Biology subjects

Kringelbach, M. L.

Publications and source records attributed to Kringelbach, M. L..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Beyond where: When and how brain stimulation drives state transitions

Brain stimulation is increasingly used to treat neurological and psychiatric conditions, but stimulation sites and timing are typically chosen based on a priori assumptions from prior studies, not individualised mechanisms. Here, we investigate why some brain regions respond more to stimulation, when they respond best, and whether optimal targets for brain-state transitions are defined by functional anatomy (e.g. an auditory region in a resting-to-listening task transition), by system dynamics, or a combination of both. To do so, we build subject-specific whole-brain Hopf models fitted to MEG data, separating signals into five canonical frequency bands. We find that regions with a smaller oscillation radius and greater temporal variability respond more strongly to stimulation. Moreover, responsiveness was highly dependent on state and frequency band, with slower frequencies exhibiting phase-driven responsiveness, while faster ones depending more on network synchrony. Importantly, optimal nodes for transitioning between brain states are not defined by functional labels but rather by their dynamical regime. These results emphasise the value of mechanistic, personalised models for identifying when and where to stimulate the brain, and may help inform more precise brain-stimulation strategies.

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bioRxiv2026

Functional connectome harmonics and dynamic connectivity maps of the preadolescent brain

The maturation of large-scale functional brain networks during preadolescence underpins critical cognitive and behavioral development. However, the spatial and temporal organization of these networks in this age group remains incompletely characterized. Here we applied Functional Connectome Harmonics (FCH) and Leading Eigenvector Dynamics Analysis (LEiDA) to resting-state fMRI data from over 11,000 children aged 9-10 years in the ABCD Study. FCH revealed hierarchical spatial gradients spanning cortical and subcortical regions, while LEiDA identified recurrent dynamic brain states aligned with canonical intrinsic connectivity networks. Linking these spatial and temporal components, we established a low-dimensional harmonic scaffold constraining brain dynamics during this developmental window. These findings provide a large-scale spatiotemporal reference framework of preadolescent functional brain organization, offering a foundation for characterizing neurodevelopmental benchmarks and early neural markers relevant to adolescent mental health.

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bioRxiv2025

Thermodynamics of consciousness: A non-invasive perturbational framework

The quest for reliable and objective measures of consciousness is critical in basic and clinical neuroscience. Across species, the Perturbational Complexity Index (PCI) has emerged as a robust empirical marker by directly perturbing the brain, yet its underlying principles of physics are not fully understood. Here, we bridge this gap by introducing a non-invasive framework based on generative whole-brain models of non-equilibrium brain dynamics. Using these models, we identified violations of the Fluctuation-Dissipation Theorem (FDT) in humans and rodents across wakefulness, anesthesia, and disorders of consciousness. Mirroring the patterns observed with PCI, we found decreased FDT violations in unresponsive disorders of consciousness and anesthesia compared to conscious conditions. This reveals a close link between PCI and non-equilibrium dynamics in spontaneous brain signals, grounding PCI in fundamental principles of physics. Overall, this framework offers new complementary, non-invasive, model-based avenues for understanding the nature of consciousness and for developing objective tools to assess its loss and recovery in health and disease. It also provides a principled foundation for discovering novel strategies to restore consciousness.

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bioRxiv2025

Modeling Hierarchical Brain Dynamics Outperforms Hormonal Biomarkers in Predicting Menstrual Cycle Phases

Hormonal fluctuations across the menstrual cycle influence large-scale brain dynamics, yet the underlying neurobiological mechanisms remain poorly understood. In this study, 60 nat-urally cycling women were scanned using resting-state fMRI during the early follicular, pre-ovulatory, and mid-luteal phases. We then applied a thermodynamics-inspired framework to explore the functional hierarchical organization of whole-brain dynamics across these phases. First, we found that brain dynamics are significantly modulated by estradiol, progesterone, and age across multiple resting-state networks. Second, to elucidate underlying mechanisms, we es-timated generative effective connectivity (GEC) matrices using whole-brain models and trained support vector machine classifiers to predict menstrual phases. These model-based biomarkers outperformed traditional functional connectivity and hormone measures in classifying men-strual cycle phases. These findings reveal that menstrual cycle-related changes modulate the hierarchical reorganization of brain dynamics, highlighting the potential of model-based ap-proaches to advance womens brain health research.

