Biology subjects

Timmermann, C.

Publications and source records attributed to Timmermann, C..

At least 19 recordsLinked to original sources

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.

neuroscience↗

bioRxiv2026

Psychedelics restructure information in the human brain

How do psychedelic drugs alter human brain function? Answering this question relies on our ability to understand how information is stored, transferred, and transformed across the cortex. Here, we leverage a precise mathematical framework for multivariate information decomposition to construct the first comprehensive picture of these processes across five compounds: LSD, psilocybin, ketamine, DMT and 5-MeO-DMT (N=80). We provide a formal and empirical explanation of major prior results, revealing sets of competing underlying phenomena masked by extant approaches. We extend this analysis to novel higher-order phenomena, and we demonstrate how all of these observations can emerge from a minimal generative model in which neural populations operate with reduced self-coupling. In sum, our results suggest that the psychedelic brain is one in which cortical populations become alike, but not necessarily together. This has important implications for models of how psychedelics reorganize brain dynamics to alter subjective experience and alleviate mental health conditions.

neuroscience↗

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

What is it like to be a blob? A distributed, decentred and context-sensitive neurobiology of consciousness

Consciousness is often studied by asking whether particular brain regions or systems are privileged. We tested a distributed, decentred and context-sensitive alternative using 579 consciousness-focused neuroimaging studies. Semantic clustering of titles and abstracts identified seven domains whose corrected meta-analytic maps showed limited overlap and no invariant cross-domain core. These maps occupied 18.0% of grey matter while extending across 91.0% of brain regions. After controlling for reporting topography, distributed cognitive, sensorimotor and organismic-affective maps reconstructed the residual consciousness landscape better than spatial surrogates. Organismic-affective maps contributed most, but functional contributions varied contextually across domains. Theory-associated regional loci added no additional meaningful prediction. Information carried by the functional families was both redundant and synergistic. Coactivation-network and hypergraph analyses revealed a shared network repertoire but context-dependent higher-order coalitions. These results argue against an invariant core, supporting a distributed neurobiology of consciousness in which specialised systems are weighted and combined differently across contexts.

neuroscience↗

bioRxiv2026

A Shared Entropic Axis Spans States of Consciousness Across Pharmacological and Clinical Conditions

A general account of how diverse states of consciousness arise from brain activity requires a quantitative framework that generalises across them. The Entropic Brain Theory proposes that states of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, but this prediction has not been tested across pharmacological and clinical perturbations within a common analytical pipeline. Here we quantify the temporal irregularity of time-resolved small-world topology using sample entropy, applying the same pipeline to pharmacological (psychedelics, modafinil, propofol anaesthesia) and clinical (schizophrenia) fMRI datasets. Propofol anaesthesia occupied the low-entropy end of the axis; psychedelic states and schizophrenia occupied the high end. The ordering tracks combined modulations of the level and content of consciousness, ranging from reduced awareness under anaesthesia to the heightened arousal and expanded experience of psychedelic states and the disorganised, dysregulated processing of schizophrenia. Crucially, this result was not reducible to fluctuations in mean functional connectivity, and was supported by convergent reorganisation of higher-order association cortex under psychedelics and anaesthesia, alongside a distributed loss of network specificity in schizophrenia. These findings provide cross-condition empirical support for an entropic continuum of brain states and identify the temporal diversity of large-scale network reconfiguration as a primary axis of conscious dynamics.

