Publications
239 results found
Petri G, Expert P, Turkheimer F, et al., 2014, Homological scaffolds of brain functional networks, Journal of the Royal Society Interface, Vol: 11, ISSN: 1742-5689
Networks, as efficient representations of complex systems, have appealed toscientists for a long time and now permeate many areas of science, includingneuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198.(doi:10.1038/nrn2618)). Traditionally, the structure of complex networks hasbeen studied through their statistical properties and metrics concerned withnode and link properties, e.g. degree-distribution, node centrality and modularity.Here, we study the characteristics of functional brain networks at themesoscopic level from a novel perspective that highlights the role of inhomogeneitiesin the fabric of functional connections. This can be done by focusingon the features of a set of topological objects—homological cycles—associatedwith the weighted functional network. We leverage the detected topologicalinformation to define the homological scaffolds, a new set of objects designed torepresent compactly the homological features of the correlation network andsimultaneously make their homological properties amenable to networks theoreticalmethods. As a proof of principle, we apply these tools to compare restingstatefunctional brain activity in 15 healthy volunteers after intravenous infusionof placebo and psilocybin—the main psychoactive component of magic mushrooms.The results show that the homological structure of the brain’s functionalpatterns undergoes a dramatic change post-psilocybin, characterized by theappearance of many transient structures of low stability and of a smallnumber of persistent ones that are not observed in the case of placebo.
Tagliazucchi E, Carhart-Harris R, Leech R, et al., 2014, Enhanced Repertoire of Brain Dynamical States During the Psychedelic Experience, HUMAN BRAIN MAPPING, Vol: 35, Pages: 5442-5456, ISSN: 1065-9471
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- Citations: 198
Carhart-Harris R, Kaelen M, Nutt D, 2014, How do hallucinogens work on the brain?, PSYCHOLOGIST, Vol: 27, Pages: 662-665, ISSN: 0952-8229
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- Citations: 12
Leech R, Scott G, Carhart-Harris R, et al., 2014, Spatial Dependencies between Large-Scale Brain Networks, PLoS ONE, Vol: 9
<p>Functional neuroimaging reveals both increases (task-positive) and decreases (task-negative) in neural activation with many tasks. Many studies show a <italic>temporal</italic> relationship between task positive and task negative networks that is important for efficient cognitive functioning. Here we provide evidence for a <italic>spatial</italic> relationship between task positive and negative networks. There are strong spatial similarities between many reported task negative brain networks, termed the default mode network, which is typically assumed to be a spatially fixed network. However, this is not the case. The spatial structure of the DMN varies depending on what specific task is being performed. We test whether there is a fundamental <italic>spatial</italic> relationship between task positive and negative networks. Specifically, we hypothesize that the distance between task positive and negative voxels is consistent despite different spatial patterns of activation and deactivation evoked by different cognitive tasks. We show significantly reduced variability in the distance between within-condition task positive and task negative voxels than across-condition distances for four different sensory, motor and cognitive tasks - implying that deactivation patterns are spatially dependent on activation patterns (and <italic>vice versa</italic>), and that both are modulated by specific task demands. We also show a similar relationship between positively and negatively correlated networks from a third ‘rest’ dataset, in the absence of a specific task. We propose that this spatial relationship may be the macroscopic analogue of microscopic neuronal organization reported in sensory cortical systems, and that this organization may reflect homeostatic plasticity necessary for efficient brain function.</p>
Roseman L, Leech R, Feilding A, et al., 2014, The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers, Frontiers in Human Neuroscience, Vol: 8, ISSN: 1662-5161
Carhart-Harris R, Nutt D, 2014, Was it a vision or a waking dream?, FRONTIERS IN PSYCHOLOGY, Vol: 5, ISSN: 1664-1078
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- Citations: 21
Carhart-Harris RL, Wall MB, Erritzoe D, et al., 2014, The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 17, Pages: 527-540, ISSN: 1461-1457
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- Citations: 59
Carhart-Harris RL, Leech R, Hellyer PJ, et al., 2014, The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs, Frontiers in Human Neuroscience, Vol: 8, Pages: 1-22, ISSN: 1662-5161
Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early ps
Turton SP, Nutt DJ, Carhart-Harris RL, 2014, A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment., Curr Drug Abuse Rev, Vol: 7, Pages: 117-127, ISSN: 1874-4737
Background: This report documents the phenomenology of the subjective experiences of 15 healthy psychedelic experienced volunteers who were involved in a functional magnetic resonance imaging (fMRI) study that was designed to image the brain effects of intravenous psilocybin. Methods: The participants underwent a semi-structured interview exploring the effects of psilocybin in the MRI scanner. These interviews were analysed by Interpretative Phenomenological Analysis. The resultant data is ordered in a detailed matrix, and presented in this paper. Results: Nine broad categories of phenomenology were identified in the phenomenological analysis of the experience; perceptual changes including visual, auditory and somatosensory distortions, cognitive changes, changes in mood, effects of memory, spiritual or mystical type experiences, aspects relating to the scanner and research environment, comparisons with other experiences, the intensity and onset of effects, and individual interpretation of the experience. Discussion: This article documents the phenomenology of psilocybin when given in a novel manner (intravenous injection) and setting (an MRI scanner). The findings of the analysis are consistent with previous published work regarding the subjective effects of psilocybin. There is much scope for further research investigating the phenomena identified in this paper.