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bioRxiv2025

The Turbulent Brain: a toolbox to compute the turbulent dynamical behaviour of whole-brain activity

Brain disorders remain one of the greatest challenges in neuroscience. Computational precision medicine offers a promising framework to reveal the mechanistic principles governing both healthy and pathological brain dynamics. In this context, we present The Turbulent Brain (TTB) toolbox, an open-source MATLAB platform that implements and disseminates the turbulence framework for immediate and widespread application in neuroscience research. The toolbox combines model-free and model-based analyses through an intuitive graphical interface, enabling customizable workflows across different parcellations and preprocessing pipelines. Our toolbox builds on recent advances demonstrating that turbulence physics can effectively capture the complex spatiotemporal dynamics of brain activity as a high-dimensional system operating far from equilibrium. This framework allows researchers to explore how fundamental mechanisms are modulated across distinct brain states and neurological and psychiatric disorders, including disorders of consciousness and major depressive disorder. As an illustrative application case, we used TTB to analyse fMRI data from 176 individuals from the Human Connectome Project during resting state and movie watching, showing that movie watching, as compared to resting state, significantly reduces information transmission in terms of turbulence measures, with stronger reductions observed during Creative Commons movie watching compared to Hollywood movies. In summary, the TTB toolbox establishes an accessible framework providing a methodological bridge between nonlinear physics and computational neuroscience, offering new tools for investigating psychiatric conditions and altered states of consciousness.

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bioRxiv2025

Restoring signatures of consciousness by thalamic stimulation in a whole-brain model of an anesthetized nonhuman primate

Treatment options for Disorders of Consciousness (DoC) are limited due to insufficient understanding of the underlying neurobiological mechanisms. Two primary strategies for characterizing DoC and assessing treatment efficacy are in vivo experiments with animal models, and in silico computational models. We combined both approaches by creating a whole-brain model tailored to the experimental functional magnetic resonance imaging (fMRI) data of a single anesthetized macaque. It was previously reported in an in vivo experiment that anesthesia-induced loss of consciousness was partially reversed by specific electrical stimulation of the thalamic central nuclei. The in silico model reproduced the brain dynamics underlying the restoration of consciousness, providing a potential explanation for the transition between these brain states as continuous trajectories unfolding in a low-dimensional space. Our results demonstrate that whole-brain computational models reproduce the spatiotemporal properties of fMRI recordings during loss of consciousness and during its recovery induced by electrical stimulation, enabling computational exploration of perturbation-based interventions to potentially personalize treatment and aid recovery of consciousness in DoC patients.

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bioRxiv2025

Disrupted hierarchical organization in disorders of consciousness revealed by fluctuation-dissipation deviations

Evaluating consciousness levels after coma remains clinically challenging, and probing the brains functional hierarchy offers model-based biomarkers of brain states. We characterize the hierarchy loss in disorders of consciousness (DoC) via departures from non-equilibrium dynamics. Irreversible, directed interactions are indexed by deviation from the fluctuation- dissipation theorem (FDT), computed from individualized whole-brain models fit to fMRI from controls and patients in minimally conscious state (MCS) or unresponsive wakefulness syndrome (UWS). Global and resting-state network dynamics in DoC were closer to equilibrium than in controls, decreasing stepwise with decreasing levels of consciousness. Mapping site-specific hierarchical drive over the system revealed disruptions within default-mode network components (e.g., medial and dorsolateral superior frontal gyrus) and subcortical hubs (e.g., thalamus, pallidum and putamen) differentiating between all groups. Recovery of near-control hierarchy in the visual network differentiated MCS from UWS, whereas multiple limbic areas showed similar abnormalities across both DoC groups. Together, these results identify non-equilibrium dynamics as a signature of conscious capacity and stablish FDT deviation as a principled, model-based hierarchy measure that can be operationalised for clinical stratification and monitoring, opening avenues for targeted in silico intervention planing.

