Damage to the primary visual cortex causes loss of conscious vision, yet some patients retain the ability to respond to stimuli despite reporting no visual experience. Why similar lesions produce such different behavioral phenotypes remains unclear. While research to date has focused primarily on spared pathways that bypass V1, here we asked whether these divergent outcomes are also linked to...
Abstract During wakefulness, we are used to perceive the environment through our senses, act on it and take these inputs to update our experiences and build the perceptions. When the inputs are not longer accurate or structured, people would sometimes have hallucinatory experiences. Whether such experiences are associated with distinct patterns of thought, and how they relate to large-scale...
Abstract Background Serotonergic psychedelics show promise for treating psychiatric disorders, with symptom improvements lasting for weeks after a single dose. Clarifying the neural basis of these effects would benefit from an identification of empirical biomarkers of such lasting shifts in brain function. Resting state EEG offers a rapid (<5 minute), low-cost window into functional brain...
Abstract Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type-specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed...
Abstract Identifying neural signatures of consciousness remains a central challenge in neuroscience. Sleep offers a tractable model for comparing brain activity in the presence or absence of subjective experience while minimizing behavioral responsiveness confounds. Using overnight 256-electrode high-density EEG in 140 participants and a serial-awakening paradigm, we analyzed 699 non-rapid eye...
Abstract Serotonergic psychedelics (SP) are increasingly used in clinical research and naturalistic settings, but their psychotic-like side effects, including persisting perceptual abnormalities (PPAs), are poorly understood. Psychosis-associated hallucinations are associated with susceptibility to conditioned hallucinations and computationally-estimated overweighting of perceptual...
Abstract Post-traumatic stress disorder (PTSD) is a highly prevalent, debilitating psychiatric condition. Existing treatments are ineffective for many patients. 3,4- methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has demonstrated substantial clinical efficacy but relies on prolonged, resource-intensive therapeutic protocols that limit scalability and accessibility. Here, we...
Abstract N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) are structurally related tryptamine psychedelics with emerging therapeutic potential, yet their comparative acute pharmacology and longer-term neuroplastic effects remain incompletely defined. Here we show that DMT produces a bell-shaped dose–response curve in the mouse head-twitch response (HTR) assay,...
ABSTRACT N,N -dimethyltryptamine (DMT) is an endogenous psychedelic tryptamine that has recently emerged as a promising therapeutic candidate for acute ischemic stroke. Although DMT consistently reduces infarct size, attenuates neuroinflammation, and improves functional outcome in experimental stroke, the cellular and receptor mechanisms underlying these effects remain poorly understood....
Abstract Psilocybin acutely alters neurotrophic, neurochemical, and immune markers, but the relationships between these responses and circulating microRNAs (miRNAs), i.e. non-coding RNAs that regulate post-transcriptional gene expression, remain unclear. In a randomized, double-blind, placebo-controlled study of 62 healthy adults who received psilocybin (0.17 mg/kg) or placebo, we previously...
Abstract Experiences in which the sense of the body becomes distorted offer a unique window into how the brain constructs the bodily self. Despite their clinical relevance in conditions such as depersonalization and body-image disorders, large-scale brain dynamics underlying unusual bodily experiences (UBEs) remain poorly understood, and no prior study has examined them systematically across...
Abstract Altered states of consciousness (ASC) refer to states that differ markedly from normal waking consciousness. ASC may occur spontaneously, such as in dreaming, or through consciousness modifying techniques, from meditation, to cannabis and psychedelics. The etymology behind the term psychedelic, meaning mind-manifesting, is based on the hypothesis that certain substances, including...
Abstract Background In acute disorders of consciousness following severe brain injury, the heterogeneity and multiplicity of brain lesions make it difficult to infer a direct causal link between lesion patterns and impaired consciousness. As a result, neuroimaging analyses performed in intensive care settings can inform theories of consciousness mainly through correlational, rather than causal,...
