Biology subjects

Owen, A. M.

Publications and source records attributed to Owen, A. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Closed-Loop Auditory Stimulation Reveals Differential Sleep Oscillatory Contributions to Memory in Healthy Older Adults

Sleep oscillations during non-rapid eye movement (NREM) sleep support memory consolidation but decline with age. Phase-locked auditory stimulation (PLAS) enhances slow-wave activity, yet its effects on distinct oscillatory components and memory in older adults remain unclear. Sixteen healthy older adults (60 years or older; mean age = 65.06 +/- 3.53 years) participated in a randomized, single-blind, sham-controlled crossover study. Participants completed two stimulation nights and two sham nights in a sleep laboratory. Changes in slow oscillations (0.5-1.25 Hz), frontal theta (4-8 Hz), centrofrontal slow spindles (12-14 Hz), and centroparietal fast spindles (14-16 Hz) were compared between stimulation and sham conditions. Declarative memory was assessed using a word-pair recall task that required overnight retention, and broader cognitive performance was evaluated using the Creyos cognitive assessment battery. PLAS enhanced sleep oscillatory activity without altering sleep architecture. Compared with sham, stimulation increased slow oscillation, frontal theta, centrofrontal slow spindle, and centroparietal fast spindle power across both stimulation nights. Although word-pair recall did not improve at the group level, individual differences in stimulation-induced increases in fast spindle power were positively associated with individual differences in overnight memory improvement. Closed-loop auditory stimulation enhances multiple NREM oscillations in healthy older adults while preserving sleep architecture. Moreover, stimulation-induced increases in fast spindle activity track individual differences in overnight memory improvement, suggesting fast spindles as a physiological marker of successful sleep-dependent memory consolidation and a potential target for sleep-based neuromodulation in aging.

neuroscience↗

bioRxiv2026

Neuroanatomical subtypes of Long COVID reveal distinct cognitive profiles alongside longitudinal brain changes

BackgroundLong COVID is characterized by persistent symptoms following SARS-CoV-2 infection, including cognitive deficits among its most disabling manifestations. However, their neurobiological basis is poorly understood. Previous neuroimaging studies reported structural brain alterations, but few have integrated cognitive assessment, network-based analyses, and longitudinal imaging to identify neurobiological subtypes. MethodsWe studied 42 individuals with persistent post-COVID cognitive symptoms and 14 matched healthy controls using cognitive assessment and structural MRI. Multilayer brain networks were constructed from regional morphometric measures, and hierarchical clustering identified patient subgroups. Cross-sectional and longitudinal comparisons of brain structure, cognition, and function were performed, with exploratory brain-behavior correlations over six months. ResultsClustering identified two subgroups with distinct structural patterns. Compared with controls, one subgroup showed reduced gray matter density in cerebellar lobules VIIIa/VIIIb and the putamen (p < 0.05, TFCE-corrected), whereas the other showed no significant alterations. Cognitive differences between clusters did not survive multiple-comparison correction; however, several measures showed medium-to-large effect sizes (d = 0.70-1.01), suggesting meaningful cognitive differences requiring confirmation in larger cohorts. Longitudinal analyses revealed increased medial frontal gray matter density (p < 0.05) associated with visuospatial/executive performance. ConclusionsThese exploratory findings suggest that post-COVID cognitive symptoms are associated with heterogeneous neurobiological profiles rather than a uniform pattern of impairment. Structural alterations involving cerebellar, striatal, and frontal regions may reflect distinct neuroanatomical phenotypes. Longitudinal findings suggest medial frontal structural reorganization with functional relevance. These findings support data-driven stratification for characterizing neurobiological heterogeneity in Long COVID and provide a foundation for future hypothesis-driven studies.

neuroscience↗

bioRxiv2026

The blueprint of human functional architecture shifts from cognition to anatomy during perturbations of consciousness

