Further characterisation of late somatosensory evoked potentials using electroencephalogram and magnetoencephalogram source imaging.

Beside the well-documented involvement of secondary somatosensory area, the cortical network underlying late somatosensory evoked potentials (P60/N60 and P100/N100) is still unknown. Electroencephalogram and magnetoencephalogram source imaging were performed to further investigate the origin of the brain cortical areas involved in late somatosensory evoked potentials, using sensory inputs of different strengths and by testing the correlation between cortical sources. Simultaneous high-density electroencephalograms and magnetoencephalograms were performed in 19 participants, and electrical stimulation was applied to the median nerve (wrist level) at intensity between 1.5 and 9 times the perceptual threshold. Source imaging was undertaken to map the stimulus-induced brain cortical activity according to each individual brain magnetic resonance imaging, during three windows of analysis covering early and late somatosensory evoked potentials. Results for P60/N60 and P100/N100 were compared with those for P20/N20 (early response). According to literature, maximal activity during P20/N20 was found in central sulcus contralateral to stimulation site. During P60/N60 and P100/N100, activity was observed in contralateral primary sensorimotor area, secondary somatosensory area (on both hemispheres) and premotor and multisensory associative cortices. Late responses exhibited similar characteristics but different from P20/N20, and no significant correlation was found between early and late generated activities. Specific clusters of cortical activities were activated with specific input/output relationships underlying early and late somatosensory evoked potentials. Cortical networks, partly common to and distinct from early somatosensory responses, contribute to late responses, all participating in the complex somatosensory brain processing.

Timing-specific patterns of cerebral activations during motor imagery: A case study of the expert brain signature.

Brain activations elicited during motor imagery (MI) in experts are typically reduced compared to novices, which is interpreted as a neurophysiological correlate of increased neural efficiency. However, the modulatory effects of MI speed on expertise-related differences in brain activation remains largely unknown. In the present pilot study, we compared the magnetoencephalographic (MEG) correlates of MI in an Olympic medallist and an amateur athlete under conditions of slow, real-time and fast MI. Data revealed event-related changes in the time course of alpha (8-12 Hz) power of MEG oscillations, for all timing conditions. We found that slow MI was associated with a corollary increase in neural synchronization, in both participants. Sensor-level and source-level analyses however disclosed differences between the two expertise levels. The Olympic medallist achieved greater activation of cortical sensorimotor networks than the amateur athlete, particularly during fast MI. Fast MI elicited the strongest event-related desynchronization of alpha oscillations, which was generated from cortical sensorimotor sources in the Olympic medallist, but not in the amateur athlete. Taken together, data suggest that fast MI is a particularly demanding form of motor cognition, putting a specific emphasis on cortical sensorimotor networks to achieve the formation of accurate motor representations under demanding timing constraints.

A New Generation of OPM for High Dynamic and Large Bandwidth MEG: The 4He OPMs-First Applications in Healthy Volunteers.

MagnetoEncephaloGraphy (MEG) provides a measure of electrical activity in the brain at a millisecond time scale. From these signals, one can non-invasively derive the dynamics of brain activity. Conventional MEG systems (SQUID-MEG) use very low temperatures to achieve the necessary sensitivity. This leads to severe experimental and economical limitations. A new generation of MEG sensors is emerging: the optically pumped magnetometers (OPM). In OPM, an atomic gas enclosed in a glass cell is traversed by a laser beam whose modulation depends on the local magnetic field. MAG4Health is developing OPMs using Helium gas (4He-OPM). They operate at room temperature with a large dynamic range and a large frequency bandwidth and output natively a 3D vectorial measure of the magnetic field. In this study, five 4He-OPMs were compared to a classical SQUID-MEG system in a group of 18 volunteers to evaluate their experimental performances. Considering that the 4He-OPMs operate at real room temperature and can be placed directly on the head, our assumption was that 4He-OPMs would provide a reliable recording of physiological magnetic brain activity. Indeed, the results showed that the 4He-OPMs showed very similar results to the classical SQUID-MEG system by taking advantage of a shorter distance to the brain, despite having a lower sensitivity.

Functional disconnection of associative cortical areas predicts performance during BCI training.

