Biology subjects

Deco, G.

Publications and source records attributed to Deco, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Diminished ascending drive in transdiagnostic anhedonia shifts the cortico-subcortical hierarchy away from bottom-up dominance

Anhedonia, the diminished capacity to experience or pursue pleasure, is a core feature of mood and psychotic disorders, yet the large-scale brain dynamics underlying it remain uncharacterized. Dominant accounts posit striatal hypofunction with compensatory prefrontal over-recruitment, but they rest on activation magnitudes and symmetric correlations, which cannot resolve the direction of influence. Here, in 210 adults from the Transdiagnostic Connectome Project, we defined symptom-derived low- and high-anhedonia subgroups and estimated each participant's directed effective connectivity using a whole-brain generative model fitted to resting-state fMRI. In high anhedonia, the cortex shifted upstream relative to the subcortex, flattening the cortico-subcortical hierarchy. Correspondingly, the net balance of direct cortico-subcortical flow shifted from bottom-up to balanced. This shift recurred within the frontostriatal reward circuit and replicated across independent halves of each participant's data. Flow asymmetry also increased with subject-level severity. Decomposing flow into ascending and descending arms showed that both weakened in high anhedonia, but ascending subcortex-to-cortex and striatum-to-prefrontal drive fell more than the descending drive. These findings identify a reorganization of cortico-subcortical hierarchy in anhedonia and suggest that the previously reported prefrontal over-recruitment reflects diminished ascending drive rather than stronger cortical output.

neuroscience↗

bioRxiv2026

Serotonergic psychedelics delay resting state neurovascular coupling dynamics

Psychedelics are increasingly explored as tools to investigate consciousness and cognition, and as potential treatments for mood disorders. While neuroimaging has been central to characterizing their mechanisms of action, the interpretation of these studies may be confounded by the neurovascular effects elicited by these drugs. Here, we investigated the modulation of resting state neurovascular coupling by the serotonergic psychedelics LSD and DMT. Applying a blind deconvolution algorithm to blood-oxygen-level-dependent (BOLD) signals, we found that both drugs increased the estimated hemodynamic delays in regions overlapping with the distribution of serotonin receptors implicated in psychedelic action and vascular regulation. Deconvolution enhanced the detection of psychedelic-induced changes in whole-brain functional connectivity, suggesting that vascular effects obscure connectivity changes instead of generating spurious results. Finally, a biophysical whole-brain model linked these effects to increased flow-dependent feedback and slower dissipation of the vasoactive drive. These findings underscore the need to account for vascular effects in future psychedelic neuroimaging studies.

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bioRxiv2026

Whole-brain receptor markers and hub excitabilities determine acute and long-term outcomes in stroke

Following a stroke, changes in receptor systems have been observed that may influence the excitability of affected brain regions and drive recovery trajectories. Translating results from animal studies to patients remains a major challenge, and while imaging modalities have provided a wealth of findings, a mechanistic link between local receptor systems and observed imaging data is still missing. To bridge this gap, we built patient-specific digital twins with their own neuromodulatory profiles: we integrated 19 receptor and transporter density maps into a mechanistic whole-brain model, and estimated their influence on cortical excitability for each stroke patient and how these systems subsequently explain recovery trajectories. We found that distinct receptor profiles modulated excitability in perilesional versus non-perilesional tissue. Favourable acute motor outcomes were most strongly explained by increased inhibition mediated by non-perilesional GABA-A receptors, together with enhanced excitability driven by cannabinoid, histaminergic, and noradrenergic systems. For acute language outcomes, we identified receptor signatures that, together with motor findings, formed two cross-domain clusters linking excitability to either better or poorer performance. Remarkably, structurally highly connected hubs played a key role: their acute excitability explained cognitive and language deficits and predicted language recovery at one year. Together, our results establish a mechanistic link between receptor-specific modulation of cortical excitability and behavioural recovery, highlighting potential targets for pharmacological and non-invasive therapeutic interventions.

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bioRxiv2026

Spiral brain dynamics track the temporal unfolding of subjective intensity during the N,N-dimethyltryptamine experience

