Frontiers in Human Neuroscience
January 1, 2014
Robin Carhart‐Harris, Robert Leech, Peter J. Hellyer et al.
1,289 citations
Entropy, a measure of uncertainty or disorder, is applied to brain function and consciousness, focusing on the psychedelic state induced by psilocybin. The psychedelic state is considered a primary or primitive state of consciousness, characterized by elevated entropy in brain function, including a greater repertoire of functional connectivity motifs that form and fragment over time. This suggests primary states may exhibit criticality, a transition zone between order and disorder. Normal waking consciousness suppresses entropy, operating just below criticality, which constrains cognition and enables metacognitive functions like reality-testing and self-awareness. Entry into primary states involves collapse of default-mode network activity and decoupling from medial temporal lobes. These hypotheses can be tested by comparing brain activity in REM sleep, early psychosis, normal waking consciousness, and anesthesia.
Proceedings of the National Academy of Sciences
January 23, 2012
Alessandro Colasanti, Robin J. Tyacke, Robert Leech et al.
1,191 citations
Psychedelic drugs like psilocybin, found in magic mushrooms, produce profound changes in consciousness by decreasing activity and connectivity in key brain hub regions. Using functional MRI, researchers observed that psilocybin reduced cerebral blood flow and BOLD signal, especially in the thalamus, anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). Decreased activity in the ACC and medial prefrontal cortex (mPFC) predicted the intensity of subjective psychedelic effects. Psilocybin also reduced positive coupling between the mPFC and PCC. These findings suggest that psychedelics work by dampening the brain's connector hubs, leading to a state of unconstrained cognition.
Nature reviews. Neuroscience
July 5, 2021
Jonathan Smallwood, Boris C. Bernhardt, Robert Leech et al.
970 citations
The default mode network (DMN) is a set of brain regions in the parietal, temporal, and frontal cortex that typically reduce activity during attention-demanding tasks but increase activity during complex cognition linked to memory or abstract thought. These regions are located farthest from sensory and motor systems. The paper considers how knowledge of the DMN's topographic characteristics can be used to better understand its contributions to cognition and behavior.
Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
Journal of Neuroscience
March 2, 2011
Robert Leech, Salwa Kamourieh, Christian F. Beckmann et al.
801 citations
The posterior cingulate cortex (PCC), a core region of the default mode network (DMN), shows distinct roles in attention depending on its dorsal and ventral parts. Using fMRI during a working-memory task, standard subtraction analysis showed overall deactivation with increasing difficulty. However, dual-regression functional connectivity revealed a dissociation: the ventral PCC reduced integration with the DMN and anticorrelation with the cognitive control network (CCN) as task demands rose, while the dorsal PCC increased DMN integration and anticorrelation with the CCN. At rest, the dorsal PCC connected with both DMN and attentional networks. These results indicate the PCC supports internally directed thought at low demands and that the dorsal PCC modulates dynamic interactions between networks for attention allocation.
Sci Rep
October 13, 2017
Robin L Carhart-Harris, Leor Roseman, Mark Bolstridge et al.
590 citations
In patients with treatment-resistant depression, a single dose of psilocybin combined with psychological support reduced depressive symptoms and altered brain activity and connectivity. Functional MRI scans before and after treatment showed decreased blood flow in the temporal cortex, including the amygdala, and increased resting-state functional connectivity within the default-mode network. Reduced amygdala blood flow correlated with fewer depressive symptoms. Changes in connectivity between the ventromedial prefrontal cortex and inferior lateral parietal cortex, as well as between the parahippocampus and prefrontal cortex, predicted treatment response at five weeks. These brain changes differ from the drug's acute effects and suggest a 'reset' of neural circuits.
Curr Biol
April 13, 2016
Enzo Tagliazucchi, Leor Roseman, Mendel Kaelen et al.
531 citations
LSD, a potent serotonin-receptor agonist, increases global functional connectivity in the human brain, particularly in high-level association cortices and the thalamus, as shown by fMRI. These effects overlap with serotonin 2A receptor densities and correlate with subjective reports of ego dissolution. The drug also enhances communication between normally distinct brain networks, reducing the brain's modular and rich-club organization. This is the first modern human imaging study of LSD's acute effects on brain connectivity, demonstrating that LSD selectively expands global connectivity and blurs perceptual boundaries between self and environment.
Human Brain Mapping
July 3, 2014
Enzo Tagliazucchi, Robin Carhart‐Harris, Robert Leech et al.