Brain-computer interfaces (BCIs) have been largely developed to allow communication, control, and neurofeedback in human beings. Despite their great potential, BCIs perform inconsistently across individuals and the neural processes that enable humans to achieve good control remain poorly understood. To address this question, we performed simultaneous high-density electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings in a motor imagery-based BCI training involving a group of healthy subjects. After reconstructing the signals at the cortical level, we showed that the reinforcement of motor-related activity during the BCI skill acquisition is paralleled by a progressive disconnection of associative areas which were not directly targeted during the experiments. Notably, these network connectivity changes reflected growing automaticity associated with BCI performance and predicted future learning rate. Altogether, our findings provide new insights into the large-scale cortical organizational mechanisms underlying BCI learning, which have implications for the improvement of this technology in a broad range of real-life applications.

Phase-amplitude coupling at the organism level: The amplitude of spontaneous alpha rhythm fluctuations varies with the phase of the infra-slow gastric basal rhythm.

A fundamental feature of the temporal organization of neural activity is phase-amplitude coupling between brain rhythms at different frequencies, where the amplitude of a higher frequency varies according to the phase of a lower frequency. Here, we show that this rule extends to brain-organ interactions. We measured both the infra-slow (~0.05Hz) rhythm intrinsically generated by the stomach - the gastric basal rhythm - using electrogastrography, and spontaneous brain dynamics with magnetoencephalography during resting-state with eyes open. We found significant phase-amplitude coupling between the infra-slow gastric phase and the amplitude of the cortical alpha rhythm (10-11Hz), with gastric phase accounting for 8% of the variance of alpha rhythm amplitude fluctuations. Gastric-alpha coupling was localized to the right anterior insula, and bilaterally to occipito-parietal regions. Transfer entropy, a measure of directionality of information transfer, indicates that gastric-alpha coupling is due to an ascending influence from the stomach to both the right anterior insula and occipito-parietal regions. Our results show that phase-amplitude coupling so far only observed within the brain extends to brain-viscera interactions. They further reveal that the temporal structure of spontaneous brain activity depends not only on neuron and network properties endogenous to the brain, but also on the slow electrical rhythm generated by the stomach.

Measuring neuronal avalanches to inform brain-computer interfaces.

Large-scale interactions among multiple brain regions manifest as bursts of activations called neuronal avalanches, which reconfigure according to the task at hand and, hence, might constitute natural candidates to design brain-computer interfaces (BCIs). To test this hypothesis, we used source-reconstructed magneto/electroencephalography during resting state and a motor imagery task performed within a BCI protocol. To track the probability that an avalanche would spread across any two regions, we built an avalanche transition matrix (ATM) and demonstrated that the edges whose transition probabilities significantly differed between conditions hinged selectively on premotor regions in all subjects. Furthermore, we showed that the topology of the ATMs allows task-decoding above the current gold standard. Hence, our results suggest that neuronal avalanches might capture interpretable differences between tasks that can be used to inform brain-computer interfaces.

Diverse beta burst waveform motifs characterize movement-related cortical dynamics.

Classical analyses of induced, frequency-specific neural activity typically average band-limited power over trials. More recently, it has become widely appreciated that in individual trials, beta band activity occurs as transient bursts rather than amplitude-modulated oscillations. Most studies of beta bursts treat them as unitary, and having a stereotyped waveform. However, we show there is a wide diversity of burst shapes. Using a biophysical model of burst generation, we demonstrate that waveform variability is predicted by variability in the synaptic drives that generate beta bursts. We then use a novel, adaptive burst detection algorithm to identify bursts from human MEG sensor data recorded during a joystick-based reaching task, and apply principal component analysis to burst waveforms to define a set of dimensions, or motifs, that best explain waveform variance. Finally, we show that bursts with a particular range of waveform motifs, ones not fully accounted for by the biophysical model, differentially contribute to movement-related beta dynamics. Sensorimotor beta bursts are therefore not homogeneous events and likely reflect distinct computational processes.

Helium Optically Pumped Magnetometers Can Detect Epileptic Abnormalities as Well as SQUIDs as Shown by Intracerebral Recordings.

Magnetoencephalography based on superconducting quantum interference devices (SQUIDs) has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited because of several constraints such as cost, fixed helmet size, and the obligation of immobility. A new generation of sensors, optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG [stereotactic EEG (SEEG)]. We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurologic diseases and fundamental neuroscience.

Tri-axial rubidium and helium optically pumped magnetometers for on-scalp magnetoencephalography recording of interictal epileptiform discharges: a case study.

