Biology subjects

Michel, C. M.

Publications and source records attributed to Michel, C. M..

10 recordsLinked to original sources

bioRxiv2026

Progressive bilateral recruitment and resilient network reorganization during temporal lobe epilepsy

BackgroundTemporal lobe epilepsy (TLE) often originates from focal hippocampal injury but progressively evolves into a bilateral epileptic network engaging both hippocampi and distributed cortical regions. A mechanistic understanding of how this network emerges, and whether early perturbation of specific nodes can alter its trajectory, is essential for developing network-level therapeutic strategies. ObjectiveWe used a kainate-induced rodent model of TLE to (1) characterize the spatiotemporal emergence of epileptic discharges during the latent phase, (2) determine how bilaterally synchronized events develop, and (3) test whether transient chemogenetic silencing of either the ipsilateral epileptogenic focus (EF) or the contralateral hippocampus (CH) modifies large-scale epileptogenesis. MethodsFreely moving mice were implanted with multi-site electrodes spanning bilateral hippocampal subfields (dentate gyrus, CA1, subiculum) and cortical regions (M2, Cg1, PrL, V1, entorhinal cortex). Longitudinal LFP recordings were performed every other day during the latent and early chronic phases following KA or saline injection. DREADD-based chemogenetic inhibition of glutamatergic neurons was applied between days 2-7 post-KA. Epileptiform events were quantified via spike rates, waveform metrics, high-frequency oscillations (HFOs), and short-latency interregional co-spiking ResultsEarly after KA, epileptic spiking emerged locally in the ipsilateral dentate gyrus and progressively organized into HFO-coupled discharges. Contralateral hippocampal recruitment followed a distinctive biphasic time course, characterized by transient early activation, subsequent suppression, and later re-emergence with increasing bilateral coactivation. Cortical regions gradually developed higher spike rates and enhanced DG-related co-spiking, indicating large-scale network integration. Ipsilateral silencing modified local spike composition but did not prevent global network progression, whereas contralateral silencing accelerated ipsilateral epileptogenesis and strengthened pathological HFO expression. ConclusionEpileptogenesis in the KA model reflects a transition from a focal hippocampal insult to a resilient, bilateral cortico-hippocampal network. Targeting a single hippocampal node--even at early latent stages--is insufficient to halt this progression, highlighting the need for network-level therapeutic strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/701979v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@171797dorg.highwire.dtl.DTLVardef@df13d3org.highwire.dtl.DTLVardef@18e9594org.highwire.dtl.DTLVardef@1fe68f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Microstate Dynamics of Focused Attention Meditation

Focused-attention meditation provides a tractable model for examining how large-scale brain dynamics support attention and self-regulation. Using high-density EEG microstate analysis, we investigated how focused-attention meditation on the breath ([A]n[a]p[a]nasati) modulates intrinsic brain activity in 22 experienced practitioners, compared with baseline rest and deliberate mental imagery. Five canonical microstate classes (A-E) were identified. Meditation produced a robust reduction of Microstate C across coverage, duration, and occurrence, accompanied by increased presence of Microstates D and E (all Microstate x Condition interactions p < 0.0001). Source localization revealed that Microstate C was generated primarily in medial and lateral temporal regions including the hippocampus and parahippocampal cortex, whereas Microstate D involved posterior midline regions including the posterior cingulate cortex and precuneus, and Microstate E engaged frontoparietal and orbitolimbic networks. Together, these results indicate that focused-attention meditation reorganizes the temporal architecture of large-scale brain dynamics by downregulating microstate patterns associated with self-referential and memory-based processing while enhancing neural states supporting attentional stability and internal monitoring.

neuroscience↗

bioRxiv2023

Involvement of remote regions in sustained, but not transient, epileptic activities in the kainate mouse model of temporal lobe epilepsy

Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal or ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed since all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. We used surface, high-density EEG and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the well-known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and long-lasting discharges reminiscent of seizures. Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but while focus silencing abolishes all focal activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained epileptic discharges in the focus are preceded by contralateral firing and more strongly phase locked to bi-hippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting long-lasting, but not transient, epileptic activities. Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal-to ictal-state transition and proposes that cross-talk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short to long-lasting epileptic activities. Key PointsO_LIWe study how regions remote from the focus influence epileptic activities in the kainate mouse model of temporal lobe epilepsy. C_LIO_LIThe contralateral hippocampus plays a decisive role in the initiation of sustained epileptic activities C_LIO_LIIntegration of contralateral activities and bi-hippocampal delta/theta oscillations precedes focal paroxysmal activities C_LIO_LIWe propose that a large-scale epileptic network might be necessary for the transition from interictal to ictal states C_LI