Consciousness and cognition arise from the ongoing interactions between brain regions. Synchronous fluctuations of fMRI signals may indicate that two brain regions perform similar cognitive functions, but neural interactions are also constrained by anatomical connectivity and regions molecular, cytoarchitectonic, and metabolic profiles. Here we disentangle the respective contributions of ongoing cognition and multimodal neurobiological constraints in shaping functional connectivity. We jointly contextualise haemodynamic FC against eight distinct multimodal representations of the human connectome: (i) structural connectivity from diffusion tractography; (ii) spatial embedding; (iii) similarity of transcriptional profiles from gene expression; (iv) similarity of receptor profiles from Positron Emission Tomography; (v) laminar profile similarity from histology; (vi) correlated electrophysiological activity from magnetoencephalography; (vii) correlated metabolic activity from PET glucose uptake; (viii) coordinated activation across 123 cognitive operations from the NeuroSynth meta-analytic engine. We demonstrate that cognitive co-activation is the dominant predictor of inter-regional fMRI synchrony in the awake human brain, even when quantified using intracranial electrical stimulation. Crucially, this predominance of cognitive co-activation for shaping functional connectivity is systematically obliterated across five datasets of pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anaesthesia with sevoflurane, propofol, or ketamine) when cognition is disconnected from the environment or altogether abolished. Altogether, we show that multimodal predictors of functional architecture shift away from cognitive co-activation and toward anatomicalmolecular constraints during pharmacological and pathological perturbations of consciousness.

neuroscience↗

bioRxiv2024

Diminished functional gradient of the precuneus during altered states of consciousness

The relationship between the default mode network (DMN) and task-positive networks, such as the frontoparietal control network (FPCN), is a prominent feature of functional connectivity (FC) in the human brain. This relationship is primarily anticorrelated at rest in healthy brains and is disrupted in altered states of consciousness. Although the DMN and FPCN seem to perform distinct and even opposing roles, they are anatomically adjacent and exhibit ambiguous boundaries. To test the hypothesis that the DMN-FPCN distinction manifests probabilistically rather than having absolute anatomical boundaries, we examined the differences in FC along the dorsal-ventral (d-v) axis in the posterior precuneus (PCu), which serves a convergence zone between the DMN and FPCN. Our findings indicate that the connectivity differences along this axis are continuous as characterized by linear slopes. Notably, these linear relationships (i.e., functional gradients of the precuneus/FGp) are present only within the territories of the DMN and FPCN, respectively associating with positive and negative slopes. Furthermore, the gradient is functionally relevant, as its spatial configurations change in specific ways in altered states of consciousness (ASC): the magnitude of FGp is similarly impaired across different types of ASC, while the spatial entropy of FGp differs between psychedelic and sedative states. These results suggest that the DMN and FPCN, while appearing distinct, may originate from a single, integrated mechanism. Significance StatementThis research provides new insights into the brains functional organization underlying human conscious states by examining the relationship between two large-scale networks: the default mode network (DMN) and the frontoparietal control network (FPCN). These networks, which are attuned to handle internal and external information respectively, are often viewed as oppositional. However, our findings indicate they form an integrated system with continuous connectivity. We identified the posterior precuneus as a key convergence point, revealing a gradient of connectivity between the two networks. This gradient flattens during altered states of consciousness induced by psychedelics or sedatives, showing a loss of functional differentiation between the DMN and FPCN.

neuroscience↗

bioRxiv2024

The neural correlates of shared and individual experience

Contemporary neuroscience research typically focuses on shared contents of experience and common neural states. Conversely, we set out to explore the neural correlates of individual- specific experiences that shape the distinct traits of each person. We propose an approach through which we compute individual-specific dynamics of functional connectivity states. These dynamics do not require estimation of common states across individuals and can be directly related to dynamic behavioural ratings of subjective experience. To this end, we leverage a unique functional magnetic resonance imaging dataset where subjects listened to an engaging naturalistic story while awake and under different levels of anaesthesia, altering or abolishing conscious experience. We find that this method can detect correspondences between neural and subjective dynamics. We then show that the dynamics of the default mode network underlie more personal experiences of the story as they are more dissimilar between participants during awareness compared to unconsciousness. On the other hand, the auditory and posterior dorsal attention networks show higher inter-subject similarity in consciousness compared to unconsciousness and suggest that the dynamics of these networks support more "generalisable" experiences of the story. We further characterise individual-specific brain dynamics by showing that they are associated with higher complexity in consciousness, whilst conversely, brain dynamics underlying shared experience become less complex during the conscious experience of the story.

neuroscience↗

bioRxiv2024

On the same wavelength: The relationship between neural synchrony and cognitive ability during movie watching in late childhood and early adolescence

Cognitive development in late childhood and adolescence occurs alongside increasingly complex environments. To examine how cognitive abilities relate to neural processing of naturalistic experiences, we analyzed fMRI data from 309 children and adolescents (ages 7-15; majority White) in the Healthy Brain Biobank. Participants watched a 10-minute clip of Despicable Me during scanning and completed the WISC. Intersubject correlation (ISC) was used to measure brain synchrony during viewing. Adolescents (11-15) with higher cognitive scores showed greater ISC in default mode and frontoparietal networks. In contrast, younger children (7-11) with high scores showed increased synchrony only in somatosensory regions. These findings suggest age- and cognition-related differences in how children and adolescents process complex, real-world stimuli.