Cryogenic magnetoencephalography (MEG) enhances the presurgical assessment of refractory focal epilepsy (RFE). Optically pumped magnetometers (OPMs) are cryogen-free sensors that enable on-scalp MEG recordings. Here, we investigate the application of tri-axial OPMs [87Rb (Rb-OPM) and 4He gas (He-OPM)] for the detection of interictal epileptiform discharges (IEDs). IEDs were recorded simultaneously with 4 tri-axial Rb- and 4 tri-axial He-OPMs in a child with RFE. IEDs were identified visually, isolated from magnetic background noise using independent component analysis (ICA) and were studied following their optimal magnetic field orientation thanks to virtual sensors. Most IEDs (>1,000) were detectable by both He- and Rb-OPM recordings. IEDs were isolated by ICA and the resulting magnetic field oriented mostly tangential to the scalp in Rb-OPMs and radial in He-OPMs. Likely due to differences in sensor locations, the IED amplitude was higher with Rb-OPMs. This case study shows comparable ability of Rb-OPMs and He-OPMs to detect IEDs and the substantial benefits of triaxial OPMs to detect IEDs from different sensor locations. Tri-axial OPMs allow to maximize spatial brain sampling for IEDs detection with a limited number of sensors.

Theta Band-Power Shapes Amyloid-Driven Longitudinal EEG Changes in Elderly Subjective Memory Complainers At-Risk for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) includes progressive symptoms spread along a continuum of preclinical and clinical stages. Although numerous studies uncovered the neuro-cognitive changes of AD, very little is known on the natural history of brain lesions and modifications of brain networks in elderly cognitively-healthy memory complainers at risk of AD for carrying pathophysiological biomarkers (amyloidopathy and tauopathy). OBJECTIVE: We analyzed resting-state electroencephalography (EEG) of 318 cognitively-healthy subjective memory complainers from the INSIGHT-preAD cohort at the time of their first visit (M0) and two-years later (M24). METHODS: Using 18F-florbetapir PET-scanner, subjects were stratified between amyloid negative (A-; n = 230) and positive (A+; n = 88) groups. Differences between A+ and A- were estimated at source-level in each band-power of the EEG spectrum. RESULTS: At M0, we found an increase of theta power in the mid-frontal cortex in A+ compared to A-. No significant association was found between mid-frontal theta and the individuals' cognitive performance. At M24, theta power increased in A+ relative to A- individuals in the posterior cingulate cortex and the pre-cuneus. Alpha band revealed a peculiar decremental trend in posterior brain regions in the A+ relative to the A- group only at M24. Theta power increase over the mid-frontal and mid-posterior cortices suggests an hypoactivation of the default-mode network in the A+ individuals and a non-linear longitudinal progression at M24. CONCLUSION: We provide the first source-level longitudinal evidence on the impact of brain amyloidosis on the EEG dynamics of a large-scale, monocentric cohort of elderly individuals at-risk for AD.

Somatosensory cortical remodelling after rehabilitation and clinical benefit of in writer's cramp.

In order to explore the pathophysiological basis of a new rehabilitation therapy in writer's cramp (WC), healthy controls, untreated WC patients and WC patients who recovered a legible handwriting after rehabilitation were explored using magnetoencephalography, and the somatosensory evoked fields of fingers I, II, III and V in the sensory cortex were studied. In the cortex controlling the dystonic limb, the size of the hand representation in the trained patients was similar to that of healthy controls, and significantly different from that of untrained patients. Trained patients exhibited 'super-normal' reorganisation of the finger maps. In the cortex controlling the non-dystonic limb, there was little difference between trained and untrained patients, and the hand representation was enlarged and disorganised. The authors hypothesise that prolonged tailored rehabilitation in WC may induce long-term plasticity phenomena, lateralised to the cortex controlling the dystonic hand.

Simultaneous MEG and intracranial EEG recordings during attentive reading.

