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bioRxiv Preprint Server

202 papers in the library · 574 citations · publishing 2015-2026

Papers

In the Body’s Eye: The Computational Anatomy of Interoceptive Inference

bioRxiv Preprint Server April 10, 2019 Micah Allen, Andrew Levy, Thomas Parr et al. 100 citations preprint

A formal model of cardiac active inference explains how signals from the heart influence perception of the outside world and confidence in that perception. Simulated experiments reproduce the defensive startle reflex and the link between the cardiac cycle and fear perception. Simulated interoceptive lesions reduce fear expectations, cause psychosomatic hallucinations, and worsen metacognitive biases. Synthetic heart-rate variability analyses show how the balance of arousal-priors and visceral prediction errors creates distinct patterns of physiological reactivity. The model provides a way to computationally characterize disordered brain-body interaction.

Are the neural correlates of consciousness in the front or in the back of the cerebral cortex? Clinical and neuroimaging evidence

bioRxiv Preprint Server March 19, 2017 Melanie Boly, Marcello Massimini, Naotsugu Tsychiya et al. 56 citations preprint

The role of the frontal cortex in consciousness is debated. This perspective critically reviews clinical and neuroimaging evidence on whether the front or back of the cortex specifies conscious contents, and discusses promising research avenues. The authors argue that current evidence does not clearly support a primary role for the frontal cortex in generating conscious experience, pointing instead to posterior regions as more directly involved. They suggest that future research should focus on distinguishing neural correlates of consciousness from prerequisites and consequences.

A theory of working memory without consciousness or sustained activity

bioRxiv Preprint Server December 14, 2016 Darinka Trübutschek, Sébastien Marti, Andrés Ojeda et al. 47 citations preprint

Working memory and conscious perception are often thought to rely on the same brain mechanisms, but recent evidence suggests non-conscious working memory exists. Using visual masking and magnetoencephalography in a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance after a long delay. Conscious perception and conscious working memory showed sustained alpha/beta desynchronization over frontal cortex and decodable target location in posterior sensors. During non-conscious working memory, these signals vanished, contradicting models equating working memory with sustained neural firing. The findings support 'activity-silent' working memory, where slowly decaying synaptic changes allow cell assemblies to go dormant during the delay yet be retrieved above chance after seconds.

The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype

bioRxiv Preprint Server March 7, 2021 Urszula Kozłowska, Aleksandra Klimczak, Kalina Wiatr et al. 27 citations preprint

Two classic psychedelics, DMT and psilocin, can alter the behavior of microglia—the brain's immune cells—by reducing levels of immune response markers (TLR4, p65, CD80) and increasing the neuroprotective receptor TREM2. Psilocin also protected neurons in a lab model by reducing microglial phagocytosis. The findings suggest that psychedelics or their analogs may be candidates for treating neurological disorders where inflammation and microglia play a key role.

Drawing the experience dynamics of meditation

bioRxiv Preprint Server March 4, 2022 Barbara Jachs, Manuel Camino Garcia, Andrés Canales-Johnson et al. 21 citations preprint

A new method called Temporal Experience Tracing captures aspects of conscious experience continuously over time, allowing computational reconstruction of common experience states. Analyzing 852 meditations from 20 novice and 12 experienced meditators practicing Breathing, Loving-Kindness, and Open-Monitoring meditation, four recurring experience states were identified, averaging 6 minutes 46 seconds each. Three states matched the three meditation styles, and a fourth represented a low-motivational off-task state. Both groups spent more time in the task-related state during Loving-Kindness meditation and were less likely to transition to the off-task state compared to Breathing meditation. The method transforms the time dimension of subjective experience from narrative to measurable.

The Consciousness Theories Studies (ConTraSt) database: analyzing and comparing empirical studies of consciousness theories

bioRxiv Preprint Server June 10, 2021 Itay Yaron, Lucia Melloni, Michael Pitts et al. 21 citations preprint

A bird's-eye analysis of 412 experiments on the neuroscience of consciousness reveals that methodological choices alone can predict which of four leading theories a study will support, regardless of the actual findings. Most studies interpret their results after the fact rather than testing critical predictions in advance. This suggests that the field's theoretical commitments may be driven more by how experiments are designed than by the evidence itself. The authors provide an open-access website for further exploration of these trends.