neuroscience↗

bioRxiv2024

A thalamic perspective of (un)consciousness in pharmacological and pathological states in humans

Currently, there is substantial ongoing discussion around the functional role of the thalamus in consciousness. What is missing in the literature, however, is a systematic investigation of the relevance of specific thalamic nuclei in pharmacologically and pathologically altered states of consciousness in humans. Using functional neuroimaging in both healthy anaesthetised volunteers and patients with disorders of consciousness (DOC), we sought to identify which specific thalamic subregions in both cohorts may be differentially significant for loss of consciousness. Our findings revealed that the pulvinar (Pu) and ventral-latero-ventral (VLV) nuclei, in anaesthesia, and the VLV, in DOC, had distinct functional connectivity patterns related to the default mode and somatomotor networks. Remarkably, among all nuclei, the Pu was found to have the strongest functional connectivity change with anaesthetic-induced loss of consciousness, while in DOC patients, we found the VLV revealed the strongest connectivity change in comparison with healthy controls. Furthermore, we provide evidence that this neural connectivity biomarker in patients also mirrors the changes observed at the behavioural level, which could have clinical implications for targeted deep brain stimulation in therapy for DOC.

neuroscience↗

bioRxiv2023

Dynamical structure-function correlations provide robust and generalizable signatures of consciousness in humans

Resting-state functional magnetic resonance imaging evolves through a repertoire of functional connectivity patterns which might reflect ongoing cognition, as well as the contents of conscious awareness. We investigated whether the dynamic exploration of these states can provide robust and generalizable markers for the state of consciousness in human participants, across loss of consciousness induced by general anaesthesia or slow wave sleep. By clustering transient states of functional connectivity, we demonstrated that brain activity during unconsciousness is dominated by a recurrent pattern primarily mediated by structural connectivity and with a reduced capacity to transition to other patterns. Our results provide evidence supporting the pronounced differences between conscious and unconscious brain states in terms of whole-brain dynamics; in particular, the maintenance of rich brain dynamics measured by entropy is a critical aspect of conscious awareness. Collectively, our results may have significant implications for our understanding of consciousness and the neural basis of human awareness, as well as for the discovery of robust signatures of consciousness that are generalizable among different brain conditions.

neuroscience↗

bioRxiv2023

Converging on consistent functional connectomics

Functional interactions between brain regions can be viewed as a network, empowering neuroscientists to leverage network science to investigate distributed brain function. However, obtaining a brain network from functional neuroimaging data involves multiple steps of data manipulation, which can drastically affect the organisation and validity of the estimated brain network and its properties. Here, we provide a systematic evaluation of 576 unique data-processing pipelines for functional connectomics from resting-state functional MRI, obtained from all possible recombinations of popular choices for brain atlas type and size, connectivity definition and selection, and global signal regression. We use the portrait divergence, an information-theoretic measure of differences in network topology across scales, to quantify the influence of analytic choices on the overall organisation of the derived functional connectome. We evaluate each pipeline across an entire battery of criteria, seeking pipelines that (i) minimise spurious test-retest discrepancies of network topology, while simultaneously (ii) mitigating motion confounds, and being sensitive to both (iii) inter-subject differences and (iv) experimental effects of interest, as demonstrated by propofol-induced general anaesthesia. Our findings reveal vast and systematic variability across pipelines suitability for functional connectomics. Choice of the wrong data-processing pipeline can lead to results that are not only misleading, but systematically so, distorting the functional connectome more drastically than the passage of several months. We also found that the majority of pipelines failed to meet at least one of our criteria. However, we identified 8 candidates satisfying all criteria across each of four independent datasets spanning minutes, weeks, and months, ensuring the generalisability of our recommendations. Our results also generalise to alternative acquisition parameters and preprocessing and denoising choices. By providing the community with a full breakdown of each pipelines performance across this multi-dataset, multi-criteria, multi-scale and multi-step approach, we establish a comprehensive set of benchmarks to inform future best practices in functional connectomics.

neuroscience↗

bioRxiv2023

Improved short-channel regression for mapping resting-state functional connectivity networks using functional near-infrared spectroscopy