The relationship between neural oscillations recorded at various spatial scales remains poorly understood partly due to an overall dearth of studies utilizing simultaneous measurements. In an effort to study quantitative markers of attention during reading, we performed simultaneous magnetoencephalography (MEG) and intracranial electroencephalography (iEEG) recordings in four epileptic patients. Patients were asked to attend to a specific color when presented with an intermixed series of red words and green words, with words of a given color forming a cohesive story. We analyzed alpha, beta, and gamma band oscillatory responses to the word presentation and compared the strength and spatial organization of those responses in both electrophysiological recordings. Time-frequency analysis of iEEG revealed a network of clear attention-modulated high gamma band (50-150 Hz) power increases and alpha/beta (9-25 Hz) suppressions in response to the words. In addition to analyses at the sensor level, MEG time-frequency analysis was performed at the source level using a sliding window beamformer technique. Strong alpha/beta suppressions were observed in MEG reconstructions, in tandem with iEEG effects. While the MEG counterpart of high gamma band enhancement was difficult to interpret at the sensor level in two patients, MEG time-frequency source reconstruction revealed additional activation patterns in accordance with iEEG results. Importantly, iEEG allowed us to confirm that several sources of gamma band modulation observed with MEG were indeed of cortical origin rather than EMG muscular or ocular artifact.

Integrating EEG and MEG Signals to Improve Motor Imagery Classification in Brain-Computer Interface.

We adopted a fusion approach that combines features from simultaneously recorded electroencephalogram (EEG) and magnetoencephalogram (MEG) signals to improve classification performances in motor imagery-based brain-computer interfaces (BCIs). We applied our approach to a group of 15 healthy subjects and found a significant classification performance enhancement as compared to standard single-modality approaches in the alpha and beta bands. Taken together, our findings demonstrate the advantage of considering multimodal approaches as complementary tools for improving the impact of noninvasive BCIs.

Disrupted core-periphery structure of multimodal brain networks in Alzheimer's disease.

In Alzheimer's disease (AD), the progressive atrophy leads to aberrant network reconfigurations both at structural and functional levels. In such network reorganization, the core and peripheral nodes appear to be crucial for the prediction of clinical outcome because of their ability to influence large-scale functional integration. However, the role of the different types of brain connectivity in such prediction still remains unclear. Using a multiplex network approach we integrated information from DWI, fMRI, and MEG brain connectivity to extract an enriched description of the core-periphery structure in a group of AD patients and age-matched controls. Globally, the regional coreness-that is, the probability of a region to be in the multiplex core-significantly decreased in AD patients as result of a random disconnection process initiated by the neurodegeneration. Locally, the most impacted areas were in the core of the network-including temporal, parietal, and occipital areas-while we reported compensatory increments for the peripheral regions in the sensorimotor system. Furthermore, these network changes significantly predicted the cognitive and memory impairment of patients. Taken together these results indicate that a more accurate description of neurodegenerative diseases can be obtained from the multimodal integration of neuroimaging-derived network data.

Time-frequency analysis reveals decreased high-frequency oscillations in writer's cramp.

High-frequency oscillations (HFO) have been suggested to reflect the activity of thalamocortical and/or intracortical neurons bursting at high frequencies. These circuits seem to be involved in pathophysiological mechanisms of focal dystonia. In healthy subjects, we characterized the spectrotemporal properties of HFO patterns evoked by dominant-hand median-nerve stimulation, using magnetoencephalography coupled with time-frequency analysis. Then, we investigated HFO in patients with writer's cramp and found that HFO patterns are strongly decreased in power and disorganized in time. This supports the assumption that abnormal HFOs reflect pathophysiological mechanisms occurring in focal dystonia, possibly resulting from a dysfunction of somatosensory processing.

Cortical correlates of illusory hand movement perception in humans: a MEG study.

The present study aimed to investigate cortical activity associated with perception of illusory hand movements elicited by tendon vibration using magnetoencephalography (MEG) in humans. We compared MEG responses in two conditions of stimulation, "illusion" and "no illusion". In the "illusion" condition, covibration at different frequencies applied on the tendons of the right wrist flexor and extensor muscle groups evoked illusory movements of the hand. In the "no illusion" condition, covibration was delivered at the same frequency on both tendon groups and no movement was perceived. In both experimental conditions, equivalent current dipoles (ECD) were identified in each of four time windows: 0-200 ms, 200-400 ms, 400-600 ms and 600-800 ms. Our data showed similar activation in S1, superior parietal gyrus and supramarginal gyrus in both conditions, whereas the supplementary motor area, M1 and the left angular gyrus were found active in the "illusion" condition only. Our results confirmed the role of posterior parietal areas as well as motor areas in the arising of kinesthetic sensations. The hypothesis of an interaction between the angular gyrus and the primary motor area occurring about 400 ms after the beginning of the stimulation is discussed.