Bistability of prefrontal states gates access to consciousness

bioRxiv Preprint Server January 29, 2020 Abhilash Dwarakanath, Vishal Kapoor, Joachim Werner et al. 15 citations preprint

Access of sensory information to consciousness depends on neural activity crossing a threshold in the prefrontal cortex (PFC), yet how brain state fluctuations interact with conscious content is unclear. Using multielectrode recordings during a no-report binocular rivalry task in animals, two distinct prefrontal states were identified: low-frequency (1-9 Hz) bursts that precede spontaneous switches in conscious perception (perceptual update), and beta-band (20-40 Hz) bursts correlated with stable perception. Beta bursts synchronize neural ensembles coding the perceived stimulus. Similar fluctuations occur during rest, suggesting they are endogenous. The findings indicate that global cortical states, not selective spiking, drive internal switches in conscious perception.

Focus on the breath: Brain decoding reveals internal states of attention during meditation

bioRxiv Preprint Server June 17, 2020 H.y. Weng, J.a. Lewis-Peacock, F.m. Hecht et al. 9 citations preprint

Multi-voxel pattern analysis (MVPA) of fMRI data can identify five different internal attention states—breath attention, mind wandering, self-referential processing, attention to feet, and attention to sounds—in individual participants with accuracy well above chance (41% vs. 20% chance). In a mixed sample of 16 experienced meditators and novice controls, classifiers trained during a directed attention task successfully recognized these states in 87.5% of participants. When applied to a separate 10-minute meditation session, the classifiers indicated that participants spent more time attending to breath than to mind wandering or self-referential processing. The findings demonstrate the feasibility of using MVPA to objectively measure internal mental states during meditation at the individual level.

Structure-based Discovery of Conformationally Selective Inhibitors of the Serotonin Transporter

bioRxiv Preprint Server June 13, 2022 Isha Singh, Anubha Seth, Christian B. Billesbølle et al. 8 citations preprint

The serotonin transporter (SERT) adopts three conformations, and most antidepressants target its outward-open state. Ibogaine, which targets the inward-open state, has an unusual antidepressant profile but is cardiotoxic. Computational docking of over 200 million small molecules against the ibogaine-stabilized inward-open SERT identified 36 top compounds; 13 inhibited SERT with potencies from 29 to 5000 nM. Optimization yielded two inhibitors with Ki values as low as 3 nM that stabilized an outward-closed state and showed little off-target activity. A cryo-EM structure confirmed the predicted binding geometry. In mice, both compounds showed anxiolytic and antidepressant activity with potencies up to 200 times greater than fluoxetine.

Trauma Under Psychedelics: How Psychoactive Substances Impact Trauma Processing

bioRxiv Preprint Server March 28, 2024 Ophir Netzer, Noa Magal, Yonatan Stern et al. 7 citations preprint

Survivors of the October 7, 2023 Supernova festival attack in Israel who were under the influence of MDMA during the trauma reported feeling less overwhelmed, had more social interactions, better sleep quality, and reduced psychological distress compared to survivors not using any substance. In contrast, those who consumed cannabis or alcohol during the attack reported higher psychological distress, more PTSD symptoms, and worse sleep quality. The findings suggest MDMA's known effects of reducing negative emotions and increasing prosociality may have buffered trauma impact, while cannabis and alcohol had deleterious effects. The study included 772 adult survivors assessed one to four months after the attack.

Whole-brain modelling supports the use of serotonergic psychedelics for the treatment of disorders of consciousness

bioRxiv Preprint Server December 29, 2023 I Mindlin, R Herzog, L Belloli et al. 7 citations preprint

Disorders of consciousness involve impaired awareness with few non-invasive treatment options. Researchers used computer models to simulate how activating certain receptors, particularly serotonergic and opioid receptors, alters whole-brain dynamics in patients. The simulations shifted patients' brain activity patterns toward those seen in conscious, awake individuals. This effect depended on the density of activated receptors across the brain. The results suggest whole-brain modeling can help identify new pharmacological treatments and support the potential of serotonergic psychedelics to accelerate recovery of consciousness.

Ketamine and sleep modulate neural complexity dynamics in cats

bioRxiv Preprint Server June 25, 2021 Claudia Pascovich, Santiago Castro-Zaballa, Pedro A.M. Mediano et al. 7 citations preprint

Neural complexity, measured by the Lempel-Ziv compression algorithm, is lowest during NREM sleep and similar during REM sleep and wakefulness in cats with intracranial electrodes. Under subanesthetic doses of ketamine (5, 10, and 15 mg/kg), complexity follows an inverted U-shaped curve in some electrodes, especially in prefrontal cortex, rising at low doses and falling as doses approach anesthetic levels. Variability in the ketamine dose-response across cats and cortices is larger than sleep-stage differences, revealing distinct local dynamics. These results replicate findings in humans and other species, showing neural complexity is sensitive to conscious state changes and dose-dependent ketamine effects.