Psychedelic compounds such as N,N-dimethyltryptamine (DMT) induce rapid and profound changes in conscious experience, requiring neuroimaging measures that capture how brain dynamics evolve across space and time. Emerging evidence suggests that rotational (vortex-like) dynamics may contribute to the coordination of large-scale neural activity. Here, we introduce two vorticity-based metrics; spiral vorticity (SV) and spatial spiral vorticity dispersion (SSVD), to quantify the rotational organization and spatial heterogeneity of large-scale cortical phase dynamics. Using fMRI data acquired under placebo and DMT in a within-subject design, we assessed these measures globally, across resting-state networks, and regionally to examine their relationship to subjective intensity. DMT increased SV and SSVD and reduced temporal irreversibility, indicating stronger rotational organization, greater spatial heterogeneity, and altered directional structure of cortical dynamics. Effects were non-uniform across functional systems, with the largest changes in default mode, visual, frontoparietal, and dorsal attention networks. Both vorticity measures tracked the temporal evolution of subjective intensity globally, while network-level analyses revealed spatially heterogeneous brain-experience coupling. Spatiotemporally resolved analyses further showed that the strongest reorganization of spiral dynamics emerged during offset and recovery rather than at peak subjective intensity. These findings identify spiral dynamics as a time-resolved neural signature of the DMT experience. By quantifying the rotational structure and spatial heterogeneity of cortical phase flow, vorticity-based measures provide a framework for linking large-scale brain dynamics to evolving subjective experience.

neuroscience↗

bioRxiv2026

White-matter disconnection shapes distributed cortical spectral dynamics after stroke

Focal brain lesions are thought to induce sleep-like slow-wave activity in perilesional cortex through altered excitation-inhibition balance and structural disconnection, but whether these dynamics extend to remote yet structurally intact regions remain unclear. Here we combined source-reconstructed high-density EEG (128 channels) with structural disconnection mapping in 49 acute stroke patients and 20 age-matched controls. Cortical regions were classified as perilesional, structurally disconnected, or non-disconnected using individual lesion masks registered to normative white-matter atlases. Perilesional cortex showed increased delta and theta power and reduced beta power relative to controls. Critically, structurally disconnected regions exhibited electrophysiological changes comparable to perilesional cortex, including enhanced low-frequency activity and steeper aperiodic spectral slopes. These alterations correlated with neurological severity and multidomain behavioral impairment. Our findings demonstrate that post-stroke slow-wave activity propagates along structural disconnection pathways, providing direct electrophysiological evidence for connectional diaschisis and identifying distributed network targets for physiology-guided neuromodulation.

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bioRxiv2026

Brain dynamics predict oral contraceptive treatment duration

Oral contraceptives are used by millions of women worldwide, yet their cumulative effects on the female brain remain poorly understood. We analyzed resting-state fMRI from 192 women (never, current, and past users) using brain-dynamics metrics that quantify information transfer across spatiotemporal scales. Duration of use was associated with a progressive, age-independent modulation of brain dynamics: prolonged use was related to restricted local synchronization but enhanced information flow across scales. Machine learning predicted individual duration of use from brain dynamics, and node-level classifiers distinguished users from never-users based on a spatially distributed cortical pattern spanning multiple functional networks, most clearly detectable in long-term users. In past users, these associations were inverted in sign, scaling with prior duration rather than returning to the never-user baseline, suggesting active reorganization following cessation. Together, these results indicate that cumulative oral contraceptive exposure acts as a neuromodulator of information processing.

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bioRxiv2026

Flattened brain hierarchy and increased EEG complexity during unusual bodily experiences and out-of-body experiences

Experiences in which the sense of the body becomes distorted offer a unique window into how the brain constructs the bodily self. Despite their clinical relevance in conditions such as depersonalization and body-image disorders, large-scale brain dynamics underlying unusual bodily experiences (UBEs) remain poorly understood, and no prior study has examined them systematically across wakefulness and sleep. Here, we analyzed a high-density EEG dataset including 36 UBE episodes, such as floating sensations, distorted body boundaries, and out-of-body experiences, recorded across rapid eye-movement (REM) sleep, light sleep, sleep arousals, and wakefulness during meditation (N=20). We quantified the temporal irreversibility of neural dynamics, a marker of cortical hierarchical organization, and complemented these analyses with whole-brain signal complexity measures following a within-subject design. UBEs were consistently associated with a global reduction in neural irreversibility and cortical hierarchical differentiation relative to non-UBEs and wakefulness, along with a concurrent increase in whole-brain complexity to levels comparable to wakefulness. Together, these findings suggest that UBEs reflect a neural state combining high informational richness with a transient flattening of cortical hierarchy, a profile that resembles that observed in psychedelic states. Key pointsO_LIUBEs are associated with a global flattening of brain hierarchy measured by EEG. C_LIO_LIUBEs are associated with increased global EEG complexity, resembling the psychedelic state. C_LI

