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O'Byrne, J.

Publications and source records attributed to O'Byrne, J..

7 recordsLinked to original sources

Local mechanical heterogeneity drives epidermal cell delamination

Delamination within stratified epithelia like the skin epidermis describes the detachment and upward motion of cells originating from the basal layer. Despite its fundamental importance for tissue development, homeostatic regeneration and repair, the mechanisms that drive delamination remain a longstanding open question. Upward motion follows cell shape changes, which are inherently driven by physical forces, but their role is elusive. Here, we investigate delamination in stratifying keratinocytes by combining imaging, force measurements and theoretical modeling. We identify a local change in force balance between differentiating cells and their environment as the key step initiating delamination. Within a homogeneous cell layer with apically polarized contractility, differentiation leads to actomyosin remodeling, redistributing cellular force exertion to the basal side. Such mechanical heterogeneity then results in differentiating cells experiencing and inward basal and outward apical forces that manifest in the formation of a +1 force defect and promote shape changes culminating in upward motion. Simultaneously, delaminating cells actively pull on their underlying neighbors, generating convergent tissue flows which close the basal layer below. Together, we propose a general physical description of delamination initiation, which may act across various multilayered epithelia.

biophysics↗

Critical dynamics in spontaneous EEG predict perturbational complexity in disorders of consciousness with measurable evoked responses

Identifying which severely brain-injured patients retain the capacity for consciousness remains a major challenge in neurocritical care. The perturbational complexity index (PCI) provides a reliable assessment of consciousness capacity, but its reliance on transcranial magnetic stimulation and EEG (TMS-EEG) limits bedside scalability. PCI and brain criticality capture complementary dimensions of brain dynamics: PCI quantifies the complexity of the brains evoked response to perturbation, whereas criticality characterizes the intrinsic organization of spontaneous activity. Here, we tested whether resting-state EEG signatures of criticality predict PCImax in disorders of consciousness, extending prior findings from anesthesia to severe brain injury. In 26 patients with vascular, traumatic, or anoxic brain injury, multivariate criticality related features did not generalize PCImax prediction across the full heterogeneous cohort. However, criticality features predicted PCImax when analyses were restricted to non-anoxic patients and when restricting analyses to patients with non-zero PCImax values. These findings suggest that spontaneous criticality measures index the brains intrinsic dynamical regime that supports complex perturbational responses, while their correspondence with PCImax depends on whether the injured brain retains sufficient capacity to sustain large-scale evoked responses. Together, our results extend the relationship between resting-state criticality and evoked perturbational complexity to disorders of consciousness and support the development of stratified EEG measures in severe brain injury.

neuroscience↗

Meditation induces shifts in neural oscillations, braincomplexity and critical dynamics: Novel insights fromMEG

While the beneficial impacts of meditation are increasingly acknowledged, its underlying neural mechanisms remain poorly understood. We examined the electrophysiological brain signals of expert Buddhist monks during two established meditation methods known as Samatha and Vipassana, which employ focused attention and open monitoring technique. By combining source-space magnetoencephalography (MEG) with advanced signal processing and machine learning tools, we provide an unprecedented assessment of the role of brain oscillations, complexity and criticality in meditation. In addition to power spectral density (PSD), we computed long-range temporal correlations (LRTC), deviation from criticality coefficient (DCC), Lempel-Ziv complexity (LZC), 1/f slope, Higuchi fractal dimension (HFD), and spectral entropy. Our findings indicate increased levels of neural signal complexity during both meditation practices compared to the resting state, along-side widespread reductions in gamma-band LRTC and 1/f slope. Importantly, the DCC analysis revealed a separation between Samatha and Vipassana, suggesting that their distinct phenomenological properties are mediated by specific computational characteristics of their dynamic states. Furthermore, in contrast to most previous reports, we observed a decrease in oscillatory gamma power during meditation, a divergence we attribute to the correction of the power spectrum by the 1/f slope. We discuss how these results advance our comprehension of the neural processes associated with focused attention and open monitoring meditation practices.