LSD’s effects are differentially modulated in arrestin knockout mice

bioRxiv Preprint Server February 4, 2021 Ramona M. Rodriguiz, Vineet Nadkarni, Christopher R. Means et al. 7 citations preprint

Lysergic acid diethylamide (LSD) produces its psychedelic effects through the 5-HT2A serotonin receptor, which activates two signaling pathways: Gq and β-arrestin. Using mice lacking either β-arrestin1 or β-arrestin2, the authors show that LSD's psychedelic-like behaviors—head twitches, retrograde walking, nose poking, and disrupted prepulse inhibition—require β-arrestin2, not β-arrestin1. LSD also affects motor activity and body temperature in a β-arrestin-dependent manner. The 5-HT2A antagonist MDL100907 blocks these effects in wild-type mice, but in β-arrestin1-knockouts, haloperidol is needed to restore prepulse inhibition. These findings indicate that LSD's diverse behavioral actions are mediated through distinct β-arrestin subtypes, with β-arrestin2 necessary for its psychedelic-like effects.

EEG alpha-theta dynamics during mind wandering in the context of breath focus meditation: an experience sampling approach with novice meditation practitioners

bioRxiv Preprint Server October 23, 2020 Julio Rodriguez-Larios, Kaat Alaerts 7 citations preprint

Mind wandering during breath focus meditation is linked to specific changes in brain waves. In 25 novice meditators, episodes of mind wandering showed increased amplitude and decreased frequency of theta oscillations (4-8 Hz), while alpha oscillations (8-14 Hz) decreased in amplitude and increased in frequency. Mind wandering also involved greater harmonicity and phase synchrony between theta and alpha rhythms. These spectral changes resemble those seen in controlled cognitive processes like memory and executive control, suggesting shared neurocognitive mechanisms. The findings indicate that theta-alpha oscillatory activity could serve as a basis for EEG-neurofeedback protocols to detect mind wandering during meditation.

Migraine aura, a predictor of near-death experiences in a crowdsourced study

bioRxiv Preprint Server October 21, 2019 Daniel Kondziella, Markus Harboe Olsen, Coline L. Lemale et al. 7 citations preprint

Near-death experiences (NDE) are poorly understood but may involve rapid eye movement (REM) sleep intrusion, a feature of narcolepsy. Because migraine with aura is linked to narcolepsy and REM abnormalities, this study tested whether NDE are more common in people who have migraine with aura.

Locomotor and Reinforcing Effects of Pentedrone, Pentylone and Methylone in Rats

bioRxiv Preprint Server July 21, 2017 Mehrak Javadi-Paydar, Jacques D. Nguyen, Sophia A. Vandewater et al. 7 citations preprint

Second generation synthetic cathinones pentedrone and pentylone produce dose-dependent increases in locomotion in male and female Wistar rats, with the maximum effect similar across drugs but lasting longest after pentedrone. Body temperature remained stable after pentedrone or pentylone, while methylone caused sustained hyperthermia in male rats. Rats self-administered more pentedrone or pentylone than methylone, but all three were less potent than α-PVP or α-PHP. These results suggest that pentedrone and pentylone have greater abuse liability than methylone.

Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system

bioRxiv Preprint Server April 12, 2023 Malika S. Datta, Yannan Chen, Shradha Chauhan et al. 6 citations preprint

Repeated ketamine administration causes opposite effects on dopamine neurons in different brain regions: a decrease in midbrain areas linked to behavior states and an increase in the hypothalamus. It also alters nerve connections to the prefrontal cortex, striatum, and sensory areas. The findings suggest post-transcriptional regulation of structural plasticity. An unbiased whole-brain analysis reveals divergent brain-wide impacts of chronic ketamine on association and sensory pathways.

From autopoiesis to self-optimization: Toward an enactive model of biological regulation

bioRxiv Preprint Server February 5, 2023 Tom Froese, Natalya Weber, Ivan Shpurov et al. 6 citations preprint

The theory of autopoiesis, influential in theoretical biology and origins of life, has struggled to connect with mainstream biology due to challenges in generating testable hypotheses. Recent developments in the enactive approach have clarified concepts like precariousness, adaptivity, and agency. This paper advances those ideas by integrating thermodynamic principles—reversibility, irreversibility, and path-dependence—and interpreting them through a self-optimization model. Modeling results show how minimal conditions allow a system to reorganize toward coordinated constraint satisfaction. Although abstract, these findings suggest a path for the enactive approach to productively engage with cell biology.