neuroscience↗

bioRxiv2021

EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness

It is commonly believed that the stream of consciousness is not continuous but parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new method that estimates the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates temporal dynamics and complexity with increasing depth of sedation leading to a distinctive "U-shape" that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness. HighlightsO_LIEEG microstates capture discrete spatiotemporal patterns of global neuronal activity C_LIO_LIWe studied their temporal dynamics in relation to different states of consciousness C_LIO_LIWe introduce a new method to estimate the complexity of microstates sequences C_LIO_LIWith moderate sedation complexity increases then decreases with full sedation C_LIO_LIComplexity of microstate sequences is sensitive to altered states of consciousness C_LI

neuroscience↗

bioRxiv2021

Phase-amplitude coupling and phase synchronization between medial temporal, frontal and posterior brain regions support episodic autobiographical memory recall

Episodic autobiographical memory (EAM) is a complex cognitive function that emerges from the coordination of specific and distant brain regions. Specific brain rhythms, namely theta and gamma oscillations and their synchronization, are thought of as putative mechanisms enabling EAM. Yet, the mechanisms of inter-regional interaction in the EAM network remain unclear in humans at the whole brain level. To investigate this, we analyzed EEG recordings of participants instructed to retrieve autobiographical episodes. EEG recordings were projected in the source space, and time-courses of atlas-based brain regions-of-interest (ROIs) were derived. Directed phase synchrony in high theta (7-10 Hz) and gamma (30-80 Hz) bands and high theta-gamma phase-amplitude coupling were computed between each pair of ROIs. Using network-based statistics, a graph-theory method, we found statistically significant networks for each investigated mechanism. In the gamma band, two sub-networks were found, one between the posterior cingulate cortex (PCC) and the medial temporal lobe (MTL) and another within the medial frontal areas. In the high theta band, we found a PCC to ventromedial prefrontal cortex (vmPFC) network. In phase-amplitude coupling, we found the high theta phase of the left MTL biasing the gamma amplitude of posterior regions and the vmPFC. Other regions of the temporal lobe and the insula were also phase biasing the vmPFC. These findings suggest that EAM, rather than emerging from a single mechanism at a single frequency, involves precise spatio-temporal signatures mapping on distinct memory processes. We propose that the MTL orchestrates activity in vmPFC and PCC via precise phase-amplitude coupling, with vmPFC and PCC interaction via high theta phase synchrony and gamma synchronization contributing to bind information within the PCC-MTL sub-network or valuate the candidate memory within the medial frontal sub-network.

neuroscience↗

bioRxiv2021

Synchronous brain dynamics establish brief states of communality in distant neuronal populations

Intrinsic brain dynamics co-fluctuate between distant regions in an organized manner during rest, establishing large-scale functional networks. We investigate these brain dynamics on a millisecond time scale by focusing on Electroencephalographic (EEG) source analyses. While synchrony is thought of as a neuronal mechanism grouping distant neuronal populations into assemblies, the relevance of simultaneous zero-lag synchronization between brain areas in humans remains largely unexplored. This negligence is due to the confound of volume conduction, leading inherently to temporal dependencies of source estimates derived from scalp EEG (and Magnetoencephalography, MEG), referred to as spatial leakage. Here, we focus on the analyses of simultaneous, i.e., quasi zero-lag related, synchronization that cannot be explained by spatial leakage phenomenon. In eighteen subjects during rest with eyes closed, we provide evidence that first, simultaneous synchronization is present between distant brain areas and second, that this long-range synchronization is occurring in brief epochs, i.e., 54-80 milliseconds. Simultaneous synchronization might signify the functional convergence of remote neuronal populations. Given the simultaneity of distant regions, these synchronization patterns might relate to the representation and maintenance, rather than processing of information. This long-range synchronization is briefly stable, not persistently, indicating flexible spatial reconfiguration pertaining to the establishment of particular, re-occurring states. Taken together, we suggest that the balance between temporal stability and spatial flexibility of long-range, simultaneous synchronization patterns is characteristic of the dynamic coordination of large-scale functional brain networks. As such, quasi zero-phase related EEG source fluctuations are physiologically meaningful if spatial leakage is considered appropriately. SignificanceSynchrony is suggested as a mechanism for coordinating distant neuronal populations. Yet, simultaneous (i.e., zero-lag) synchronization between remote brain regions in humans is difficult to demonstrate, because volume conduction in EEG/MEG recordings causes spurious zero-lag relations. Here, we investigate actual zero-lag relations and systematically compare them to the residual bias due to spatial smoothness of EEG source estimates. We indeed report simultaneous synchronization between distant brain regions. These synchronization patterns manifest variably in time. We suggest that simultaneous synchronization is relevant when studying the dynamic, large-scale functional architecture in humans.

