Pharmacological agents that alter consciousness, including classic psychedelics and non-classic agents such as nitrous oxide, are known to affect multiple domains of conscious experience, including visual perception. While most neuroimaging studies rely on resting-state data to characterize altered states of consciousness, task-based approaches enable investigation of specific perceptual...
Understanding the relationship of conscious states to large-scale brain dynamics remains a central challenge in neuroscience. Here, diverse pharmacological and physiological perturbations-including psychedelics, sleep, and propofol sedation-are used to examine integration-segregation organization of brain networks across altered states of consciousness in humans using functional MRI. Across...
Information continuously flows between regions of the human brain, forming patterns that shift across states of consciousness, cognitive modes, and neuropsychiatric conditions. While functional magnetic resonance imaging (fMRI) reveals large-scale activity changes over seconds, the electrophysiological dynamics governing sub-second reconfiguration remain poorly understood. Here, relative phase...
Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform...
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...
Nitrous oxide (N2O) produces perceptual alterations and changes in large-scale brain network organization, yet its effects on task-specific visual processing remain unclear. Given the prominence of visual alterations during psychedelic exposure, we investigated how subanesthetic N2O modulates functional connectivity during visual stimulation. Thirteen healthy adults completed a...
Anesthesia has revolutionized surgical practice and offers a controlled model to study the neurobiology of consciousness. Functional magnetic resonance imaging (fMRI) studies have shown that anesthesia primarily disrupts connectivity across association cortices, suggesting that impaired integration between higher-order brain regions underlies unconsciousness. However, traditional fMRI paradigms...
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated for the treatment of psychiatric disorders. Although the neurophysiological effects of DMT in humans are well characterized, similar studies in animal models and data on the neurochemical effects of DMT are generally lacking, which are critical for a mechanistic understanding. Here, we combined behavioral...
Background Propofol exposure can produce heterogenous neural responses, from the expected suppression to transient paradoxical excitation. EEG measures of signal complexity and entropy have emerged as reliable markers of consciousness, but different types of complexity and entropy measures are often conflated. We used Type I and II complexity measures on the Complexity–Entropy Causal Plane...
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...
Structured Abstract Importance Ketamine has well known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Given prior studies that link specific cortical oscillations with specific therapeutic effects, it is likely that modulating selective aspects...
The preoptic area of the hypothalamus is key for the control of sleep onset and sleep homeostasis. Although traditionally considered exclusively somnogenic, recent studies identified a group of preoptic glutamatergic neurons that promote wakefulness. Specifically, our previous investigations demonstrated that chemogenetic stimulation of glutamatergic neurons within the medial-lateral preoptic...
Patients with refractory conditions often identify themselves with their illness, which affects multiple aspects of their lives. The pictorial representation of illness and self measure (PRISM) is a tool used to assess the enmeshment of individuals' perception of self with a particular medical condition, broadly termed self-condition enmeshment. This study aimed to evaluate changes in PRISM...
Background: Patients with refractory conditions often identify themselves with their illness, which affects multiple aspects of their lives. The pictorial representation of illness and self measure (PRISM) is a tool used to assess the enmeshment of individuals' perception of self with a particular medical condition, broadly termed self-condition enmeshment. Aims: This study aimed to evaluate...
Information continuously flows between regions of the human brain, exhibiting distinct patterns that dynamically shift across states of consciousness, cognitive modes, and neuropsychiatric conditions. In this study, we introduce Relative Phase Analysis (RPA), a method that leverages phase-lead/lag relationships to reveal the real-time dynamics of dominant directional patterns and their rapid...
Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in cortical networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on cortex-wide network dynamics. Previous electroencephalographic studies of psychedelics in rodents have primarily used sparse...
Introduction Fibromyalgia (FM) is the prototypical nociplastic pain condition, characterized by widespread pain and issues with cognition, mood, and sleep. Currently, there are limited treatment options available that effectively treat FM symptoms. Psilocybin-assisted therapy (PAT) is an emerging combined drug-therapy intervention, but no studies to-date have investigated PAT for FM. Methods...
Serotonergic psychedelics enhance neurophysiological complexity and the repertoire of brain states, whereas general anesthetics produce opposite effects. Serotonergic psychedelics are also known to increase wakefulness and reduce sleep time in rodents. Therefore, we hypothesized that 2,5-dimethoxy-4-iodopamphetamine (DOI), a serotonergic psychedelic, will reverse general anesthesia and restore...
Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: network efficiency (integration) and clustering (segregation). With this metric, we quantify brain state transitions from conscious wakefulness to unresponsiveness induced by the...
Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal...
Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic...
Accurate and generalizable classification of brain states is essential for understanding their neural underpinnings and improving clinical diagnostics. Traditionally, functional connectivity patterns and graph-theoretic metrics have been utilized. However, cortical gradient features, which reflect global brain organization, offer a complementary approach. We hypothesized that a machine learning...
The near-death experience has been reported since antiquity and is often characterized by the perception of light, interactions with other entities, and life recall. Near-death experiences can occur in a variety of situations, but they have been studied systematically after in-hospital cardiac arrest, with an incidence of 10 to 20%. Long attributed to metaphysical or supernatural causes, there...
Psychedelics, including N, N, Dimethyltryptamine (DMT), are being increasingly explored for therapeutic potential to treat psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. These and other psychiatric conditions have a bidirectional relationship with sleep patterns but the impact of psychedelics, particularly DMT, on sleep architecture is incompletely...
Consciousness requires a dynamic balance of integration and segregation in functional brain networks. An optimal integration-segregation balance depends on two key aspects of functional connectivity: global efficiency (i.e., integration) and clustering (i.e., segregation). We developed a new fMRI-based measure, termed the integration-segregation difference (ISD), which captures both aspects. We...