neuroscience↗

bioRxiv2026

Reorganization of Human Brain Waves Across Diverse States of Consciousness

Brain waves are ubiquitous phenomena of human brain activity. As they propagate, they coordinate neural communication, shaping conscious perception. Understanding how brain waves unfold across space and time is thus critical for uncovering the neural mechanisms that support and suppress consciousness. Here, we analyzed data from the Human Connectome Project alongside multiple independent human datasets of various states of consciousness collected during non-rapid eye movement sleep, propofol anesthesia, and psychedelic states produced by lysergic acid diethylamide, N,N-dimethyltryptamine, psilocybin, nitrous oxide, and ketamine. We then applied complex principal component analysis to map spatiotemporal propagation patterns of blood oxygen level-dependent activity across the human brain, under these diverse states of consciousness. We identified four dominant motifs of wave propagation: a global synchronized wave supporting unimodal-transmodal propagation, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave. Among them, the global wave exhibited the most pronounced state-dependent reconfiguration: in diminished states (sleep and anesthesia), the time needed for the wave to propagate across brain regions consistently increased and the distribution of regional contributions to the waves power became more spatially concentrated and heterogeneous across individuals, indicating slower, more fragmented, and less stereotyped dynamics. In contrast, propagation duration decreased under psychedelic states, reflecting accelerated global wave dynamics alongside a trend towards more spatially distributed and uniform regional contributions, consistent with a more integrated global wave propagation pattern. Beyond this global mode, diminished states slowed propagation primarily along the unimodal-transmodal axis, whereas psychedelic states selectively accelerated propagation along the task-positive/task-negative axis. Together, our findings reveal that diminished (sleep and anesthesia) and psychedelic states alter the spatiotemporal structure of wave propagation across the brain in opposite and distinct ways, providing a unifying account of how macroscale brain dynamics are dynamically reshaped under pharmacological and endogenous perturbations of consciousness.

neuroscience↗

bioRxiv2025

A Mesoscale Framework for Psychedelic Drug Action in the Human Brain

The mechanism of psychedelic drug action is a dynamic area of neuroscience, with two major lines of investigation: (1) laboratory studies at the molecular and cellular level, and (2) human neuroimaging studies of functional brain networks. Despite considerable progress, there remains insufficient understanding of the link between molecular/cellular substrates of psychedelics and the whole-brain network effects that result. Here we report a study of psychedelic action that focuses on the intermediate spatial scale of local brain regions (<1cm3). We analyzed the effects of classical psychedelics (dimethyltryptamine [DMT], lysergic acid diethylamide [LSD], psilocybin) and non-classical psychedelics (nitrous oxide, ketamine) in humans using functional magnetic resonance imaging. We found that all five drugs reduced regional homogeneity, that is, they disrupted local synchrony, in small-scale brain regions; this disruption occurred extensively in cortical regions and sparsely in subcortical regions. Dynamic analysis of both regional homogeneity and global functional connectivity showed an inverse pattern, with large-scale functional connectivity being enhanced as local synchrony declined. We then conducted dominance analysis to assess the contribution of various neurotransmitter receptors to changes in regional homogeneity. DMT, LSD, and psilocybin showed the 5-HT receptors as the most dominant association; by contrast, regional homogeneity changes attributable to both nitrous oxide and ketamine were most strongly associated with the NMDA receptor. Both neuronal (including interneurons) and non-neuronal cell types were linked to psychedelic-induced changes in synchrony at the level of local brain regions. These data, across five drugs from two drug classes, provide evidence that a diverse set of molecular and cellular events lead to a common outcome of disrupted synchrony in local brain regions, which in turn mediate drug-specific changes in global functional connectivity.

neuroscience↗

bioRxiv2025

"Awe-scillations": EEG spectral and complexity representations of awe

Awe is a positive emotion often accompanied by sensations of vastness and unity, with known benefits for well-being and social behavior. However, its neural underpinnings remain poorly understood. We recorded electroencephalography (EEG) and autonomic physiology in 23 healthy older participants while they watched a nature-based audiovisual film and subjectively rated awe events. Awe was the predominant emotion reported - though other positive emotions (e.g., joy) were also highly rated. Awe events were associated with decreased skin conductance level (SCL), and decreased EEG alpha and theta spectral power - physiological changes associated with low arousal and positively valenced emotional states. Interestingly, awe events exhibited increased Lempel Ziv Complexity (LZC) - indicating heightened neural signal entropy and increased richness of the conscious experience. LZC was also positively associated with the intensity of the awe ratings and negatively associated with SCL. Three additional datasets with separate independent induction methods (video clips and pharmacological induction via N,N-dimethyltryptamine) also showed positive occipital LZC associations with awe - suggesting some generalizability of LZC as a neurophysiological marker of awe. These results suggest that awe evokes neurophysiological states linked to the subjective affective experience. Impact StatementAwe, an emotion of increasing interest, has been studied with fMRI and peripheral physiology - but few studies have used electroencephalography (EEG). In this EEG study, we utilize a movie-watching paradigm to explore potential physiological correlates of awe. The results present EEG-based complexity increases as a potential correlate of awe, though showing limited generalization to independent datasets and limited uniqueness compared to joy, another positive emotion.

