Setting up a psychedelic study can be a long, arduous, and Kafkaesque process. Researchers are faced with a host of challenges in this rapidly evolving field, necessitating a range of considerations that remain largely unstandardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
Everyday cognition depends on the brain's capacity to shift between sensing the external world and constructing it from memory. To achieve this, large-scale cortical systems must flexibly integrate incoming sensory signals with internally generated representations. Here, we show that this flexibility is reflected in the macroscale architecture of the default mode network (DMN). Using convergent...
Abstract Background: Visual input is thought to influence spatial cognition and language. While blind individuals often rely on egocentric spatial representations, it remains unclear whether and how visual deprivation affects dream-related language. This study applied speech graph analysis (SGA) to investigate linguistic differences in dream reports from congenitally blind (CB), late blind...
Setting up a psychedelic study can be a long, arduous, and kafkaesque process. This rapidly-developing field poses several unique challenges for researchers, necessitating a range of considerations that have not yet been standardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
The default mode network (DMN) typically deactivates to external tasks, yet supports semantic cognition. It comprises medial temporal (MT), core, and frontotemporal (FT) subsystems, but its functional organization is unclear: the requirement for perceptual coupling versus decoupling, input modality (visual/verbal), type of information (social/spatial), and control demands all potentially affect...
Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers....
The default mode network (DMN) is a set of widely distributed brain regions in the parietal, temporal and frontal cortex. These regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition, many of which are linked to memory or abstract thought. Within the cortex, the DMN has been shown to be located in regions...
The glutamatergic modulator ketamine has been shown to rapidly reduce depressive symptoms in patients with treatment-resistant major depressive disorder (TRD). Although its mechanisms of action are not fully understood, changes in cortical excitation/inhibition (E/I) following ketamine administration are well documented in animal models and could represent a potential biomarker of treatment...
A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the...
When unoccupied by an explicit external task, humans engage in a wide range of different types of self-generated thinking. These are often unrelated to the immediate environment and have unique psychological features. Although contemporary perspectives on ongoing thought recognise the heterogeneity of these self-generated states, we lack both a clear understanding of how to classify the...
Lysergic acid diethylamide (LSD), the prototypical “psychedelic,” may be unique among psychoactive substances. In the decades that followed its discovery, the magnitude of its effect on science, the arts, and society was unprecedented. LSD produces profound, sometimes life-changing experiences in microgram doses, making it a particularly powerful scientific tool. Here we sought to examine its...
Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7...
When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in...
The concept of "emergence" has become commonplace in the modelling of complex systems, both natural and man-made; a functional property" emerges" from a system when it cannot be readily explained by the properties of the system's sub-units. A bewildering array of adaptive and sophisticated behaviours can be observed from large ensembles of elementary agents such as ant colonies, bird flocks or...
Under the predictive coding framework, perceptual learning and inference are dependent on the interaction between top-down predictions and bottom-up sensory signals both between and within regions in a network. However, how such feedback and feedforward connections are modulated in the state induced by lysergic acid diethylamide (LSD) is poorly understood. In this study, an auditory oddball...
RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with...
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for...
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we describe a simple model of spontaneous neural dynamics that controls an agent moving in a simple virtual environment. These dynamics generate interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics demonstrating the need for homeostatic...
Abstract Music is a highly dynamic stimulus, and consists of distinct acoustic features, such as pitch, rhythm and timbre. Neuroimaging studies highlight a hierarchy of brain networks involved in music perception. Psychedelic drugs such as lysergic acid diethylamide (LSD) temporary disintegrate the normal hierarchy of brain functioning, and produce profound subjective effects, including...
ABSTRACT Introduction: The question of how spatially-organized activity in the visual cortex behaves during eyes-closed, LSD-induced, visual psychedelic imagery has never been empirically addressed, although it has been proposed that under psychedelics the brain may function "as if" there is visual input when there is none (de Araujo, et al., 2012). We suspected that eyes-closed psychedelic...
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we explore a model of spontaneous neural dynamics and allow it to control a virtual agent moving in a simple environment. This setup generates interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics and suggest the need for homeostatic...
The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when...
Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally...
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in...
A variety of anatomical and physiological evidence suggests that the brain performs computations using motifs that are repeated across species, brain areas, and modalities. The computational architecture of cortex, for example, is very similar from one area to another and the types, arrangements, and connections of cortical neurons are highly stereotyped. This supports the idea that each...