423 citations
Psilocybin, the active compound in magic mushrooms, increases the variability and range of brain activity and connectivity. Using fMRI, fifteen healthy volunteers were scanned before, during, and after receiving psilocybin or a placebo. Psilocybin raised the variability of blood-oxygen-level-dependent signals in the hippocampi and anterior cingulate cortex. Changes in the spectral behavior of brain signals were limited to higher-order networks, including the default mode, executive control, and dorsal attention networks. The brain also explored a wider repertoire of connectivity states after psilocybin than under control conditions. These findings help explain the unconstrained, hyper-associative quality of consciousness in the psychedelic state.
Sci Rep
November 19, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
325 citations
Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.
Frontiers in Human Neuroscience
May 27, 2014
Leor Roseman, Robert Leech, Amanda Feilding et al.
293 citations
Psychedelic drugs like psilocybin and MDMA perturb consciousness in distinct ways, offering a tool to study brain mechanisms underlying conscious states. In placebo-controlled studies, psilocybin increased resting-state functional connectivity between brain networks, making them less differentiated, while decreasing connectivity between visual and sensorimotor networks. MDMA produced less marked changes in between-network connectivity, suggesting that the extensive network alterations under psilocybin may be unique to classic psychedelics and relate to their profound effects on consciousness. This analytical approach could help characterize other altered conscious states.
Schizophrenia Bulletin
October 6, 2012
Robin Carhart‐Harris, Robert Leech, David Erritzøe et al.
267 citations
Psilocybin, a classic psychedelic, increases functional connectivity between the default-mode network (DMN) and task-positive network (TPN), reducing the normal orthogonality between these networks. In 15 healthy volunteers, intravenous psilocybin (vs placebo) during resting-state fMRI scans led to greater DMN-TPN connectivity, a pattern also seen in psychosis and meditative states. Thalamocortical connectivity remained unchanged, suggesting it relates to arousal rather than the separateness of internal versus external focus. The findings support psilocybin as a model for early psychosis, where compromised DMN-TPN orthogonality may explain phenomenological overlaps.
The British Journal of Psychiatry
January 27, 2012
Robin Carhart‐Harris, Robert Leech, Tom A. Williams et al.
241 citations
Psilocybin, a classic psychedelic drug, may enhance the vividness and visual imagery of positive autobiographical memories. In a small study of ten healthy participants, functional magnetic resonance imaging scans showed that under psilocybin, compared to placebo, recollection of positive memories produced additional visual and sensory cortical activations in the late phase of recall. Participants also rated memories as more vivid and visually rich after psilocybin, and higher vividness correlated with greater subjective wellbeing at follow-up. These findings suggest psilocybin could be useful in psychotherapy for facilitating recall of salient memories or reversing negative cognitive biases.
Journal of Neuroscience
January 8, 2014
Peter J. Hellyer, Murray Shanahan, Gregory Scott et al.
225 citations
During an attentionally demanding task, brain activity becomes more synchronized and less variable over time compared to rest. This shift is linked to increased activity in the frontoparietal control/dorsal attention network and decreased activity in the default mode network. A computational model confirmed that activating the frontoparietal network increases synchrony and reduces variability, while activating the default mode network does the opposite. The balance between these networks may control how the brain shifts between an unfocused, exploratory state with high variability and a focused, constrained state with low variability.
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Biological Psychiatry
January 10, 2014
Robin Carhart‐Harris, Kevin Murphy, Robert Leech et al.
182 citations
The medial temporal lobes (MTLs) are specifically involved in how MDMA works in the brain, though more research is needed to understand how the drug's characteristic subjective effects emerge from its modulation of spontaneous brain activity.
iScience
February 2, 2021
Jonathan Smallwood, Adam Turnbull, Hao-ting Wang et al.
130 citations
The landscape of ongoing thought is heterogeneous and shaped by both personal traits and environmental context. Recent work shows that attention and control systems organize experience in response to changing demands, while the default mode network contributes not only to task-negative or episodic content but also to the vividness of experience in both task contexts and spontaneous self-generated states. Multiple neural systems reflect the landscape of ongoing thought, and it is important to distinguish processes that shape how experience unfolds from those that regulate it.
Neuropharmacology
November 20, 2017
Christopher Timmermann, Meg J. Spriggs, Mendel Kaelen et al.
83 citations
LSD reduces the brain's automatic neural adaptation to familiar sounds and blunts the neural 'surprise' response to unexpected sounds. Using magnetoencephalography and dynamic causal modeling, the authors found that LSD modulates backward (top-down) connectivity within a fronto-temporal network and intrinsic connectivity in the primary auditory cortex. These patterns resemble those seen in schizophrenia, ketamine states, and reduced consciousness, suggesting that backward connectivity may reflect altered perceptual learning common to multiple altered states rather than a direct marker of conscious level. The findings challenge top-down hypotheses of consciousness and indicate that several altered states may share this biophysical mechanism.
Scientific Reports
December 3, 2020
Theodoros Karapanagiotidis, Diego Vidaurre, Andrew J. Quinn et al.