neuroscience↗

bioRxiv2020

Beyond broadband: towards a spectral decomposition of EEG microstates

Originally applied to alpha oscillations in the 1970s, MS analysis has since been used to decompose mainly broadband EEG signals (e.g. 1-40 Hz). We hypothesized that MS decomposition within separate, narrow frequency bands could provide more fine-grained information for capturing the spatio-temporal complexity of multichannel EEG. In this study using a large open-access dataset (n=203), we decomposed EEG recordings into 4 classical frequency bands (delta, theta, alpha, beta) in order to compare their individual MS segmentations using mutual information as well as traditional MS measures (e.g. mean duration, time coverage). Firstly, we confirmed that MS topographies were spatially equivalent across all frequencies, matching the canonical broadband maps (A, B, C, D). Interestingly however, we observed strong informational independence of MS temporal sequences between spectral bands, together with significant divergence in traditional MS measures. For example, relative to broadband, alpha/beta band dynamics displayed greater time coverage of maps A & B, while map D was more prevalent in delta/theta bands. Moreover, by using a frequency-specificMS taxonomy (e.g. {theta}A, C), we were able to predict the eyes-open vs closed-behavioural state significantly better using alpha-band MS features compared with broadband ones (80% vs 73% accuracy). Overall, our findings demonstrate the value and validity of spectrally-specific MS analyses, which may prove useful for identifying new neural mechanisms in fundamental research and/or for biomarker discovery in clinical populations.

neuroscience↗

bioRxiv2020

Early alterations of large-scale brain networkstemporal dynamics in young children with autism.

Disruption of large-scale brain networks is associated with autism spectrum disorders (ASD). Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD (Sperdin et al., 2018). Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 90 toddlers and preschoolers (47 with ASD) using an EEG microstate approach. Results revealed the presence of five microstate classes that best described the entire dataset (labeled as microstate classes A-E). Microstate class C related to the Default Mode Network (DMN) occurred less in children with ASD. Analysis of brain-behavioural relationships within the ASD group suggested that a compensatory mechanism from microstate C was associated with less severe symptoms and better adaptive skills. These results demonstrate that the temporal properties of some specific EEG microstates are altered in ASD at early developmental stages.

neuroscience↗

bioRxiv2018

Capturing the spatiotemporal dynamics of task-initiated thoughts with combined EEG and fMRI

When at rest, our mind wanders from thought to thought in distinct mental states. Despite the marked importance of ongoing mental processes, it is challenging to capture and relate these states to specific cognitive contents. In this work, we employed ultra-high field functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) to study the ongoing thoughts of participants instructed to retrieve self-relevant past episodes for periods of 20s. These task-initiated, participant-driven activity patterns were compared to a distinct condition where participants performed serial mental arithmetic operations, thereby shifting from self-related to self-unrelated thoughts. BOLD activity mapping revealed selective activity changes in temporal, parietal and occipital areas (\"posterior hot zone\"), evincing their role in integrating the re-experienced past events into conscious representations during memory retrieval. Functional connectivity analysis showed that these regions were organized in two major subparts of the default mode network, previously associated to \"scene-reconstruction\" and \"self-experience\" subsystems. EEG microstate analysis allowed studying these participant-driven thoughts in the millisecond range by determining the temporal dynamics of brief periods of stable scalp potential fields. This analysis revealed selective modulation of occurrence and duration of specific microstates in both conditions. EEG source analysis revealed similar spatial distributions between the sources of these microstates and the regions identified with fMRI. These findings support growing evidence that specific fMRI networks can be captured with EEG as repeatedly occurring, integrated brief periods of synchronized neuronal activity, lasting only fractions of seconds.\n\nSignificanceWe investigated the spatiotemporal dynamics of large-scale brain networks related to specific conscious thoughts. We demonstrate here that instructing participants to direct their thoughts to either episodic autobiographic memory or to mental arithmetic modulates distinct networks both in terms of highly spatially-specific BOLD signal oscillations as well as fast sub-second dynamics of EEG microstates. The combined findings from the two modalities evince a clear link between hemodynamic and electrophysiological signatures of spontaneous brain activity by the occurrence of thoughts that last for fractions of seconds, repeatedly appearing over time as integrated coherent activities of specific large-scale networks.

neuroscience↗

bioRxiv2017

Early alterations of social brain networks in young children with autism

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. Here, we recorded the gaze patterns and brain activity of toddlers and preschoolers with ASD and their typically developing (TD) peers while they explored dynamic social scenes. Source-space directed functional connectivity analyses revealed the presence of network alterations in the theta frequency band, manifesting as increased driving (hyper-activity) and stronger connections (hyper-connectivity) from key nodes of the social brain associated with autism. Further analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with lower clinical impairment and less atypical gaze patterns. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.

neuroscience↗