neuroscience↗

Scale-free flocking and giant fluctuations in epithelial active solids

The collective motion of epithelial cells is a fundamental biological process which plays a significant role in embryogenesis, wound healing and tumor metastasis. While it has been broadly investigated for over a decade both in vivo and in vitro, large scale coherent flocking phases remain underexplored and have so far been mostly described as fluid. In this work, we report a mode of large-scale collective motion for different epithelial cell types in vitro with distinctive new features. By tracking individual cells, we show that cells move over long time scales coherently not as a fluid, but as a polar elastic solid with negligible cell rearrangements. Our analysis reveals that this solid flocking phase exhibits signatures of long-range polar order, unprecedented in cellular systems, with scale-free correlations, anomalously large density fluctuations, and shear waves. Based on a general theory of active polar solids, we argue that these features result from massless Goldstone modes, which, in contrast to polar fluids where they are generic, require the decoupling of global rotations of the polarity and in-plane elastic deformations in polar solids. We theoretically show and consistently observe in experiments that the fluctuations of elastic deformations diverge for large system size in such polar active solid phases, leading eventually to rupture and thus potentially loss of tissue integrity at large scales. Significance statementDuring embryonic development and wound healing, epithelial cells usually display in-plane polarity over large spatial scales and move coherently. However, over years, most in vitro studies have examined the fluid-like chaotic dynamics of epithelial cells, in which collective cellular flows self-organize into recurring transient vortices and jets similar to those observed in classical fluid turbulence. Little is known about the large-scale coherent dynamics of epithelial cells. We demonstrate that such coherent motions are not simply turbulent-like flows with larger correlation lengths, but a new mode of collective motion with a solid-like behavior, accompanied by an emergent global order, scale-free correlations, anomalous density fluctuations and propagating Goldstone modes. Our work suggests that such a collective motion of epithelial cells falls outside the scope of traditional active fluids, which may shed new light on the current studies of collective cell migration as well as active matter physics.

biophysics↗

Phase-amplitude coupling of NREM sleep oscillations is unaffected by pre-sleep learning but related to overnight memory gains depending on the declarative learning paradigm

There is growing evidence in humans linking the temporal coupling between spindles and slow oscillations during NREM sleep with the overnight stabilization of memories encoded from daytime experiences in humans. However, whether the type and strength of learning influence that relationship is still unknown. Here we tested whether the amount or type of verbal word-pair learning prior to sleep affects subsequent phase-amplitude coupling (PAC) between spindles and slow oscillations (SO). We measured the strength and preferred timing of such coupling in the EEG of 41 healthy human participants over a post-learning and control night, to compare intra-individual changes with inter-individual differences. We leveraged learning paradigms of varying word-pair (WP) load: 40 WP learned to a minimum criterion of 60% correct (n=11); 40 WP presented twice (n=15); 120 WP presented twice (n=15). There were no significant differences in the preferred phase or strength between the control and post-learning nights, in all learning conditions. We observed an overnight consolidation effect (improved performance at delayed recall) for the criterion learning condition only, and only in this condition was the overnight change in memory performance significantly positively correlated with the phase of SO-spindle coupling. These results suggest that the coupling of brain oscillations during human NREM sleep are stable traits that are not modulated by the amount of pre-sleep learning, yet are implicated in the sleep-dependent consolidation of memory.

neuroscience↗

Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia

1Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness. 2 Significance StatementComplexity has long been of interest in consciousness science and had a fundamental impact on many of todays theories of consciousness. The perturbational complexity index (PCI) uses the complexity of the brains response to cortical perturbations to quantify the presence of consciousness. We propose criticality as a unifying framework underlying maximal complexity and sensitivity to perturbation in the conscious brain. We demonstrate that criticality measures derived from resting-state electroencephalography can distinguish conscious from unconscious states, using propofol, xenon and ketamine anesthesia, and from these measures we were able to predict the PCI with a mean error below 7%. Our results support the hypothesis that critical brain dynamics are implicated in the emergence of consciousness and may provide new directions for the assessment of consciousness.

neuroscience↗

Class imbalance should not throw you off balance: Choosing classifiers and performance metrics for brain decoding with imbalanced data

Machine learning (ML) is increasingly used in cognitive, computational and clinical neuroscience. The reliable and efficient application of ML requires a sound understanding of its subtleties and limitations. Training ML models on datasets with imbalanced classes is a particularly common problem, and it can have severe consequences if not adequately addressed. With the neuroscience ML user in mind, this paper provides a didactic assessment of the class imbalance problem and illustrates its impact through systematic manipulation of data imbalance ratios in (i) simulated data and (ii) brain data recorded with electroencephalography (EEG) and magnetoencephalography (MEG). Our results illustrate how the widely-used Accuracy (Acc) metric, which measures the overall proportion of successful predictions, yields misleadingly high performances, as class imbalance increases. Because Acc weights the per-class ratios of correct predictions proportionally to class size, it largely disregards the performance on the minority class. A binary classification model that learns to systematically vote for the majority class will yield an artificially high decoding accuracy that directly reflects the imbalance between the two classes, rather than any genuine generalizable ability to discriminate between them. We show that other evaluation metrics such as the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC), and the less common Balanced Accuracy (BAcc) metric - defined as the arithmetic mean between sensitivity and specificity, provide more reliable performance evaluations for imbalanced data. Our findings also highlight the robustness of Random Forest (RF), and the benefits of using stratified cross-validation and hyperprameter optimization to tackle data imbalance. Critically, for neuroscience ML applications that seek to minimize overall classification error, we recommend the routine use of BAcc, which in the specific case of balanced data is equivalent to using standard Acc, and readily extends to multi-class settings. Importantly, we present a list of recommendations for dealing with imbalanced data, as well as open-source code to allow the neuroscience community to replicate and extend our observations and explore alternative approaches to coping with imbalanced data.

neuroscience↗