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bioRxiv Preprint Server

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

Papers

Dynamical independence reveals anaesthetic specific fragmentation of emergent structure in neural dynamics

bioRxiv Preprint Server July 16, 2025 Borjan Milinkovic, Anil K. Seth, Lionel Barnett et al. 2 citations preprint

Consciousness depends on neural activity across many scales. A new measure, dynamical independence (DI), quantifies these multi-scale relationships. Applying DI to EEG data from people under three anaesthetics, the authors found that propofol and xenon—which abolish conscious report—produce more emergent but highly variable dynamic structure, indicating fragmented macroscopic organisation. Ketamine, which preserves dream-like states, shows reduced overall emergence but partial preservation of macroscopic structure similar to wakefulness. Regional brain contributions varied. The results reveal drug-specific reconfigurations of emergent dynamics, dissociate the amount of emergence from its organisation, and caution against equating emergence with consciousness level.

Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model

bioRxiv Preprint Server April 26, 2025 Rafael V. Lima Da Cruz, Rêmullo B. G. De Miranda Costa, Gabriel M. De Queiroz et al. 2 citations preprint

A single dose of the psychedelic DMT reversed depression-like behaviors and cognitive impairments in mice exposed to chronic stress, outperforming the standard antidepressant fluoxetine. When given during stress, DMT prevented anhedonia but not cognitive deficits. DMT remained effective even under anesthesia, suggesting its therapeutic action does not require the psychedelic experience. All DMT regimens increased the integration of adult-born granule cells in the brain and reduced abnormal cell integration. The findings position DMT as a promising rapid-acting antidepressant that works through structural brain repair.

Time-to-onset and temporal dynamics of EEG during breath-watching meditation

bioRxiv Preprint Server February 11, 2025 Saketh Malipeddi, Arun Sasidharan, Rahul Venugopal et al. 2 citations preprint

Meditation alters brain activity, particularly in alpha and theta frequency bands, but most research has focused on average power changes from rest to meditation rather than how quickly these changes emerge. This gap means little is known about the time-to-onset and temporal dynamics of neural shifts during meditation practice.

Ketamine reverses chronic stress-induced behavioral changes via Ca2+-permeable AMPA receptors in mice

bioRxiv Preprint Server October 7, 2024 Joshua C. Flowers, Paige E. Vetter, McKennon J. Wiles et al. 2 citations preprint

Chronic stress disrupts AMPA receptor signaling in the hippocampus, contributing to anxiety, depression, and cognitive decline. Low-dose ketamine rapidly increases GluA1-containing, GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs) in hippocampal neurons, enhancing glutamatergic synaptic strength and reducing anxiety- and depression-like behaviors in naïve animals. Ketamine may also protect against chronic stress effects, but whether CP-AMPARs mediate its antistress actions remains unknown.

Neural correlates of phenomenological attitude toward perceptual experience

bioRxiv Preprint Server July 7, 2024 Satoshi Nishida, Hiro Taiyo Hamada, Takuya Niikawa et al. 2 citations preprint

Shifting from the ordinary, outward-focused natural attitude to the reflective, inward-focused phenomenological attitude involves distinct neural processes. In a behavioral task alternating between these attitudes, participants made fewer errors but responded more slowly in the phenomenological attitude, indicating a difference beyond simple difficulty. Functional MRI revealed that multivoxel activation patterns in premotor cortex, posterior parietal cortex, supplementary motor area, and cerebellum could classify which attitude participants were in. Activation in these regions was lower during the phenomenological attitude, suggesting that this reflective stance suppresses action-related neural information. These findings offer initial evidence for the neural signature of the phenomenological attitude.

Electrophysiological correlates of lucid dreaming: sensor and source level signatures

bioRxiv Preprint Server April 9, 2024 Çağatay Demirel, Jarrod Gott, Kristoffer Appel et al. 2 citations preprint

Lucid dreaming, a state of conscious awareness during REM sleep, is associated with specific brain activity patterns. Compared to non-lucid REM sleep, EEG sensor-level differences were few. However, source-level analysis revealed increased gamma1 power (30-36 Hz) in left-hemispheric temporal areas during lucid dreaming, potentially reflecting verbal insight processes, and in right temporo-occipital regions including the precuneus around the onset of lucid eye signaling, linked to self-referential thinking. Beta power (12-30 Hz) decreased in right central and parietal areas including the temporo-parietal junction, possibly related to conscious reality assessment. Alpha-band (8-12 Hz) functional connectivity increased, contrasting with psychedelic states and highlighting enhanced self-awareness.