82 citations
When people are not engaged in an explicit task, they experience a variety of self-generated thoughts, such as planning or reminiscing. Using machine learning to analyze brain activity from resting-state fMRI scans, researchers identified distinct neural states that recur over time. Two of these states predicted different patterns of thinking. One neural state, resembling activity seen during demanding tasks, was linked to problem-solving about the future. Another state, associated with less demanding conditions, was tied to intrusive thoughts about the past. These two states fell at opposite ends of a brain hierarchy related to cognitive demand. The findings show that tracking moment-to-moment changes in brain function can help classify self-generated mental states and that these states align with the brain's response to cognitive tasks.
Neuroscience & Biobehavioral Reviews
May 5, 2015
Federico Turkheimer, Robert Leech, Paul Expert et al.
64 citations
The brain appears to use repeated computational building blocks—canonical computational motifs—that are similar across species, brain areas, and sensory modalities. These motifs, grounded in stereotyped neuronal circuits and inhibitory interneurons, operate at micro-, meso-, and macro-scales to form a multiplexing information system capable of encoding and transmitting increasingly complex information. Similar activation patterns are observed in primary sensory cortices via electrophysiology and in large-scale networks measured with fMRI. The authors apply this canonical model to unify evidence on the pathophysiology of schizophrenia and suggest it may extend to other brain disorders involving GABA interneuron dysfunction.
Hum Brain Mapp
April 29, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
63 citations
Under LSD, with eyes closed, patches of the visual cortex that represent the same part of the visual field (e.g., both representing the horizontal meridian) showed stronger functional connectivity than patches representing different parts, compared to placebo. This pattern, measured in 10 healthy subjects using resting-state fMRI, suggests that the early visual system during LSD-induced imagery behaves as if it were processing actual visual input, even when no external visual stimuli are present.
PLoS Computational Biology
August 24, 2017
Peter J. Hellyer, Claudia Clopath, Angie A. Kehagia et al.
21 citations
A simple computational model of spontaneous neural dynamics controlling an agent in a virtual environment shows that brain-environment feedback can rapidly destabilize neural and behavioral dynamics, requiring homeostatic mechanisms. Local homeostatic plasticity, where inhibition adjusts to balance excitation, and global mechanisms, where regional task-negative activity compensates for task-positive sensory input in another region, both stabilize behavior. The results suggest complementary functional roles for local and macroscale homeostatic processes and propose a novel function for macroscopic task-negative activity patterns, such as the default mode network, in maintaining stable neural and behavioral dynamics.
Journal of Neuroscience
April 8, 2024
Ximing Shao, Katya Krieger‐Redwood, Meichao Zhang et al.
20 citations
The default mode network (DMN) typically deactivates during external tasks but supports semantic cognition. Analysis of four human fMRI datasets shows that its subsystems respond differently: the frontotemporal subsystem activates across domains and modalities, especially during abstract verbal tasks, and shows more tuned states with higher semantic retrieval demands. The medial temporal subsystem activates for both perceptually coupled scenes and decoupled autobiographical memory, with stronger responses to picture associations, supporting scene construction. The core DMN consistently deactivates, particularly for externally oriented tasks. These distinct responses relate to each subsystem's location on intrinsic connectivity gradients, revealing complementary roles in semantic cognition.
bioRxiv (Cold Spring Harbor Laboratory)
June 25, 2017
Mendel Kaelen, Romy Lorenz, Frederick S. Barrett et al.
20 citations
preprint
Lysergic acid diethylamide (LSD) alters how the brain processes music, particularly by enhancing activity and connectivity in networks linked to music perception and emotion. Sixteen healthy volunteers listened to a 7-minute music piece during fMRI after taking either 75 mcg of LSD or a placebo. The acoustic feature of timbral complexity—the richness of the music's spectral distribution—drove the most pronounced changes in brain activity and connectivity under LSD. These changes correlated with increased feelings of wonder evoked by the music. The results suggest a neurobiological basis for why music is useful in psychedelic therapy.
bioRxiv
July 18, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
Journal of Vision
September 1, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
4 citations
Under LSD, the visual cortex's resting-state functional connectivity (RSFC) becomes more dependent on its intrinsic retinotopic organization, as if the brain were processing actual visual input despite closed eyes. In 10 healthy subjects, RSFC between non-adjacent patches of V1 and V3 that represent congruent parts of the visual field (both horizontal or both vertical meridians) was significantly stronger than connectivity between incongruent patches (horizontal-vertical), compared to placebo. The difference between congruent and incongruent connectivity was greater under LSD (Cohen's d=1.6), suggesting that psychedelic imagery involves transient local retinotopic activation similar to that from visual stimulation.