Resting-state functional connectivity (rsFC) is an attractive biomarker of brain function that can vary with brain injury. The simplicity of resting-state protocols coupled with the main features of functional near-infrared spectroscopy (fNIRS), such as portability and versatility, can facilitate the monitoring of unresponsive patients in acute settings at the bedside. However, accurately mapping rsFC networks is challenging due to signal contamination from non-neural components, such as scalp hemodynamics and systemic physiology. Physiological noise may be mitigated through the use of short channels which may be able to provide sufficient information to eliminate the need for additional measurement devices, decreasing the complexity of the experimental setup. To this end, we examined the extent to which systemic physiology is embedded in the short-channel data and improved short-channel regression to account for temporal heterogeneity in the scalp hemodynamics. Our findings indicate that using temporal shifts in the short-channel data increases the agreement, by 70% on average, between short-channel regression and regression that includes short channels and physiological recordings. Overall, this method decreases the need for additional physiological recordings when mapping rsFC networks, providing a viable alternative when such measurements are not available or feasible.

neuroscience↗

bioRxiv2023

Differential effects of prolonged aerobic and resistance exercise on cognitive functioning in sedentary young adults

ObjectivesInconsistencies in the literature make it difficult to outline the relationship between exercise and cognition in young adults. Our aim is to better understand the relationship between prolonged aerobic and resistance exercise and cognitive abilities in sedentary young adults, and how this relationship is mediated by changes in cardiovascular fitness. MethodsTwenty-three volunteers were recruited and assigned to two groups to complete one hour of continuous daily workout sessions of aerobic (SPIN) and anaerobic (SCSW) exercises over a 30 day period. Each subject was provided with a Polar-10 wearable to record the heart rate (HR) activity during the workout sessions. The workout sessions were completed during five consecutive days over four consecutive weeks. Each week, HR data were collected from the last workout session. Volunteers also completed a neurocognitive test battery (Cambridge Brain Sciences, CBS) each exercise session, including an additional baseline measure before exercise regime began. ResultsWe found that memory, reasoning and verbal abilities improved throughout the aerobic, but not the resistance exercise program. We found a positive correlation between heart rate index (HRI) and memory and reasoning test scores. We also found a negative correlation between reasoning ability and HRM (heart rate mean), and heart rate skewness (SKW). The results of a regression model to predict memory and reasoning abiltiies revealed that memory was best predicted by HRI and HRM, while the reasoning ability was best predicted by only HRI. ConclusionRegular aerobic exercises improved specific cognitive performance and it was possible to predict the performance by employing the HR parameters HRI and HRM.

neuroscience↗

bioRxiv2022

Processing of the same narrative stimuli elicits common functional connectivity dynamics between individuals

It has been suggested that the richness of conscious experience can be directly linked to the richness of brain state repertories. Brain states change depending on our environment and activities we engage in by taking both external and internally derived information into account. It has been shown that high-level sensory stimulation changes local brain activity and induces neural synchrony across participants. However, the dynamic interplay of cognitive processes that underlie moment-to-moment information processing remains poorly understood. Using naturalistic movies as an ecological laboratory model of the real world, here we assess how the processing of complex naturalistic stimuli alters the dynamics of brain networks interactions, and how these in turn support information processing. Participants underwent fMRI recordings during movie watching, scrambled movie watching, and rest. Measuring phase-synchrony between different brain networks, we computed whole-brain connectivity patterns. We showed that specific connectivity patterns were associated with each experimental condition. We found a higher synchronization of brain patterns across participants during movie watching compared to resting state and scrambled movie conditions. Moreover, synchronization increased during the most engaging parts of the movie. The synchronization dynamics across participants were associated with suspense; more suspenseful scenes induced higher synchronization. These results suggest that processing of the same high-level information elicits common neural dynamics among individuals and that whole-brain functional connectivity tracks variations in the processed information and the subjective experience.

neuroscience↗

bioRxiv2022

MyD88-Dependent Signaling Drives Toll-Like Receptor-Induced Trained Immunity in Macrophages

Immunocompromised populations are highly vulnerable to developing life-threatening infections. Strategies to protect patients with weak immune responses are urgently needed. Employing trained immunity, whereby innate leukocytes undergo reprogramming upon exposure to a microbial product and respond more robustly to subsequent infection, is a promising approach. Previously, we demonstrated that the TLR4 agonist monophosphoryl lipid A (MPLA) induces trained immunity and confers broad resistance to infection. TLR4 signals through both MyD88- and TRIF-dependent cascades, but the relative contribution of each pathway to induction of trained immunity is unknown. Here, we show that MPLA-induced resistance to Staphylococcus aureus infection is lost in MyD88-KO, but not TRIF-KO, mice. The MyD88-activating agonist CpG (TLR9 agonist), but not TRIF-activating Poly I:C (TLR3 agonist), protects against infection in a macrophage-dependent manner. MPLA- and CpG-induced augmentation of macrophage metabolism and antimicrobial functions is blunted in MyD88-, but not TRIF-KO, macrophages. Augmentation of antimicrobial functions occurs in parallel to metabolic reprogramming and is dependent, in part, on mTOR activation. Splenic macrophages from CpG-treated mice confirmed that TLR/MyD88-induced reprogramming occurs in vivo. TLR/MyD88-triggered metabolic and functional reprogramming was reproduced in human monocyte-derived macrophages. These data show that MyD88-dependent signaling is critical in TLR-mediated trained immunity.