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bioRxiv2026

Hyper-Hierarchical Brain States Are Associated with Disorders of Consciousness

BackgroundConsciousness is increasingly understood as an emergent property of large-scale brain dynamics that depend upon flexible interactions among distributed cortical and subcortical systems. Although disorders of consciousness (DOC) have traditionally been associated with impaired integration and reduced network complexity, the role of hierarchical brain organization in supporting conscious awareness remains poorly understood. Here, we investigated how hierarchical organization relates to behavioral responsiveness in DOC by combining trophic-level analysis, trophic coherence, and whole-brain dynamical metrics. MethodsResting-state functional MRI data were analyzed from healthy controls (CNT), minimally conscious state (MCS) patients, and unresponsive wakefulness syndrome (UWS) patients drawn from a previously published DOC cohort. Static global and regional measures of functional hierarchy were computed from directed effective-connectivity networks. Dynamic trophic states were identified using time-resolved phase-coupling analyses and clustering of recurrent coordination patterns. State occupancy, dwell time, metastability, synchrony, and behavioral associations with Coma Recovery Scale-Revised (CRS-R) scores were evaluated. ResultsRegional trophic levels were positively associated with behavioral responsiveness, with higher frontal and thalamic trophic levels and lower insular trophic levels predicting higher Coma Recovery Scale-Revised (CRS-R) scores. Dynamic trophic-state analysis identified a pathological hyper-hierarchical state, defined by elevated frontal, thalamic, and insular trophic levels, that exhibited progressively greater occupancy and longer dwell times from healthy controls to minimally conscious state and unresponsive wakefulness syndrome patients. In contrast, occupancy and dwell time of this state distinguished diagnostic groups but were not significantly associated with behavioral responsiveness. Independent analyses demonstrated significant reductions in metastability and global synchrony across disorders of consciousness. Anatomical mapping localized elevated trophic levels within the pathological state predominantly to fronto-thalamo-limbic systems. ConclusionsDisorders of consciousness are characterized not simply by loss of hierarchical organization but by prolonged stabilization within recurrent hyper-hierarchical brain states. Conscious awareness appears to depend not only on hierarchical organization itself but also on the capacity to flexibly transition between distinct brain states. Severe disorders of consciousness are associated with persistent occupation of pathological hyper-hierarchical states, potentially restricting the dynamical repertoire available for conscious processing.

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bioRxiv2026

A personalized map of where, when, and how to stimulate the brain to elicit controlled responses

Brain stimulation has transformed the treatment of several neurological and psychiatric disorders and is now widely used to read out causal interactions in the human brain. However, its effects vary from one trial to the next, even when the stimulation parameters are kept identical. Identifying the sources of this variability and developing new strategies to reduce it are key to achieving more controllable interventions. Yet, exhaustive testing in real experiments is unfeasible, because each participant can only be probed at a handful of sites under conditions the experimenter cannot fully control. Here we use personalized brain models to map how stimulation responses vary across target sites and with the brains ongoing state. We show that stimulation responses are jointly determined by the targets position along the cortical unimodal-to-transmodal hierarchy and the brains global ongoing activity, with lower-activity states yielding larger responses. Accordingly, timing stimulation to low-activity periods reduces trial-to-trial variability in response magnitude. Even without state information, joint stimulation of specific region pairs reduces variability compared with stimulating either region alone. Together, these findings identify where, when, and how to stimulate the brain to achieve more reproducible responses, with concrete predictions for closed-loop and circuit-level stimulation protocols.

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bioRxiv2026

Divergent changes in perturbation-induced brain reconfiguration following depression treatment with psilocybin and escitalopram

A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual. Then, we employed systematic and local artificial perturbations across intensities, re-optimised each model to create a response GEC (GECr), and assessed the extent of brain reorganisation by quantifying the brain network reconfiguration index (NRI). Our results showed that the global brain NRI increases with psilocybin and decreases with escitalopram. Across sessions and interventions, higher global NRI was related with localised perturbations in brain areas orchestrating the brains hierarchical dynamics. Traditional approaches complemented our investigation. Our findings suggest distinct neural changes following each treatment for MDD. The increase in brain reorganisation under perturbation following psilocybin is consistent with greater brain flexibility and changeability, whereas the decrease following escitalopram suggests more stabilised brain dynamics. Overall, perturbation-induced brain NRI may represent a useful approach for uncovering neural changes following different interventions for depression.

neuroscience↗

bioRxiv2026

Distinct brain responses to psilocybin and escitalopram in depression captured by the Fluctuation-Dissipation Theorem

In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepressant, escitalopram, from the double-blind randomised controlled trial (DB-RCT) -NCT03429075- on the brains hierarchical organisation. Using pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) we built whole-brain models and obtained a generative effective connectivity (GEC) matrix for each patient. Based on the GEC, we measured the level of non-equilibrium brain dynamics by quantifying the deviation from the fluctuation-dissipation theorem (FDT) and performed complementary analysis on brain segregation and asymmetry. Our results showed opposite reconfigurations of the hierarchical non-equilibrium brain dynamics following each treatment. Additionally, baseline measures effectively distinguished responders from non-responders within each treatment. These findings suggest that the deviation of the FDT may serve as a marker for differentiating the effects of psilocybin and escitalopram in MDD treatment, overall, contributing to the understanding of therapeutic mechanisms of depression.