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bioRxiv2025

Quantum-like dynamics in the human brain

Emerging new research indicates evidence of quantum-like (QL) probability laws, including interference effects, in non-quantum physical systems using coupled oscillators. This can produce QL states which can compute in a QL fashion. Given the success of using coupled oscillators for human whole-brain modelling, we investigate the possibility of QL dynamics in the human brain. Here, we investigate how the special topology of human brain anatomy together with QL bits can promote the rich dynamic repertoire necessary for human advanced cognition. We systematically changed the level of QL processing in a whole-brain model. We found the QL regime provided the best whole-brain model fit to large-scale human empirical neuroimaging data. Extraordinarily, at this optimum point we found significantly lower energy consumption than for the non-QL networks. Mechanistically, this implies that the significantly larger whole-brain spectral gap for QL networks offers a backbone to the functional metastability needed to provide the necessary dynamical regime for efficient computation. The underlying QL spectral gaps amplify through interference the metastability and richness of repertoire of the human brain. Overall, we found that the special topology of the human brain promotes QL information processing.

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bioRxiv2025

The turbulent brain: Modelling vortex interactions for understanding human cognition

The human brain needs distributed, time-critical computation to efficiently solve complex problems. Turbulence provides such highly efficient spacetime information processing and transmission across wide-spread brain networks, yet we have been missing a mechanistic understanding of the interactions of turbulent vortices underlying human cognition. Here, we build the first whole-brain model of turbulent vortices as defined by the levels of local synchronisation in brain signals quantifying turbulent interactions in vortex space. Specifically, using large-scale human neuroimaging data, we found that the interactions of turbulent vortices is an excellent framework for understanding cognition and brain computation. It is not only useful for distinguishing the detailed spacetime dynamics of rest and cognition - but can even distinguish between subtle sub-components of cognitive tasks, where manipulation of vortices can be shown to change cognition. Overall, this whole-brain framework creates a natural vortex space for the brain computation underlying cognition, as well as potentially providing novel ways of controlling turbulent interactions in disease.

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bioRxiv2025

Physical exercise and brain network dynamics: reduction of frontoparietal-striatal connectivity following 1 hour of aerobic cycling

Physical exercise is beneficial for metabolic health and cognitive performance. In addition, exercise can be highly pleasurable and and serves as an effective stress reliever. Extant studies have highlighted frontal, parietal, and subcortical brain changes following acute bouts of exercise. However, slower, slightly delayed brain correlates after exercise at the network level have not been studied. Therefore, this studys objective was to investigate the changes in dynamic functional connectivity after 60 minutes of exercise in healthy males. Here we measured a 6-minute resting state fMRI in 24 young males at baseline and after a 60-minute cycling exercise challenge. Apart from routine preprocessing, the data were denoised with FSL-FIX and modeled with i) leading eigenvector dynamics analysis (LEiDA) to probe whole brain network dynamics and ii) with group independent component analysis (ICA) and dual regression to quantify static brain connectivity. The within subject statistical tests compared baseline to post-exercise conditions. We found that a striato-fronto-parietal network is destabilized after exercise, as indicated by a lower probability of occurrence in dynamic analysis through LEiDA. The brain areas in the network include the bilateral caudate, putamen and pallidum as well as middle orbitofrontal, frontal operculum, frontal trigonum and inferior parietal cortices. No differences between baseline and post exercise conditions were found in the dual regression of the group ICA components. We conclude that 60 minutes of cycling causes a prolonged effect in brain network dynamics, reducing synchronization between the striatum and frontoparietal networks with respect to baseline. This provides insights into the network-level neural correlates of aerobic exercise, which may be directly linked with the stress relieving effects of physical exercise.