Carhart-Harris RL, Leech R, Erritzoe D, et al., 2013, Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis, SCHIZOPHRENIA BULLETIN, Vol: 39, Pages: 1343-1351, ISSN: 0586-7614
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- Citations: 135
Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, et al., 2013, Broadband Cortical Desynchronization Underlies the Human Psychedelic State, JOURNAL OF NEUROSCIENCE, Vol: 33, Pages: 15171-15183, ISSN: 0270-6474
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- Citations: 255
Carhart-Harris RL, Nutt DJ, 2013, Experienced Drug Users Assess the Relative Harms and Benefits of Drugs: A Web-Based Survey, JOURNAL OF PSYCHOACTIVE DRUGS, Vol: 45, Pages: 322-328, ISSN: 0279-1072
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- Citations: 30
Carhart-Harris RL, Brugger S, Nutt DJ, et al., 2013, Psychiatry's next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 27, Pages: 771-778, ISSN: 0269-8811
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- Citations: 30
Carhart-Harris R, 2013, Psychedelic drugs, magical thinking and psychosis., J Neurol Neurosurg Psychiatry, Vol: 84
After completing an undergraduate degree in Psychology in 2003, Robin studied psychoanalysis at Masters level, receiving his MA in 2004. In 2005, Robin began a four year PhD in Psychopharmacology at the University of Bristol. Working for Professor David Nutt and Dr Sue Wilson, Robin's thesis focused on sleep and serotonin function in ecstasy users. Robin conducted a clinical study involving sleep electroencephalography (EEG) and tryptophan depletion. In 2009, working closely with the Beckley Foundation, he successfully coordinated the first clinical study of psilocybin in the UK and the first clinical study of a classic psychedelic drug in the UK for over 40 years. Also in 2009, Robin moved to Imperial College London to continue his work under the supervision of Professor David Nutt. With the collaboration of Professor Richard Wise at Cardiff University, Robin has since coordinated the first resting state fMRI investigation of a classic psychedelic drug and the first fMRI and PET investigations of psilocybin and MDMA. Robin is first author on a number of publications in peer-reviewed scientific journals including review articles with eminent neuroscientists Professor's Helen Mayberg and Karl Friston. He has presented his data at several international conferences and has appeared on BBC News.
Carhart-Harris R, 2013, Is the brainstem really sufficient for a consciousness that would have interested freud?, Neuropsychoanalysis, Vol: 15, Pages: 29-32, ISSN: 1529-4145
This is an interesting Target Article from Mark Solms, and I am grateful for having been asked to comment on it. However, I have to disagree with some of its main arguments—for exle, that the brainstem is sufficient for a form of consciousness that is relevant to the Freudian model of the mind (which depends on the notion of conflict between the ego and the id), and that the id can be associated with the upper brainstem, and the ego with the cortex. I have argued that these ideas seem too crude and are lacking in a sufficient evidence base. © 2013, Taylor & Francis Group, LLC. All rights reserved.