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bioRxiv2026

Generalisable signatures of anaesthesia in the large-scale functional organisation of the marmoset brain

How the activity and connectivity of the brain support consciousness remains a central question in neuroscience. Recent progress driven by the use of functional MRI has seen growing recognition that large-scale distributed functional organisation of the human and non-human primate brain are systematically and consistently reshaped by anaesthetic-induced unconsciousness, across anaesthetics and across human and macaque. Here, we generalise these results to a different primate species that is gaining traction as model organism in neuroscience, the marmoset (Callithrix jacchus). We also generalise results to an additional anaesthetic, isoflurane, which we compare with propofol and sevoflurane. We report that under anaesthesia with propofol, sevoflurane, or isoflurane, distributed brain activity from functional MRI is increasingly constrained by the underlying structural connectivity across scales. Anaesthesia also induces a collapse of the principal gradient and intrinsic functional geometry of the marmoset brain, coinciding with a breakdown of hierarchical integration. Altogether, the present results indicate generalisable signatures of anaesthesia in the large-scale organisation of the primate brain.

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bioRxiv2026

One operator to rule them all: Unifying connectome harmonics, turbulence and complex harmonics in brain dynamics

Brain dynamics can be described in three different convenient mathematical languages, namely connectome harmonics, turbulence and complex harmonics (CHARM). Here we demonstrate that these theoretical frameworks can be rigorously unified, under the functional calculus, as one self-adjoint operator and its single spectral measure. The connectome Laplacian carries that measure; the harmonics are its spectral projections, the turbulence smoothing kernel is its resolvent, and the CHARM form is its unitary propagator. The bridge that makes this exact is a textbook fact: The exponential distance rule, which is the empirical kernel of the turbulence model, is the Greens function of a screened Laplacian, so the local order parameter is the phase field passed through the resolvent of the same operator whose eigenfunctions are the harmonics. A single shared control parameter, the spectral gap, simultaneously yields the cortical hierarchy, the turbulent information cascade and the structured interference the CHARM form measures. This unification makes a strong predictive claim. If the harmonic projections, the turbulence resolvent and the CHARM propagator really are three functions of one operator, then any structural perturbation that re-tunes the operator must move all three signatures in unison and must do so with a single coupling. We test this prediction with a pharmacological perturbation by lysergic acid diethylamide (LSD), which is known to change the emotional state, by empirically perturbing the operator with a 5-HT2A receptor density map and asking whether one scalar coupling can simultaneously predict the multi-scale turbulence shift observed, through the resolvent, and the macroscale harmonic energy redistribution, through first-order Rayleigh-Schrodinger perturbation theory. We found that the two independent functional domains respond in unison to one structural perturbation of one operator. The identity is exact as operator calculus and its purchase on the brain depends on a single load-bearing seam, the degree heterogeneity of the connectome, which we make explicit. We propose that this single-operator structure is the necessary mathematical scaffolding of our Entangled Loop theory.

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bioRxiv2026

Global nonequilibrium cortical dynamics tie mid-level pupil-linked arousal to optimal task performance in humans

Ongoing fluctuations in brain state, largely driven by neuromodulators of arousal, shape how sensory inputs are processed and decisions are made. Here, we combined pharmacological manipulations and pupillary proxies of arousal to examine how global cortical state dynamics relate to perceptual sensitivity. We applied the thermodynamics-inspired INSIDEOUT framework to electroencephalography (EEG) recordings from two visual discrimination tasks performed under placebo, atomoxetine (noradrenergic enhancer), and donepezil (cholinergic enhancer) challenges. INSIDEOUT quantifies the strength of functional hierarchies within the brain via the computation of temporal irreversibility in neural activity. Trial-wise global irreversibility increased linearly with pupil-indexed arousal and exhibited a nonlinear inverted-U relationship with perceptual sensitivity, while showing no differences across drug conditions. A nonlinear mediation analysis revealed that temporal irreversibility can account for a significant portion of the association between pupil-linked arousal and perceptual sensitivity. At lower arousal, increases in prestimulus irreversibility improved perceptual accuracy, whereas at higher arousal, pre- and poststimulus irreversibility had different effects. These results bridge intrinsic whole-brain dynamics with perceptual decision-making, demonstrating that neuromodulator-linked arousal tunes cortical states and, in turn, perceptual performance. More broadly, the results shed new light on how arousal may reconfigure neural global dynamics.

