Abstract Psychedelics profoundly alter conscious experience, yet how they reshape the relationship between brain anatomy and function remains unclear. In particular, it is unknown whether psychedelic states reflect a global disruption of structure–function organization or a frequency– and network-specific reconfiguration of neural dynamics relative to the structural connectome. Here we address...
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translational rodent model, we...
Abstract Visual hallucinations (VHs) occur across psychedelic states and diverse psychiatric and neurological conditions, yet their phenomenology remains difficult to characterise. Empirical research on VHs is hindered by the lack of large-scale phenomenological datasets, which limits both mechanistic accounts and the systematic characterisation of when and how they arise. Stroboscopic light...
Mind body practices like meditation and yoga, which are widely used to support mental health, involve paying attention to internal bodily sensations like the breath. During these practices, individuals often report "interoceptive lapses," moments when attention drifts away from the body. While lapses in attention to the external world have been widely studied, far less is known about...
Abstract Ketamine is an NMDA receptor antagonist with rapid-antidepressant properties when administered at a sub-anesthetic dose. Preclinical models indicate that a direct injection of ketamine into lateral habenula (Hb), a small midbrain structure with an evolutionarily preserved role in aversive learning across mammals, can rapidly relieve depression-like behavior. However, there is limited...
The mechanistic link between molecular pharmacology and global brain dynamics remains unresolved - a "scale bridge" problem central to consciousness research. We propose the Receptor-Constrained Dynamical Topology (RCDT) hypothesis: that the functional impact of neuromodulatory drugs propagates from local ligand-receptor binding events through spatially heterogeneous gain modulation to produce...
Abstract One of the most widely recognised neural correlates of consciousness, the P3b, has been challenged in recent years as a neural signal linked to conscious processing, due to its absence in no-report paradigms. Here, we test whether, even in the absence of a P3b, a period of late metastable brain activity may provide a more general signature of conscious access to perceptual information....
Abstract Lysergic acid diethylamide (LSD) profoundly alters conscious experience, yet the electrophysiological mechanisms by which it reshapes neural dynamics remain incompletely understood. A hallmark of psychedelic states is widespread cortical desynchronization, typically inferred from reductions in spectral power, but whether such effects reflect genuine weakening of neural oscillations or...
Abstract Mind-wandering (MW), the shift of attention away from an ongoing task, can be classified as either deliberate or spontaneous, depending on whether these internal thoughts arise intentionally or unintentionally. Previous functional magnetic resonance imaging-based resting state studies have shown that spontaneous MW traits are positively correlated with coupling within the default mode...
Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha–induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This suggests psilocybin can restore...
A main characteristic of biological systems is their capacity to dynamically adapt to environmental changes. In the brain, synaptic plasticity enables the strengthening or weakening of connections between neurons, allowing neural circuits to adapt based on experience, learning, and environmental changes. Yet, it is homeostatically regulated such that it avoids excessive proliferation of...
Abstract Production of the psychoactive compound psilocybin is a defining feature of the genus Psilocybe , commonly referred to as “psychedelic mushrooms”. However, Psilocybe fuscofulva is a striking exception within Psilocybe sensu stricto as it lacks the stereotypical blue bruising characteristic of the genus, and psilocybin has not been detected in the species.To investigate the evolutionary...
ABSTRACT Clinical trials suggest that a single dose of psilocybin is an effective treatment for substance use disorders (SUDs). Choice impulsivity is a value-based decision-making bias that predicts drug-intake escalation and is commonly associated with SUDs. The dorsomedial prefrontal cortex (dmPFC) regulates choice impulsivity and is enriched with 5-HT 2A receptors that mediate effects of...
Abstract Psilocybin is a classic psychedelic drug known to alter subjective experience and elicit long-term psychological changes, enhancing cognitive flexibility and reducing rigid self-related beliefs. Combined with compassion motivational primes that involve generating mental representations of compassion, it may increase the potential for activating the care-affiliative motivational...
Abstract With the resurgence of psychedelic research and the growing interest in their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological variable (SABV) on the...
Abstract Research into psychedelic compounds is in resurgence due to the exciting potential for their use in the treatment of psychiatric and mental health disorders. Despite this revival, remarkably little is known about their evolution. One of the most intriguing psychedelic compounds is psilocybin, the compound found in ‘magic’ mushrooms and used in ritual ceremonies in Central America for...
Abstract A leading theory for how psychedelics are able to produce robust clinical improvement and preclinical behavioral changes is that psychedelics act through neuroplastic mechanisms to induce lasting structural and functional alterations in neural circuits. However, psychedelics produce these effects across wide swaths of the brain. Based on our prior work, we hypothesized that engaging a...
Abstract Ayahuasca profoundly alters conscious experience, yet robust, time-resolved EEG markers of its network-level effects remain limited. We combined machine learning with complex-network analysis to quantify how functional connectivity reorganizes across time and hemispheres in resting-state EEG from a randomized, double-blind, placebo-controlled trial including three 5-min sessions:...
Abstract Classic serotonergic psychedelics are potent modulators of conscious awareness, yet the principles governing their effects on the temporal dynamics of brain activity remain unclear. Dominant theories propose that psychedelics increase the signal diversity and metastability of neural states, but whether this reflects a simple randomization of activity or a more structured reorganization...
Abstract 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...
Abstract Background Behavioural studies in animal models represent a critical component of psychiatric drug development. Positive results in animal studies have identified novel therapeutic targets for major depressive disorder (MDD) but efficacy in humans has largely not been borne out in clinical trials. A possible reason for this failed translation is inappropriate dose selection and the...
Abstract Psychedelics, particularly psilocybin, have shown therapeutic potential across several psychiatric conditions, including depression, anxiety, obsessive-compulsive disorder, and anorexia nervosa (AN). These disorders often share social deficits that may be effectively alleviated by psychedelics considering their use has been linked with emotional empathy and enhanced social cognition....
Abstract Background and Purpose Given the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we...
Abstract Evaluating consciousness levels after coma remains clinically challenging, and probing the brain’s functional hierarchy offers model-based biomarkers of brain states. We characterize the hierarchy loss in disorders of consciousness (DoC) via departures from non-equilibrium dynamics. Irreversible, directed interactions are indexed by deviation from the fluctuation– dissipation theorem...
Abstract Research on mental visual imagery typically relies on vividness ratings. However, vividness is ill-defined as it lacks an objective reference. Here, we present survey results that suggest vividness is nevertheless a robust measure. It explains individual differences of a broad range of subjective experiences, from the detail of mental imagery, the propensity to report having other...