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bioRxiv2025

Inception: Simulating Personalized Long-Term Recovery in Disorders of Consciousness using Whole-Brain Computational Perturbations

Advancements in the treatment of Disorders of Consciousness have seen significant progress with per-turbative techniques and pharmacological therapies. Despite their potential, the underlying mechanisms of their variable efficacy remain poorly understood. To address this challenge, recent studies have utilised whole-brain modelling to simulate in silico perturbations. However, existing models focus exclusively on system behaviour during active stimulations, leaving unexplored how the brain dynamics evolve in post-acute and long-term stages, crucial in the recovery of consciousness. Here, we introduce Inception, a novel personalized approach to in silico perturbation modelling. We use a whole-brain models to simulate the perturbations and to unravel information about the long term effects of the proposed intervention. Applied to fMRI data from patients in a minimally conscious state and an unresponsive wakefulness state, our approach effectively simulates the transition to a healthy state, generating perturbed data closely resembling healthy brain activity. Moreover, we show that Inception enhances patient classification through machine learning, outperforming functional connectivity-based approaches. Finally, we investigate the correlation between perturbation responses and brain neuroreceptors, proposing that Inception might capture the long-term effects of pharmacological interventions in Disorders of Consciousness treatment.

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bioRxiv2025

Shared and modality-specific brain networks underlying predictive coding of temporal sequences

Predictive coding posits that the brain continuously generates and updates internal models to anticipate incoming sensory input. While auditory and visual modalities have been studied independently in this context, direct comparisons using matched paradigms are scarce. Here, we employed magnetoencephalography (MEG) to investigate how the brain of 83 participants encodes and consciously recognises temporally unfolding sequences that acquire Gestalt-like structure over time, a feature rarely addressed in cross-modal research. Participants memorised matched auditory and visual sequences with coherent temporal structure and later identified whether test sequences were familiar or novel. Multivariate decoding revealed robust discrimination between the brain mechanisms underlying encoding and recognition of memorised and novel sequences, with sustained temporal generalisation in the auditory domain and time-specific responses in the visual domain. Using the BROAD-NESS pipeline, we identified modality-specific and supramodal brain networks. Auditory memory engaged auditory cortex, cingulate gyrus, and hippocampus, whereas visual memory involved orbitofrontal cortex and visual areas. Notably, both modalities recruited a shared network including hippocampus and medial cingulate during recognition. These findings provide compelling evidence for distinct and shared predictive learning mechanisms across sensory systems, advancing our understanding of how the brain integrates and evaluates temporally structured, Gestalt-like information.

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bioRxiv2025

FREQ-NESS reveals age-related differences in frequency-resolved brain networks during auditory recognition and resting state

Understanding how brain networks operate across different frequencies during cognitive tasks, and how these dynamics change with age, remains a central challenge in cognitive neuroscience. While previous studies have focused on resting-state activity and passive listening, less is known about frequency-specific brain dynamics during event-related tasks that require active memory engagement. In this study, we extend the recently developed FREQ-NESS analytical pipeline by adapting it to event-related task and resting state source-reconstructed magnetoencephalography (MEG) data from 70 healthy participants. This method quantified the variance explained by frequency-specific brain networks, their spatial organization, and associated time-resolved power estimates. We found significant effects of age, condition, and their interaction in the variance explained by leading components at 1.07 Hz, 2.86 Hz, and 10.00 Hz. Younger adults exhibited stronger peaks at 1.07 and 2.86 Hz during the task and a more pronounced 10.00 Hz peak at rest, whereas older adults showed the opposite pattern. Time-frequency analysis revealed age- and condition-dependent desynchronization in the alpha and beta bands (7.10-22.90 Hz). These findings demonstrate the effectiveness of the adapted FREQ-NESS pipeline for event-related tasks and highlight the importance of frequency-resolved network analysis for characterizing age-related changes in active auditory memory processing.