SUMMARY Psychedelics are powerful modulators of conscious perception, hypothesized to exert their effects by reorganizing large-scale brain functional connectivity. The circuit mechanisms underlying this reorganization remain unknown. Here, using widefield calcium imaging in awake mice, we found that the psychedelic DOI, in a 5-HT2A-dependent manner, acutely decreased the modularity of the...
SUMMARY How psychedelics act on cortical dendrites to produce long-lasting structural plasticity remains poorly understood. Here, we characterize the effects of psilocybin on dendritic calcium dynamics in pyramidal tract neurons of the mouse medial frontal cortex. Psilocybin transiently increases calcium event rates in apical dendritic tufts over a time course that parallels the drug’s...
Mental imagery is viewed as a fundamental component of human cognition, supporting memory, emotional processing, future simulation, and conscious experience. Although mental imagery vividness has traditionally been attributed to differences in sensory processing, emerging evidence suggests that internally generated images are also shaped by ongoing bodily and interoceptive signals. Here, we...
Underlying the very notion of choice is the fundamental idea of free-will, which is challenged by decision-neuroscience aiming to explain and predict choices using interactions of neurons. The question of whether any choice is truly a free-choice and born out of free-will has long been a subject of philosophical debate. In this work, we do not take a position on this debate, rather...
Neural avalanches - or threshold-defined bursts of coordinated activity - are traditionally characterised by scale-free statistics. However the study of their detailed spatiotemporal structure and their recurrence within spontaneous activity has been hindered by the variability of avalanches in duration and spatial extent. To tackle this challenge, we propose the use of flexible alignment: we...
Serotonergic psychedelics are advancing as psychiatric treatments, yet acute responses vary between individuals and the contribution of sex, a fundamental biological variable, remains largely unexamined. We pooled two double-blind, placebo-controlled studies in healthy volunteers (N = 72; 31 male, 41 female) comparing psilocybin 15 mg, 2C-B 20 mg, and LSD 50 μg. Linear mixed models tested sex...
Throughout the preclinical phase of Alzheimer's disease (AD) β-amyloid (Aβ) accumulates preferentially within the default mode network (DMN), yet the functional and behavioural consequences of this pathological burden remain poorly understood. Using task-based fMRI combined with Aβ, tau, and dopamine PET in cognitively normal older adults, we show that Aβ burden impairs learning independent of...
Nonduality is a foundational but conceptually elusive notion across several contemplative traditions. Nondual traditions challenge the assumption that a subject-object structure characteristic of ordinary experience is an intrinsic feature of conscious awareness. However, little remains known about the neurocognitive mechanisms associated with such experiential state. Here, we investigated how...
Abstract Serotonin (5-HT) 2A receptors (5-HT 2 AR) modulate corticolimbic circuits regulating fear extinction. Although activation of these receptors has been shown to facilitate fear extinction, the behavioral consequences of 5-HT 2 AR antagonism during extinction is not well defined. Here, we examined the systemic effects of two 5-HT 2 A receptor antagonists, the mixed 5-HT 2 A/ 2 C...
Abstract The use of meditation as a tool to improve human wellbeing is receiving considerable scientific interest. However, most existing research has focused on concentration-based practices. One powerful alternative is jhana meditation, which leads to states characterised by self-reinforcing bliss, potentially useful for a variety of clinical and scientific domains. However, our understanding...
Abstract Disorders of consciousness (DoC) are associated with large-scale alterations in brain dynamics, yet the structural factors that constrain these changes remain unclear. Here, we investigate how the topology of the structural connectome shapes the sensitivity of brain dynamics to perturbation using a whole-brain computational model constrained by diffusion MRI-derived connectivity. We...
Abstract Activation of mGluR2 (metabotropic glutamate receptor 2), the primary presynaptic autoreceptor for glutamate in the brain, is well established to attenuate the psychedelics-mediated behavioral and electrophysiological effects. However, the mechanisms responsible for these actions are controversial. The two competing mechanistic hypotheses have been proposed to explain this phenomenon...