neuroscience↗

bioRxiv2025

Autonomic Indicators of Self-Transcendence: Insights from the Numadelic VR Paradigm

Self-transcendent experiences (STEs) offer profound and beneficial shifts in perspective, yet remain largely inaccessible outside elite contemplative or pharmacological contexts. Neural measures have deepened our understanding of these states, but their cost and limited ecological validity constrain broader application. This study evaluates heart rate variability (HRV) amplitude, a measure reflecting dynamic sympathovagal engagement, as a cost-effective and sustainable physiological marker of STE during numadelic virtual reality (VR) experiences. The unique numadelic aesthetic combined with multi-person can induce STE through dissolving self-boundaries and fostering embodied presence. Building on previous work linking non-ordinary states of consciousness (NOSC) with autonomic nervous system activity during psychedelic drug administration, we tested the hypothesis that HRV amplitude may reflect STE depth and relate to affective and relational outcomes during non-drug numadelic VR experiences. Specifically, ninety-six participants engaged in guided meditation within either a numadelic VR setting or a non-VR audio-guided group format. Physiological data (cardiac activity and respiration) were recorded during the meditation, alongside psychological assessments pre- and post-session. Findings confirm that HRV amplitude measured during numadelic VR correlates with subjective STE ratings. It also relates to compassion traits, and emotional improvement following VR practice. Additional analysis of data from a prior psychedelic drug study further validated the relevance of this measure across methods of inducing NOSCs. These results advance the psychophysiological mapping of STEs and highlight HRV amplitude as a potential real-time biomarker which may help to guide participants toward self-transcendent states within adaptive environments. By integrating contemplative science with immersive design, this work supports the development of scalable tools that enhance both access to and understanding of STEs.

neuroscience↗

bioRxiv2025

DMT-induced shifts in criticality correlate with ego-dissolution

Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain oscillations, and in relation to subjective experience. We find that DMT shifts the dynamics of brain oscillations away from criticality in alpha and adjacent frequency bands. In this context, entropy is increased while complexity is reduced. We find that the criticality shifts observed in alpha and theta bands correlate with the intensity ratings of ego-dissolution, a hallmark of psychedelic experience. Finally, using a recently developed metric, the functional excitatory-inhibitory ratio, we find that the DMT-induced criticality shift in brain oscillations is towards subcritical regimes. These findings have major implications for the understanding of psychedelic mechanisms of action in the human brain and for the neurological basis of altered states of consciousness.

neuroscience↗

bioRxiv2024

Collapse of directed functional hierarchy under classical serotonergic psychedelics

Despite divergent behavioral and phenomenological profiles, both psychedelic states and reduced states of consciousness have been associated with a flattening of the brains functional hierarchy. To address this apparent paradox, we developed a more specific definition of hierarchy based on the proximity of the brain to thermodynamic equilibrium and then applied it to investigate the changes to the functional hierarchy elicited by three classical serotonergic psychedelics - psilocybin, lysergic acid diethylamide, and dimethyltryptamine. We found that all three psychedelics consistently induced a global reduction in the functional hierarchy. In contrast to the flattening of the functional hierarchy observed during loss of consciousness, psychedelics displaced the brain towards equilibrium while simultaneously increasing the complexity of neural activity, indicating a unique mechanism linked to specific changes in the configuration and differentiation of resting-state networks. This work showcases how metrics based on statistical mechanics can be used for the specific characterization of different global brain states, contributing to the understanding of consciousness as a collective process emerging from complex neural interactions.

neuroscience↗

bioRxiv2024

Human brain changes after first psilocybin use

Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1- and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin placebo dose.

neuroscience↗

bioRxiv2024

Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT

Exploring the intricate relationship between brains structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome -- a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under DMT is reshaped in line with other reported psychedelic compounds - psilocybin, LSD and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics indexes the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.

neuroscience↗

bioRxiv2024

Autonomic Nervous System activity correlates with peak experiences induced by DMT and predicts increases in wellbeing

Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called peak experiences, characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extant changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT). We derived measures of SNS and PNS activity from the electrocardiogram data of 17 participants (11 males, 6 females, mean age = 33.8 y, SD = 8.3) while they received either DMT or placebo. Results show that the joint influence of SNS and PNS ( sympatho-vagal coactivation) over cardiac activity was robustly correlated with participants ratings of Spiritual Experience and Insightfulness during the DMT experience, while also being related to improved wellbeing scores two weeks after the session. In addition, we found that the state of balance between the two ANS branches ( sympatho-vagal balance) before DMT injection predicted scores of Insightfulness during the DMT experience. These findings demonstrate the important involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic-therapy. Significance statementPsychedelics can give rise to intense positive subjective experiences - aligned with Maslows notion of peak experiences - that can have a positive and enduring impact on mental health. Understanding how these experiences relate to peripheral physiology before and during the acute effects of psychedelics is an important object of enquiry, as it may help advance the therapeutic use of these compounds. In this study, we demonstrate that specific peripheral states computed from heart rate activity recordings predicted and correlated with acute peak experiences and increases in wellbeing. These findings have implications for the relationship between peripheral physiology and altered states of consciousness. Moreover, they highlight a putative marker of physiological readiness prior the psychedelic experience that could predict therapeutically relevant mechanisms that might be modified to improve mental health outcomes in psychedelic-therapy.

neuroscience↗

bioRxiv2024

Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity - and linked autonomic physiology - naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. fMRI data was preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates; EKG data was used to derive continuous heart rate. We identified a brain substate occurring immediately after DMT injection, characterized by hippocampal and medial parietal deactivations and increased superior temporal lobe activity under DMT. Deactivations in the hippocampus and medial parietal cortex correlated with alterations in the usual sense of time, space and self-referential processes, reflecting a deconstruction of essential features of ordinary consciousness. Superior lobe activations instead correlated with audio/visual hallucinations and experience of "entities", reflecting the emergence of altered sensory experiences under DMT. Finally, increased heart rate under DMT correlated positively with hippocampus/medial parietal deactivation and the experience of "entities", and negatively with altered self-referential processes. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parietal deactivations under DMT, which combined, may contribute to positive mental health outcomes related to self-referential processing following psychedelic administration.

neuroscience↗

bioRxiv2024

DMT induces a transient destabilization of whole-brain dynamics

The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We used a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we parametrized the proximity to a global bifurcation using a pharmacokinetic equation. Simulated perturbations revealed a transient of heightened reactivity concentrated in fronto-parietal regions and visual cortices, correlated with serotonin 5HT2a receptor density, the primary target of psychedelics. These advances suggest a mechanism to explain key features of the psychedelic state and also predicts that the temporal evolution of these features aligns with pharmacokinetics. Our results contribute to understanding how psychedelics introduce a transient where minimal perturbations can achieve a maximal effect, shedding light on how short psychedelic episodes may extend an overarching influence over time.

neuroscience↗

bioRxiv2023

The entropic heart: Tracking the psychedelic state via heart rate dynamics

A growing body of work shows that autonomic signals provide a privileged evidence-stream to capture various aspects of subjective and neural states. This work investigates the potential for autonomic markers to track the effects of psychedelics -- potent psychoactive drugs with important scientific and clinical value. For this purpose, we introduce a novel Bayesian framework to estimate the entropy of heart rate dynamics under psychedelics. We also calculate Bayesian estimates of mean heart rate and heart rate variability, and investigate how these measures relate to subjective reports and neural effects. Results on datasets covering four drugs -- lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), psilocybin, and sub-anaesthetic doses of the dissociative agent ketamine -- show consistent increases in mean heart rate, high-frequency heart rate variability, and heart rate entropy during the psychedelic experience. Moreover, these effects have predictive power over various dimensions of the psychedelic experience. Changes in heart rate entropy were found to be correlated with increases in brain entropy, while other autonomic markers were not. Overall, our results show that a cost-efficient autonomic measure has the potential to reveal surprising detail about subjective and brain states, opening up a range of new research avenues to explore in both basic and clinical neuroscience.

physiology↗

bioRxiv2023

Harmonic decomposition of spacetime (HADES) framework characterises the spacetime hierarchy of the DMT brain state

The human brain is a complex system, whose activity exhibits flexible and continuous reorganisation across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. In this study, we develop the Harmonic Decomposition of Spacetime (HADES) framework that characterises how different harmonic modes defined in space are expressed over time, and, as a proof-of-principle, demonstrate the sensitivity and robustness of this approach to specific changes induced by the serotonergic psychedelic N,N-Dimethyltryptamine (DMT) in healthy participants. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni- to transmodal functional hierarchy of the brain, supporting the hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state.

neuroscience↗