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bioRxiv2025

The synergistic interactions of low-dimensional brain modes

Neuroimaging techniques produce vast amounts of data, capturing brain activity in a high-dimensional space. However, brain dynamics are consistently shown to reside in a rather lower-dimensional space, which contains relevant information for cognition and behavior. This dimensionality reduction reflects distinct types of interactions between brain regions, such as redundancy -shared neural information distributed across regions- and synergy, where information emerges only when regions are considered collectively. Significant efforts have been devoted to developing linear and non-linear algorithms to reveal these low-dimensional dynamics, often termed "brain modes." Here, we apply various dimensionality reduction techniques to resting-state functional magnetic resonance imaging (fMRI) data from 100 healthy participants to examine how synergistic interactions in brain dynamics are preserved by these techniques. We first demonstrate that biologically informed brain parcellation modulates and preserves synergy-dominated interactions. Next, we show that synergy among low-dimensional modes enhances functional-connectivity reconstruction: nonlinear autoencoders not only achieve the lowest reconstruction error but also maximally preserve synergy, outperforming principal component analysis, diffusion maps, and Laplacian eigenmodes. Finally, we confirm previous results suggesting that global signal regression helps to identify synergistic interactions between regions. Our findings establish synergy preservation as a complementary criterion to reconstruction accuracy, highlighting autoencoders as a nonlinear tool for uncovering synergistic low-dimensional brain modes from high-dimensional neuroimaging data.

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bioRxiv2025

The cost of cognition: Measuring the energy consumption of non-equilibrium computation

In biological systems, survival is predicated on an animal being able to perform computations quickly on a minimal energy budget. What is the energy consumption of non-equilibrium brain computation, i.e., what is the cost of cognition? Previous literature has estimated the metabolic cost using neuroimaging measures of glucose consumption but complementary to these findings, here we directly estimate the computational costs by combining the new field of stochastic thermodynamics with whole-brain modelling. We developed the COCO (COst of COgnition) framework using an analytical expression quantifying the links between energy cost, non-equilibrium and information processing for any given brain state measured with neuroimaging. Importantly, this key relationship also holds at the level of individual brain regions. We used this to quantify the benefits of information processing on the highly anatomically, interconnected hierarchical systems of the brain. Crucially, in empirical neuroimaging data we demonstrate that the human brain uses significantly less energy overall than other mammals (including non-human primates and mice), suggestive of an evolutionary optimisation of the effectiveness of computation. Focusing on the cost of cognition, using large-scale human neuroimaging data of 970 healthy human participants, we show that the resting state uses significantly less energy that seven different cognitive tasks. Furthermore, different kinds of tasks require different amounts of non-equilibrium, information processing and energy consumption. We found that tasks requiring more distributed computation also use more energy. Overall, these results directly quantify the cost of cognition, i.e., the non-equilibrium and energetic demands of information processing, allowing a deeper understanding of how the brain compute in a way that is far more energy efficient than current generations of digital computers and artificial intelligence.

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bioRxiv2025

Evolution's boldest trick: Neurotransmission modulated whole-brain computation captures full task repertoire

The perhaps most important unsolved problem in neuroscience is how the brain survives in a complex world by performing a rich repertoire of computation on a minimal energy budget. The brain is much better at adapting to the multiplicity of stimuli and outcomes than current generations of computers, artificial neural deep learning and reservoir model architectures. Yet, at first glance the brain appears to use a fixed anatomical architecture to perform the necessary huge variety of computations. But evolutions boldest trick is that in fact the brains effective connectivity is constantly being updated through neuromodulation to allow the rich repertoire of computation. Inspired by this, we created a whole-brain model using empirical neurotransmitter maps modulating the underlying local regional dynamics. This NEMO (neurotransmission modulated) whole-brain model is able to flexibly compute the full task repertoire and associated functional connectivity of the neuroimaging data from 971 healthy participants. For each individual we defined a measure of brain computability as the fitting of the NEMO whole-brain model to all tasks performed by the individual. Importantly, brain computability correlates with both behavioural performance on individual tasks and with a general behavioural measure of intelligence. Overall, our proposed unifying NEMO framework offers a natural way to sculpt different brain dynamics in a fixed brain architecture to compute the rich repertoire of tasks required for surviving and thriving.

