a 3-axis accelerometer. Beamformer analysis was used to locate brain activations for the movements; somatosensory-evoked fields (SEFs) elicited by pneumatic tactile stimulation of the index finger served as a functional landmark for cutaneous input. All active and passive movements resulted in statistically significant CKC at the movement frequency (F0) and its first harmonic (F1). The main CKC sources at F0 and F1 were in the contralateral SM1 cortex with no spatial differences between conditions, and distinct from the SEF sources. At F1, the coherence was by two thirds stronger for passive than active movements, with no difference between touch vs. no-touch conditions. Our results suggest that the CKC occurring during repetitive finger movements is mainly driven by somatosensory, primarily proprioceptive, afferent input to the SM1 cortex, with negligible effect of cutaneous input., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published