immunology↗

bioRxiv2022

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brains functional architecture.

neuroscience↗

bioRxiv2022

Aperiodic brain activity and response to anesthesia vary in disorders of consciousness

The analysis of human EEG has traditionally focused on oscillatory power, which is characterized by peaks above an aperiodic component in the power spectral density. This study investigates the aperiodic EEG component of individuals in a disorder of consciousness (DOC); how it changes in response to exposure to anesthesia; and how it relates to the brains information richness and criticality. High-density EEG was recorded from 43 individuals in a DOC, with 16 of these individuals undergoing a protocol of propofol anesthesia. The aperiodic component was defined by the spectral slope of the power spectral density. Our results demonstrate that the EEG aperiodic component is more informative about the participants level of consciousness than the oscillatory component. Importantly, the pharmacologically induced change in the spectral slope from 30-45 Hz positively correlated with individuals pre-anesthetic level of consciousness. The pharmacologically induced loss of information-richness and criticality was associated with individuals pre-anesthetic aperiodic component. During exposure to anesthesia, the aperiodic component was correlated with 3-month recovery status for individuals with DOC. The aperiodic EEG component has been historically neglected; this research highlights the necessity of considering this measure for the assessment of individuals in DOC and future research that seeks to understand the neurophysiological underpinnings of consciousness.

neuroscience↗

bioRxiv2021

Network dynamics scale with levels of awareness

Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of brain dynamics pertaining to small world topology (quantified by sample entropy; dSW-E) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.

neuroscience↗

bioRxiv2021

Paths to Oblivion: Common Neural Mechanisms of Anaesthesia and Disorders of Consciousness

The human brain generates a rich repertoire of spatiotemporal dynamics during normal wakefulness, supporting a wide variety of conscious experiences and cognitive functions. However, neural dynamics are reconfigured, in comparable ways, when consciousness is lost either due to anaesthesia or disorders of consciousness (DOC). Here, leveraging a neurobiologically realistic whole-brain computational model informed by functional MRI, diffusion MRI, and PET, we sought to identify the neurobiological mechanisms that explain the common reconfiguration of neural dynamics observed both for transient pharmacological intervention and chronic neuroanatomical injury. Our results show that, by incorporating local inhibitory action through a PET-based GABA receptor density map, our model can reproduce the brain dynamics of subjects undergoing propofol anaesthesia, and that this effect depends specifically on the spatial distribution of GABA receptors across cortical regions. Additionally, using a structural connectome obtained from DOC patients, we demonstrate how the dynamics that characterise loss of consciousness can emerge from changes in neuroanatomical connectivity. Crucially, we find that each of these two interventions generalises across datasets: a model with increased GABA-mediated inhibition can reproduce the dynamics of DOC patients brains, and a model with a DOC connectome is also compatible with brain dynamics observed during propofol anaesthesia. These results demonstrate how increased inhibition and connectome randomisation represent different neurobiological paths towards the characteristic dynamics of the unconscious brain. Overall, the present findings begin to disentangle the neurobiological mechanisms by which highly dissimilar perturbations of the brains neurodynamics can lead to unconsciousness.

neuroscience↗

bioRxiv2020

A Synergistic Workspace for Human Consciousness Revealed by Integrated Information Decomposition

A central goal of neuroscience is to understand how the brain orchestrates information from multiple input streams into a unified conscious experience. Here, we address two fundamental questions: how is the human information-processing architecture functionally organised, and how does its organisation support consciousness? We combine network science and a rigorous information-theoretic notion of synergy to delineate a "synergistic global workspace", comprising gateway regions that gather synergistic information from specialised modules across the brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the brains default mode network, whereas broadcasters coincide with the executive control network. Demonstrating the empirical relevance of our proposed architecture for neural information processing, we show that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to a diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory. Taken together, this work provides a new perspective on the role of prominent resting-state networks within the human information-processing architecture, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

neuroscience↗