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bioRxiv2026

Preserved but not functional: growth biology shapes connectivity resilience in meningioma and glioma

Brain tumors disrupt neural connectivity, but the nature of this disruption depends on tumor growth biology. Here, we analyze pre-operative structural connectivity (SC), functional connectivity (FC), and generalized effective connectivity (GEC) in 14 meningioma patients, 10 glioma patients, and 10 matched controls to characterize how extra-axial and intra-axial tumors differentially affect brain networks. We introduce FC resilience, the relative preservation of functional connectivity in structurally damaged regions, and find that meningioma patients exhibit significantly higher FC resilience than glioma patients, with SC-dominant damage and preserved neural activity in damaged regions. Glioma patients show balanced SC-FC damage and degraded neural activity, consistent with infiltrative destruction of both white matter and neural substrate. Connectivity damage is not localized to the tumor vicinity and is non-randomly distributed across functional networks, with distinct propagation patterns: glioma SC damage clusters along white matter pathways, while meningioma SC damage preferentially targets Limbic and Default networks. Network topology analysis reveals that more segregated functional and effective connectivity, particularly higher modularity, predicts FC resilience in meningioma patients but not in glioma patients, while structural connectivity topology shows no predictive value. Non-equilibrium dynamics, quantified via the Fluctuation-Dissipation Theorem, are elevated in damaged regions of meningioma patients, serving as a dynamical marker of structural damage rather than an independent compensatory mechanism. Clinically, higher FC resilience in glioma patients is associated with worse cognitive outcomes, suggesting that preserved FC without an intact neural substrate does not reflect genuine functional preservation. These findings demonstrate that the interpretation of functional connectivity resilience depends fundamentally on tumor type and its underlying growth biology.

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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

Acute perilesional excitability explains long-term motor recovery after stroke

Stroke is a leading cause of disability, and changes in neuronal excitability in perilesional regions may critically influence patients recovery. While reduced excitability is often associated with impaired recovery, increased excitability following injury may support reparative mechanisms. Although animal studies have shown how synaptic transmission adapts after stroke, a mechanistic understanding of how these excitability changes in the perilesional area relate to recovery in acute patients remains unclear. Here, we apply patient-specific (N = 96) computational whole-brain models to infer regional excitability, focusing on both perilesional and non-perilesional sites. Specifically, we estimate the firing sensitivity of local excitatory neuronal populations. Our findings indicate large inter-subject variability, with patients displaying both relative perilesional hypo- and hyper-excitability. Notably, perilesional excitability emerges as a robust predictor (P = 0.002) of motor recovery one year after the stroke, but not of acute post-stroke motor impairment, emphasizing its significance in specifically shaping long-term recovery. This synaptic modulation of excitability exhibits a strong correlation with gamma-aminobutyric acid A (GABA-A) receptor density distributions before the stroke, providing a potential biological substrate. These findings highlight the subject-specific nature of perilesional excitability, positioning it as a compelling target for personalized interventions to optimize post-stroke motor recovery.

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bioRxiv2026

A generalized scaling law to characterize coordinated brain activity

Complex ecological systems obey universal scaling laws such as Taylors law, which links population variance to the sample mean. Whether other complex systems with integrated and segregated functional networks--such as the human brain--follow analogous scaling laws, and how these laws behave under synchronized activity, remains unknown. Progress has been hindered because neural signals at all measurement scales contain both positive and negative values, whereas Taylors law was developed for non-negative ecological data. Here we introduce a generalized spatial scaling law that replaces the sample mean with the root-mean-square (RMS) of detrended activity, extending Taylor-like scaling to signed multivariate time series in neural and other complex systems. Within this framework, we quantify synchrony using a dedicated metric of functional coordination and show analytically, and via numerical simulations using multivariate Poisson, binomial, uniform and gamma distributions, that the scaling exponent is inversely related to synchrony. Applying this approach to human fMRI data from three large lifespan cohorts (N = 840, ages 18-88) reveals distinct age-related trajectories of the scaling exponent, with healthy aging characterized by a substantial synchrony-induced reduction in the exponent. The synchrony-scaling relationship remains stable during resting-state activity but progressively shifts during naturalistic tasks across the lifespan, and is particularly strong in limbic, subcortical, and cerebellar subnetworks, indicating preservation at subnetwork levels. Finally, individuals with ADHD exhibit disrupted synchrony-scaling coupling, highlighting the potential clinical and translational utility of this generalized scaling metric.

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