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bioRxiv2025

An engine for systematic discovery of cause-effect relationships between brain structure and function

Characterising how perturbations of brain architecture influence brain function is essential to understand the origins of brain dysfunction, and devise potential avenues of treatment. Here we introduce a computational engine for systematic causal discovery of the functional consequences of altering network architecture and local biophysics in the brain. We integrate multimodal anatomical and functional neuroimaging to implement over 2, 000 in-silico brains, and provide mechanistic insight into the functional consequences of local lesions, global wiring, and empirically-derived maps of regional cytoarchitecture and chemoarchitecture. We comprehensively assess how each manipulation of brain macrostructure reshapes spatial and temporal signal coordination, information dynamics, and functional hierarchy--as well as spontaneous co-activation of meta-analytic cognitive circuits, and > 6, 000 dimensions of local neural dynamics. Our computational model systematically identifies which features of brain architecture have overlapping or antagonistic causal influence over each dimension of brain function, and how functional properties are traded off against each other across disorders and neuromodulation. We find that regions functional vulnerability to lesions in silico recapitulates their vulnerability to neurodevelopmental and psychiatric in vivo, along a core-periphery organisation. We provide convergent evidence that the brains wiring diagram is finely tuned to favour the hierarchical integration of information. Notably, our model successfully recapitulates known empirical results that have not been modelled before, including desynchronisation and flattening of the brains functional hierarchy induced by psychedelic 5HT2A agonists. To catalyse future discoveries, we make this resource freely available to the neuroscience community through an interactive website (https://systematic-causal-mapping.up.railway.app/), where users can interrogate our systematic database of simulated cause-effect relationships. Altogether, we provide a powerful computational engine to predict the functional consequences of experimental or clinical interventions, and drive neuroscientific hypothesis-generation.

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bioRxiv2025

LSD reconfigures the frequency-specific network landscape of the human brain

Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed FREQ-NESS method to MEG data from 14 healthy participants who received LSD under four conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. LSD significantly restructures canonical networks in the alpha and beta bands. Relative to broadband brain activity, it enhances the prominence of high alpha (12.1, 13.3 Hz) across all experimental conditions and high beta (25.3 Hz) in three conditions. Conversely, LSD decreases the prominence of low beta (18.1, 19.3 Hz) in both Open and Closed conditions and low alpha (8.5 Hz) in the latter. In addition, LSD substantially alters the spatial distributions or topographies of the networks. Under LSD, the low alpha (8.5 Hz) network shifts anteriorly toward the motor cortex, while high alpha (12.1, 13.3 Hz) becomes more localized to the visual cortex. Low beta (18.1, 19.3 Hz) expands over the temporal and occipital cortices, whereas high beta (25.3, 26.5 Hz) topographies remain unchanged. Our findings provide critical insights into the specific frequencies and spatial networks in which LSD modulates brain connectivity, adding nuance to prevailing theories about network disintegration under psychedelics. Significance statementPsychedelic substances such as lysergic acid diethylamide (LSD) profoundly alter perception and cognition, yet their effect on brain activity across different frequency bands remains unclear. Using FREQ-NESS applied to MEG data, we show that LSD reorganizes brain networks by enhancing high-frequency alpha and beta rhythms while suppressing lower-frequency counterparts. These changes occur across various experimental conditions and shift the spatial distribution of brain activity, particularly in motor and visual regions. Our findings suggest that LSD modulates brain connectivity in a frequency- and region-specific manner, offering new insights into how psychedelics alter consciousness. This work advances our understanding of LSDs neural effects, which may be relevant for therapeutic applications and models of brain function.

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