Gut markers of bodily self-consciousness

bioRxiv Preprint Server March 5, 2021 Alessandro Monti, Giuseppina Porciello, Maria Serena Panasiti et al. 6 citations preprint

Bodily self-consciousness, the awareness of one's own body, is fundamental to human experience but poorly understood. By combining an ingestible capsule that measures gut activity (temperature, pressure, pH, and gastric peak frequency) with surface electrogastrography during a virtual bodily illusion, specific patterns of stomach and bowel activity were found to covary with distinct facets of bodily self-consciousness, such as feelings of body agency, location, and disembodiment. These findings reveal a link between gut physiology and the self-conscious perception of being embodied, demonstrating the potential of minimally invasive probes for studying mind-gut connections.

Topological Analysis of Differential Effects of Ketamine and Propofol Anesthesia on Brain Dynamics

bioRxiv Preprint Server April 4, 2020 Thomas F. Varley, Vanessa Denny, Olaf Sporns et al. 6 citations preprint

The vividness of conscious experience is linked to brain dynamics. Propofol and ketamine, both anesthetics, produce different subjective states. This study examined how these drugs alter the structure of dynamic attractors reconstructed from electrical brain activity recorded from the cerebral cortex of two macaques. The awake condition showed the richest structure, visiting the most states with pronounced higher-order dynamics and the least deterministic activity. Propofol produced the most dissimilar dynamics, shifting to an impoverished, constrained, low-structure regime. Ketamine combined aspects of both: generally less complex than awake but well above propofol on almost all measures. These results offer deeper insights than typical point-measures of complexity.

Distinct Hierarchical Alterations of Intrinsic Neural Timescales Account for Different Manifestations of Psychosis

bioRxiv Preprint Server February 7, 2020 Kenneth Wengler, Andrew T. Goldberg, George Chahine et al. 6 citations preprint

Hallucinations and delusions in schizophrenia may arise from distinct alterations in how the brain integrates information over time across different levels of sensory processing hierarchies. Using resting-state fMRI to measure intrinsic neural timescale (INT), which reflects the time window of neural integration, researchers found that hallucinations were linked to altered INT in lower auditory and somatosensory regions, while delusions were associated with changes in higher hierarchical areas. Computer simulations suggested that local imbalances between excitation and inhibition at different hierarchical levels could underlie these patterns. The findings support hierarchical perceptual-inference models of psychosis and demonstrate INT as a useful tool for studying brain hierarchies.

Rhythms of the Body, Rhythms of the Brain: Respiration, Neural Oscillations, and Embodied Cognition

bioRxiv Preprint Server August 9, 2017 Somogy Varga, Detlef H. Heck 6 citations preprint

Respiration, despite being a constant rhythmic bodily process, has been largely overlooked in Embodied Cognition research. This paper argues that breathing exerts a significant, unexpected bottom-up influence on cognitive processes by modulating neural synchronization. The authors propose respiration as a model for a general mechanism through which the body affects cognition. They also suggest that respiration can play a dual pragmatic and epistemic role, reducing cognitive load through a loop-like interaction between neural and non-neural elements, drawing a parallel to the role of gesture.

Neural correlates of pure presence

bioRxiv Preprint Server April 18, 2024 Melanie Boly, Richard Smith, Giulietta Vigueras Borrego et al. 5 citations preprint

A state called pure presence, reported in meditative traditions as a vivid experience without thoughts, perceptions, or self, was examined in twenty-two long-term meditators using high-density EEG. During pure presence, brain activity showed widespread reductions in gamma and delta power compared to mind-wandering, watching a movie, active thinking, and dreamless sleep. The strongest gamma decreases occurred in the posteromedial cortex. These findings align with integrated information theory's prediction that vivid consciousness can arise when the brain's cortical substrate is largely quiet yet highly awake.

Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors

bioRxiv Preprint Server April 3, 2024 Elie Adam, Marek Kowalski, Oluwaseun Akeju et al. 5 citations preprint

Ketamine, an NMDA-receptor antagonist, produces sedation, analgesia, and dissociation at low doses and unconsciousness at high doses, generating gamma oscillations (>25 Hz) in the EEG at both doses, with slow-delta oscillations (0.1-4 Hz) interrupting gamma at high doses. Using a biophysical model of cortical circuits, the authors show how NMDA-receptor antagonism by ketamine leads to disinhibition in neuronal circuits, and how the disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition generates gamma oscillations at both doses and slow-delta oscillations at high doses. This work reveals general mechanisms for oscillatory brain dynamics distinct from previous reports and offers insights into ketamine's action as an anesthetic and therapy for treatment-resistant depression.

Exploring the embodied mind: functional connectome fingerprinting of meditation expertise

bioRxiv Preprint Server December 6, 2023 Sébastien Czajko, Jelle Zorn, Loïc Daumail et al. 5 citations preprint

Short mindfulness-based interventions improve well-being, cognition, and clinical symptoms, but they are considered early steps on a longer transformative path that may produce lasting trait changes. Little is known about the brain correlates of these meditation traits.