Large-Scale Functional Networks Identified from Resting-State EEG Using Spatial ICA.

Several methods have been applied to EEG or MEG signals to detect functional networks. In recent works using MEG/EEG and fMRI data, temporal ICA analysis has been used to extract spatial maps of resting-state networks with or without an atlas-based parcellation of the cortex. Since the links between the fMRI signal and the electromagnetic signals are not fully established, and to avoid any bias, we examined whether EEG alone was able to derive the spatial distribution and temporal characteristics of functional networks. To do so, we propose a two-step original method: 1) An individual multi-frequency data analysis including EEG-based source localisation and spatial independent component analysis, which allowed us to characterize the resting-state networks. 2) A group-level analysis involving a hierarchical clustering procedure to identify reproducible large-scale networks across the population. Compared with large-scale resting-state networks obtained with fMRI, the proposed EEG-based analysis revealed smaller independent networks thanks to the high temporal resolution of EEG, hence hierarchical organization of networks. The comparison showed a substantial overlap between EEG and fMRI networks in motor, premotor, sensory, frontal, and parietal areas. However, there were mismatches between EEG-based and fMRI-based networks in temporal areas, presumably resulting from a poor sensitivity of fMRI in these regions or artefacts in the EEG signals. The proposed method opens the way for studying the high temporal dynamics of networks at the source level thanks to the high temporal resolution of EEG. It would then become possible to study detailed measures of the dynamics of connectivity.

Neuromagnetic imaging of cortical oscillations accompanying tactile stimulation.

We applied a new method of imaging frequency-specific changes in brain activity in humans during a finger brushing task in order to measure changes in cortical rhythms during tactile stimulation. Neuromagnetic recordings were conducted in five subjects using a whole-head MEG system during tactile stimulation of the right index finger, with or without visual feedback, and while viewing another individual's index finger being stimulated. Volumetric images of changes in source power relative to pre-stimulus baseline levels were computed with 2 mm resolution over the entire brain using a minimum-variance beamforming algorithm (synthetic aperture magnetometry). Onset of tactile stimulation produced a brief (200-300 ms) suppression of mu band (8-15 Hz) and beta band (15-30 Hz) cortical activity in the primary somatosensory and primary motor cortex, respectively, followed by a bilateral increase in beta band activity ('beta rebound') in motor cortex. This pattern of suppression/rebound was absent when subjects observed finger brushing or brushing motions without receiving stimulation. In contrast, these conditions resulted in bilateral increases in beta band activity in sensorimotor areas and decreased power in the alpha (8-12 Hz) band in primary visual areas. These results show that spatially filtered MEG provides a useful method for directly imaging the temporal sequence of changes in cortical rhythms during transient tactile stimulation, and provide evidence that observation of tactile input to another individual's hand, or object motion itself, can influence independent rhythmic activity in visual and sensorimotor cortex.

Assessment of subcortical source localization using deep brain activity imaging model with minimum norm operators: a MEG study.

Subcortical structures are involved in many healthy and pathological brain processes. It is crucial for many studies to use magnetoencephalography (MEG) to assess the ability to detect subcortical generators. This study aims to assess the source localization accuracy and to compare the characteristics of three inverse operators in the specific case of subcortical generators. MEG has a low sensitivity to subcortical sources mainly because of their distance from sensors and their complex cyto-architecture. However, we show that using a realistic anatomical and electrophysiological model of deep brain activity (DBA), the sources make measurable contributions to MEG sensors signals. Furthermore, we study the point-spread and cross-talk functions of the wMNE, sLORETA and dSPM inverse operators to characterize distortions in cortical and subcortical regions and to study how noise-normalization methods can improve or bias accuracy. We then run Monte Carlo simulations with neocortical and subcortical activations. In the case of single hippocampus patch activations, the results indicate that MEG can indeed localize the generators in the head and the body of the hippocampus with good accuracy. We then tackle the question of simultaneous cortical and subcortical activations. wMNE can detect hippocampal activations that are embedded in cortical activations that have less than double their amplitude, but it does not completely correct the bias to more superficial sources. dSPM and sLORETA can still detect hippocampal activity above this threshold, but such detection might include the creation of ghost deeper sources. Finally, using the DBA model, we showed that the detection of weak thalamic modulations of ongoing brain activity is possible.