Riemannian classification of single-trial surface EEG and sources during checkerboard and navigational images in humans.

OBJECTIVE: Different visual stimuli are classically used for triggering visual evoked potentials comprising well-defined components linked to the content of the displayed image. These evoked components result from the average of ongoing EEG signals in which additive and oscillatory mechanisms contribute to the component morphology. The evoked related potentials often resulted from a mixed situation (power variation and phase-locking) making basic and clinical interpretations difficult. Besides, the grand average methodology produced artificial constructs that do not reflect individual peculiarities. This motivated new approaches based on single-trial analysis as recently used in the brain-computer interface field. APPROACH: We hypothesize that EEG signals may include specific information about the visual features of the displayed image and that such distinctive traits can be identified by state-of-the-art classification algorithms based on Riemannian geometry. The same classification algorithms are also applied to the dipole sources estimated by sLORETA. MAIN RESULTS AND SIGNIFICANCE: We show that our classification pipeline can effectively discriminate between the display of different visual items (Checkerboard versus 3D navigational image) in single EEG trials throughout multiple subjects. The present methodology reaches a single-trial classification accuracy of about 84% and 93% for inter-subject and intra-subject classification respectively using surface EEG. Interestingly, we note that the classification algorithms trained on sLORETA sources estimation fail to generalize among multiple subjects (63%), which may be due to either the average head model used by sLORETA or the subsequent spatial filtering failing to extract discriminative information, but reach an intra-subject classification accuracy of 82%.

Neural generators involved in visual cue processing in children with attention-deficit/hyperactivity disorder (ADHD).

Event-related potentials (ERP) studies report alterations in the ongoing visuo-attentional processes in children with attention-deficit/hyperactivity disorder (ADHD). We hypothesized that the neural generators progressively recruited after a cue stimulus imply executive-related areas well before engagement in executive processing in children with ADHD compared to typically developed children (TDC). We computed source localization (swLORETA) of the ERP and ERSP evoked by the Cue stimulus during a visual Cue-Go/Nogo paradigm in 15 ADHD compared to 16 TDC. A significant difference in N200/P200 amplitude over the right centro-frontal regions was observed between ADHD and TDC, supported by a stronger contribution of the left visuo-motor coordination area, premotor cortex, and prefrontal cortex in ADHD. In addition, we recorded a greater beta power spectrum in ADHD during the 80-230 ms interval, which was explained by increased activity in occipito-parieto-central areas and lower activity in the left supramarginal gyrus and prefrontal areas in ADHD. Successive analysis of the ERP generators (0-500 ms with successive periods of 50 ms) revealed significant differences beginning at 50 ms, with higher activity in the ventral anterior cingulate cortex, premotor cortex, and fusiform gyrus, and ending at 400-500 ms with higher activity of the dorsolateral prefrontal cortex and lower activity of the posterior cingulate cortex in ADHD compared to TDC. The areas contributing to ERP in ADHD and TDC differ from the early steps of visuo-attentional processing and reveal an overinvestment of the executive networks interfering with the activity of the dorsal attention network in children with ADHD.

EEG Dynamics of a Go/Nogo Task in Children with ADHD.

BACKGROUND: Studies investigating event-related potential (ERP) evoked in a Cue-Go/NoGo paradigm have shown lower frontal N1, N2 and central P3 in children with attention-deficit/hyperactivity disorder (ADHD) compared to typically developing children (TDC). However, the electroencephalographic (EEG) dynamics underlying these ERPs remain largely unexplored in ADHD. METHODS: We investigate the event-related spectral perturbation and inter-trial coherence linked to the ERP triggered by visual Cue-Go/NoGo stimuli, in 14 children (7 ADHD and 7 TDC) aged 8 to 12 years. RESULTS: Compared to TDC, the EEG dynamics of children with ADHD showed a lower theta-alpha ITC concomitant to lower occipito-parietal P1-N2 and frontal N1-P2 potentials in response to Cue, Go and Nogo stimuli; an upper alpha power preceding lower central Go-P3; a lower theta-alpha power and ITC were coupled to a lower frontal Nogo-N3; a lower low-gamma power overall scalp at 300 ms after Go and Nogo stimuli. CONCLUSION: These findings suggest impaired ability in children with ADHD to conserve the brain oscillations phase associated with stimulus processing. This physiological trait might serve as a target for therapeutic intervention or be used as monitoring of their effects.

Downregulation of the Glial GLT1 Glutamate Transporter and Purkinje Cell Dysfunction in a Mouse Model of Myotonic Dystrophy.

Brain function is compromised in myotonic dystrophy type 1 (DM1), but the underlying mechanisms are not fully understood. To gain insight into the cellular and molecular pathways primarily affected, we studied a mouse model of DM1 and brains of adult patients. We found pronounced RNA toxicity in the Bergmann glia of the cerebellum, in association with abnormal Purkinje cell firing and fine motor incoordination in DM1 mice. A global proteomics approach revealed downregulation of the GLT1 glutamate transporter in DM1 mice and human patients, which we found to be the result of MBNL1 inactivation. GLT1 downregulation in DM1 astrocytes increases glutamate neurotoxicity and is detrimental to neurons. Finally, we demonstrated that the upregulation of GLT1 corrected Purkinje cell firing and motor incoordination in DM1 mice. Our findings show that glial defects are critical in DM1 brain pathophysiology and open promising therapeutic perspectives through the modulation of glutamate levels.

Short-term EEG dynamics and neural generators evoked by navigational images.