Awareness is determined by emotion and gender

bioRxiv Preprint Server February 27, 2024 Ema Jugović, Marta Poyo Solanas, Beatrice De Gelder 2 citations preprint

Threatening body expressions are more easily detected than fearful ones, especially by male participants viewing male stimuli. Awareness of emotional body images depends on the specific emotion expressed, the gender of the person in the image, and the gender of the viewer. Minimal awareness may be linked to emotion-specific features of body images. These findings highlight the role of affective factors in consciousness and the importance of gender differences in emotional processing.

Individual variability in neural representations of mind-wandering

bioRxiv Preprint Server January 20, 2024 Aaron Kucyi, Nathan Anderson, Tiara Bounyarith et al. 2 citations preprint

Mind-wandering, a common daily mental activity, varies uniquely from person to person. In three individuals who each reported hundreds of mind-wandering episodes during multiple fMRI sessions, reliable links between mind-wandering and default mode network (DMN) activation emerged when brain networks were analyzed within each person. However, the timing of spontaneous DMN activity relative to subjective reports, and the broader networks activated or deactivated during mind-wandering, differed across individuals. Whole-brain connectivity patterns that predicted mind-wandering within an individual did not fully generalize to others, and predictive models from larger datasets largely failed when applied to these densely-sampled individuals. This work demonstrates both conserved and variable neural representations of mind-wandering, highlighting the value of personalized approaches.

Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

bioRxiv Preprint Server June 8, 2023 Federica Lucantonio, Shuwen Li, Jaden Lu et al. 2 citations preprint

Ketamine rapidly alleviates anhedonia, a core symptom of depression involving loss of pleasure, but the underlying brain mechanisms were unclear. In mice subjected to chronic stress, a single dose of ketamine restored stress-induced weakening of excitatory synapses on specific neurons in the nucleus accumbens (NAc), a reward center. These neurons, called D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs), showed increased synaptic strength after ketamine. Artificially mimicking this change produced the same behavioral improvement, confirming its causal role. Ketamine acted on inputs from the medial prefrontal cortex and ventral hippocampus to NAc D1-MSNs, and blocking plasticity at these inputs prevented the behavioral effect. The findings demonstrate that ketamine rescues anhedonia through cell-type-specific and input-specific synaptic adaptations in the reward circuitry.

Ketamine evoked disruption of entorhinal and hippocampal spatial maps

bioRxiv Preprint Server February 5, 2023 Francis Kei Masuda, Yanjun Sun, Emily A Aery Jones et al. 2 citations preprint

Ketamine, used as a fast-acting anesthetic and antidepressant, causes spatial cognition side effects such as out-of-body experiences and spatial memory impairments, but the underlying neural mechanisms were unclear. In mice navigating virtual and real environments, ketamine acutely disrupted and then re-organized spatial representations in the medial entorhinal cortex, increasing excitatory neuron firing rates and degrading temporal coordination between cell pairs. In the hippocampus, neurons encoding the animal's position were suppressed after ketamine. These findings suggest that disruption of spatial coding in the entorhinal-hippocampal circuit may underlie ketamine-induced changes in spatial cognition.

Simple Neurofeedback via Machine Learning: Challenges in real time multivariate assessment of meditation state

bioRxiv Preprint Server September 27, 2022 Sruthi Susan Kuriakose, Aishwarya Swamy, Rahul Venugopal et al. 2 citations preprint

Meditation proficiency is hard to achieve without feedback because the mind easily wanders. EEG neurofeedback could help by providing real-time assessment. This work proposes a lightweight scheme using an autoencoder model trained on EEG features from long-term meditators. The model runs in real time on short data segments from a few channels, using reconstruction errors or latent variables as feedback parameters to measure meditation ability. However, results show that meditation states overlap substantially in multivariate EEG features and have prominent temporal dynamics, which simple one-class algorithms fail to capture. Multiple improvements to the autoencoder are described to address these issues and enable high-precision neurofeedback protocols.

Sex dependence of opioid-mediated responses to subanesthetic ketamine

bioRxiv Preprint Server September 6, 2022 Tommaso Di Ianni, Matine M. Azadian, Sedona N. Ewbank et al. 2 citations preprint

Ketamine rapidly reduces depressive symptoms in treatment-resistant depression, but its mechanisms are not fully understood. Recent clinical evidence controversially suggests that ketamine's efficacy may depend on opioid signaling. In rats, blocking opioid receptors suppressed ketamine-induced neurophysiologic changes in brain regions linked to depression and reward, but did not affect changes from a more selective NMDA receptor antagonist. This opioid-dependent response was strongly sex-dependent: absent in females and reversed by removing male gonads. Similar sex-dependent opioid effects appeared in ketamine-evoked structural plasticity and behavioral sensitization. These results indicate that ketamine may induce affective responses via opioid signaling, with subject sex as a strong influence, warranting direct assessment in future clinical trials.

Nonlinear EEG signatures of mind wandering during breath focus meditation

bioRxiv Preprint Server March 27, 2022 Yiqing Lu, Julio Rodriguez-Larios 2 citations preprint

During breath focus meditation, novice practitioners often experience mind wandering. Previous EEG studies using linear metrics have produced inconsistent results. This study assessed whether nonlinear EEG signatures could characterize mind wandering. Twenty-five participants were interrupted during meditation to report whether they were focusing on the breath or thinking about something else. EEG complexity was measured using three algorithms: Higuchi’s fractal dimension, Lempel-Ziv complexity, and sample entropy. EEG complexity was generally reduced during mind wandering compared to breath focus states. The authors conclude that EEG complexity metrics can distinguish mind wandering from breath focus in novice practitioners and could be used in future EEG neurofeedback protocols.

No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

bioRxiv Preprint Server December 2, 2021 Sean James Fallon 2 citations preprint

In a randomized double-blind, placebo-controlled study, three different low doses of LSD (5 μg, 10 μg, and 20 μg) were tested for their effects on working memory in a modified delay-match-to-sample task that required ignoring or updating novel items. There was no evidence that any of the LSD microdoses affected the accuracy or efficiency of working memory recall, nor was there evidence for differential effects on ignoring or updating. These results are preliminary due to the small sample size, and larger studies are required to establish whether LSD microdoses affect short-term recall.

Acute Ketamine Modulated Functional Brain Coupling and Dissociative and Affective States in Human Subjects: Interim Analyses

bioRxiv Preprint Server September 20, 2021 Laura M. Hack, Katherine G. Warthen, Xue Zhang et al. 2 citations preprint

Ketamine, a drug used for depression and anesthesia, causes dose-dependent increases in dissociation and intoxication, reduces emotional insensitivity, and raises stress as measured by cortisol. It alters brain connectivity, particularly between reward and negative affect circuits and thalamic sub-regions. Increased coupling between the amygdala and anteroventral thalamus correlates with greater dissociation and intoxication, while decreased coupling of anteromedial and posterior parietal thalamus correlates with increased sensory reward responsiveness. Drug-altered connectivity involving the nucleus accumbens and thalamic sub-regions shows negative associations with anxiety. These findings help disentangle the brain states underlying ketamine's acute effects, informing its therapeutic use and abuse risk.

Effects of Long-Term Meditation Practices on Sensorimotor Rhythm Based BCI Learning

bioRxiv Preprint Server September 9, 2020 Xiyuan Jiang, Emily Lopez, James Stieger et al. 2 citations preprint

Meditators outperformed non-meditators in brain-computer interface (BCI) cursor control tasks using motor imagery. Experienced meditators showed better performance in both 1-dimensional and 2-dimensional tasks, and fewer meditators were unable to generate decodable EEG signals. Meditators also had higher sensorimotor rhythm (SMR) predictor values and were better able to produce decodable EEG signals for SMR-based BCI control, suggesting meditation training may improve BCI performance.

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

bioRxiv Preprint Server May 5, 2020 Alexander D Shaw, Suresh D Muthukumaraswamy, Neeraj Saxena et al. 2 citations preprint

Ketamine alters brain oscillations, increasing high-frequency gamma waves and reducing low-frequency alpha and theta waves. A thalamo-cortical model better explained these changes than a cortex-only model. The model showed that ketamine increases specific synaptic connections: from superficial pyramidal cells to inhibitory interneurons via AMPA and NMDA receptors, and within-layer-5 pyramidal cell gain control via GABA-A and NMDA receptors. Receptor time-constants remained unchanged. These findings support using generative models to understand oscillatory data and provide computational evidence that ketamine alters local neural coupling through multiple neurotransmitter systems.

Studying the precuneus reveals structure-function-affect correlation in long-term meditators

bioRxiv Preprint Server October 30, 2019 Aviva Berkovich-Ohana, Edna Furman-Haran, Rafael Malach et al. 2 citations preprint

Meditation research has rarely examined how brain structure, function, and self-reports relate. This study demonstrates such a relationship for Mindfulness meditation (MM), which aims to reduce thought-related processes and enhance bodily awareness, thereby reducing identification with thought content and deconstructing maladaptive self-schema. The authors hypothesized that the structure of default mode network (DMN) regions, associated with spontaneous thoughts and self-representation, would negatively correlate with MM experience and self-reported positive affect, while positively correlating with DMN resting-state function.