The ecological environment offered by virtual reality is primarily supported by visual information. The different image contents and their rhythmic presentation imply specific bottom-up and top-down processing. Because these processes already occur during passive observation we studied the brain responses evoked by the presentation of specific 3D virtual tunnels with respect to 2D checkerboard. For this, we characterized electroencephalograhy dynamics (EEG), the evoked potentials and related neural generators involved in various visual paradigms. Time-frequency analysis showed modulation of alpha-beta oscillations indicating the presence of stronger prediction and after-effects of the 3D-tunnel with respect to the checkerboard. Whatever the presented image, the generators of the P100 were situated bilaterally in the occipital cortex (BA18, BA19) and in the right inferior temporal cortex (BA20). In checkerboard but not 3D-tunnel presentation, the left fusiform gyrus (BA37) was additionally recruited. P200 generators were situated in the temporal cortex (BA21) and the cerebellum (lobule VI/Crus I) specifically for the checkerboard while the right parahippocampal gyrus (BA36) and the cerebellum (lobule IV/V and IX/X) were involved only during the 3D-tunnel presentation. For both type of image, P300 generators were localized in BA37 but also in BA19, the right BA21 and the cerebellar lobule VI for only the checkerboard and the left BA20-BA21 for only the 3D-tunnel. Stronger P300 delta-theta oscillations recorded in this later situation point to a prevalence of the effect of changing direction over the proper visual content of the 3D-tunnel. The parahippocampal gyrus (BA36) implicated in navigation was also identified when the 3D-tunnel was compared to their scrambled versions, highlighting an action-oriented effect linked to navigational content.

EEG Spectral Generators Involved in Motor Imagery: A swLORETA Study.

In order to characterize the neural generators of the brain oscillations related to motor imagery (MI), we investigated the cortical, subcortical, and cerebellar localizations of their respective electroencephalogram (EEG) spectral power and phase locking modulations. The MI task consisted in throwing a ball with the dominant upper limb while in a standing posture, within an ecological virtual reality (VR) environment (tennis court). The MI was triggered by the visual cues common to the control condition, during which the participant remained mentally passive. As previously developed, our paradigm considers the confounding problem that the reference condition allows two complementary analyses: one which uses the baseline before the occurrence of the visual cues in the MI and control resting conditions respectively; and the other which compares the analog periods between the MI and the control resting-state conditions. We demonstrate that MI activates specific, complex brain networks for the power and phase modulations of the EEG oscillations. An early (225 ms) delta phase-locking related to MI was generated in the thalamus and cerebellum and was followed (480 ms) by phase-locking in theta and alpha oscillations, generated in specific cortical areas and the cerebellum. Phase-locking preceded the power modulations (mainly alpha-beta ERD), whose cortical generators were situated in the frontal BA45, BA11, BA10, central BA6, lateral BA13, and posterior cortex BA2. Cerebellar-thalamic involvement through phase-locking is discussed as an underlying mechanism for recruiting at later stages the cortical areas involved in a cognitive role during MI.

Brain Oscillations in Sport: Toward EEG Biomarkers of Performance.

Brain dynamics is at the basis of top performance accomplishment in sports. The search for neural biomarkers of performance remains a challenge in movement science and sport psychology. The non-invasive nature of high-density electroencephalography (EEG) recording has made it a most promising avenue for providing quantitative feedback to practitioners and coaches. Here, we review the current relevance of the main types of EEG oscillations in order to trace a perspective for future practical applications of EEG and event-related potentials (ERP) in sport. In this context, the hypotheses of unified brain rhythms and continuity between wake and sleep states should provide a functional template for EEG biomarkers in sport. The oscillations in the thalamo-cortical and hippocampal circuitry including the physiology of the place cells and the grid cells provide a frame of reference for the analysis of delta, theta, beta, alpha (incl.mu), and gamma oscillations recorded in the space field of human performance. Based on recent neuronal models facilitating the distinction between the different dynamic regimes (selective gating and binding) in these different oscillations we suggest an integrated approach articulating together the classical biomechanical factors (3D movements and EMG) and the high-density EEG and ERP signals to allow finer mathematical analysis to optimize sport performance, such as microstates, coherency/directionality analysis and neural generators.

Long-Lasting Cortical Reorganization as the Result of Motor Imagery of Throwing a Ball in a Virtual Tennis Court.

In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto-central delta and contralateral central mu to parietal theta presented here.

Gravity influences top-down signals in visual processing.

Visual perception is not only based on incoming visual signals but also on information about a multimodal reference frame that incorporates vestibulo-proprioceptive input and motor signals. In addition, top-down modulation of visual processing has previously been demonstrated during cognitive operations including selective attention and working memory tasks. In the absence of a stable gravitational reference, the updating of salient stimuli becomes crucial for successful visuo-spatial behavior by humans in weightlessness. Here we found that visually-evoked potentials triggered by the image of a tunnel just prior to an impending 3D movement in a virtual navigation task were altered in weightlessness aboard the International Space Station, while those evoked by a classical 2D-checkerboard were not. Specifically, the analysis of event-related spectral perturbations and inter-trial phase coherency of these EEG signals recorded in the frontal and occipital areas showed that phase-locking of theta-alpha oscillations was suppressed in weightlessness, but only for the 3D tunnel image. Moreover, analysis of the phase of the coherency demonstrated the existence on Earth of a directional flux in the EEG signals from the frontal to the occipital areas mediating a top-down modulation during the presentation of the image of the 3D tunnel. In weightlessness, this fronto-occipital, top-down control was transformed into a diverging flux from the central areas toward the frontal and occipital areas. These results demonstrate that gravity-related sensory inputs modulate primary visual areas depending on the affordances of the visual scene.

DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation.

Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology.

Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials.

BACKGROUND: Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG) activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP) triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. RESULTS: The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25-35 Hz) and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25-35 Hz) peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. CONCLUSION: The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.