The Electrophysiological Signature of Mind Wandering

bioRxiv Preprint Server October 25, 2019 Stefan Arnau, Christoph Löffler, Jan Rummel et al. 2 citations preprint

Mind wandering during tasks reduces accuracy and increases the risk of failure in both laboratory and real-world settings. EEG can measure mind wandering non-invasively, but prior findings on its neural correlates have been inconsistent. In a switching task with occasional thought probes, participants showed lower response accuracy when mind wandering. Alpha power during the inter-trial interval was significantly higher on trials where participants reported mind wandering, a widespread effect consistent with alpha power indicating an internally focused state. This suggests alpha power could be used to detect mind wandering online in critical tasks to prevent failures.

Consciousness as a Concrete Physical Phenomenon

bioRxiv Preprint Server June 4, 2019 Jussi Jylkkä, Henry Railo 2 citations preprint

The typical empirical approach to studying consciousness holds that we can only observe the neural correlates of experiences, not the experiences themselves. This paper argues, in contrast, that experiences are concrete physical phenomena that can causally interact with other phenomena, including observers, and therefore can be observed and scientifically modelled. The epistemic gap between an experience and a scientific model of its neural mechanisms stems from the fact that the model is a theoretical construct distinct from the concrete phenomenon it models, similar to any natural phenomenon and its model. A neuroscientific theory of the constitutive mechanisms of an experience is thus a model of the subjective experience itself, providing a solid basis for the empirical study of consciousness.

LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making

bioRxiv Preprint Server January 28, 2019 Thomas Pokorny, Patricia Duerler, Erich Seifritz et al. 2 citations preprint

A single dose of LSD (100 µg) impaired executive functions, cognitive flexibility, and spatial working memory in 25 healthy adults, but did not affect decision-making or risk-taking. These cognitive deficits were blocked by pretreatment with the 5-HT2A antagonist ketanserin (40 mg), indicating that the serotonin 2A receptor system is involved in specific cognitive processes. The findings suggest that blocking this receptor might help improve cognitive dysfunctions seen in psychiatric disorders.

Prevalence of near-death experiences and REM sleep intrusion in 1034 adults from 35 countries

bioRxiv Preprint Server January 28, 2019 Daniel Kondziella, Markus Harboe Olsen 2 citations preprint

About 10% of people report having had a near-death experience, according to a survey of 1,034 adults from 35 countries. Those who also experience REM sleep intrusion—when dream-like mental activity intrudes into waking life—are nearly three times more likely to report a near-death experience. The association held even after adjusting for age, gender, location, employment, and perceived threat. The authors suggest that brain physiology must be well preserved for such experiences to occur and be remembered, even when life is in danger.

The Hallucination Machine: A Deep-Dream VR platform for Studying the Phenomenology of Visual Hallucinations

bioRxiv Preprint Server November 3, 2017 Keisuke Suzuki, Warrick Roseboom, David J. Schwartzman et al. 2 citations preprint

A tool called the Hallucination Machine simulates visual hallucinatory experiences using deep convolutional neural networks and panoramic virtual reality videos of natural scenes. It induces visual phenomenology qualitatively similar to classical psychedelics, but does not evoke the temporal distortion commonly associated with altered states. This technique allows researchers to study altered consciousness without the confounding physiological and cognitive effects of psychoactive substances or psychopathological conditions, offering a valuable method for consciousness science and psychiatry.

Common Phenomenal and Neural Substrate Geometry in Visual Motion Perception

bioRxiv Preprint Server October 1, 2025 Kallum Robinson, Ariel Zeleznikow-Johnston, Jiahao Wu et al. 1 citation preprint

The qualitative aspects of consciousness (qualia) are difficult to study because they are subjective. This work takes a first step toward linking the structure of qualia to brain activity by comparing human dissimilarity ratings of visual motion experiences with neural population responses in mouse primary visual cortex. Human participants (N=171) rated dissimilarity of 48 visual motion stimuli. Mouse neural activity (n=751 neurons) was recorded from nine mice using optical imaging. Both human and mouse data showed structural commonalities: a categorical organization of stimulus direction best explained both structures. These commonalities were similar in awake and anaesthetized mice, suggesting coarse V1 geometry is relatively insensitive to this anesthesia. The authors note that future work combining behavior with causal intervention is needed to relate such neural structures to conscious experience.

Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA

bioRxiv Preprint Server July 3, 2025 Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al. 1 citation preprint

Psychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.