Turton S, Carhart-Harris R, Fielding A, et al., 2012, Intravenously Administered Psilocybin in the fMRI environment - a phenomenological analysis, British Association for Psychopharmacology Summer Meeting
Introduction: This study aimed to investigate the phenomenology of the perceptual changes caused by the psychedelic agent psilocybin (found in ‘magic mushrooms’)when administered intravenously in a magnetic resonance imaging (MRI) scanner. The subjective effects of psilocybin have been previously documented (Pahnke, 1969,Int Psychiatry Clin 5(4):149-62, Studerus et al, 2011, J Psychopharmacol 25(11):1434-52) however, this provides an opportunity to investigate the effects when psilocybinis administered in a novel manner (intravenous injection) and setting (MRI scanner). Methods: Fifteen healthy volunteers enrolled in a study investigating the brain effectsof intravenous psilocybin using functional MRI (fMRI) imaging (Carhart-Harris et al. 2012, Proc Natl Acad Sci, 109(6):2138-2143). The study consisted of one placeboscan and a second scan during which 2mg of psilocybin were administered intravenously. Following the second fMRI scan participants underwent a semi-structuredinterview, allowing them to describe and elaborate on their experience. These interviews were fi lmed and the content analysed using an interpretative phenomenologicalanalysis methodology. Results: The peak effects of psilocybin lasted between 15-30 minutes. The two phenomenological categories that arose from the analysis consistedof experiences related to the fMRI scanner and the research environment, and experiences related to the perceptual changes caused by the psilocybin. Key componentsrelating to the scanner environment were: the scanner having a negative effect on the experience (n=11), the research environment having a negative effect on theexperience (n=11) diffi culty with the scanner noise (n=10), sense of sensory deprivation (n=8) and preferring a more ‘natural’ environment (n=9). Components relatingto the perceptual changes included visual hallucinations or distortions (n=15), physical sensations (n=12), auditory distortions (n=7), altered time perception (n=13)
Carhart-Harris RL, Leech R, Williams TM, et al., 2012, Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin, BRITISH JOURNAL OF PSYCHIATRY, Vol: 200, Pages: 238-244, ISSN: 0007-1250
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- Citations: 125
Carhart-Harris RL, Erritzoe DE, Williams TM, et al., 2012, The neural correlates of the psychedelic state as determined by fMRI studies with psilocybin, Proceedings of the National Academy of Sciences of USA
Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about howthey work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normalwaking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen leveldependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.
Carhart-Harris RL, Williams TM, Sessa B, et al., 2011, The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 25, Pages: 1562-1567, ISSN: 0269-8811
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- Citations: 30
Carhart-Harris RL, King LA, Nutt DJ, 2011, A web-based survey on mephedrone, DRUG AND ALCOHOL DEPENDENCE, Vol: 118, Pages: 19-22, ISSN: 0376-8716
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- Citations: 152
Carhart-Harris R, Erritzoe D, Stone J, et al., 2011, The functional brain correlates of the psychedelic state: an arterial spin labelling study with psilocybin, 24th Congress Meeting of European-College-of-Neuropsychopharmacology, Publisher: ELSEVIER SCIENCE BV, Pages: S313-S313, ISSN: 0924-977X
Carhart-Harris RL, Erritzoe DE, Williams TM, et al., 2011, DECREASED CEREBRAL BLOOD FLOW AFTER INTRAVENOUS PSILOCYBIN, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A39-A39, ISSN: 0269-8811
Carhart-Harris RL, Williams TM, Sessa B, et al., 2010, THE ADMINISTRATION OF PSILOCYBIN TO HEALTHY HALLUCINOGEN-EXPERIENCED VOLUNTEERS IN A MOCK-FMRI ENVIRONMENT: A PRELIMINARY INVESTIGATION OF TOLERABILITY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A60-A60, ISSN: 0269-8811
Carhart-Harris RL, Nutt DJ, 2010, User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study, Journal of Substance Use: for nursing, health and social care, Vol: 15, Pages: 283-300, ISSN: 1357-5007
This study used a web-based questionnaire to investigate user perceptions of the benefits and harms of hallucinogenic drug use. Over 600 forms were submitted. Users were asked to comment on the acute and prolonged effects of different drugs and to provide more specific information on how particular drugs have harmed and/or helped them. Subjects reported relatively less harm associated with the classic hallucinogens, LSD and psilocybin, than other drugs specifically focused on in the questionnaire (MDMA, cannabis, ketamine and alcohol). A wide-range of benefits was reported, including: help with mood disorders, addictions and migraine as well as more general long-term improvements in wellbeing. Symptoms of hallucinogen persisting perceptual disorder were reported by a number of subjects and these were most closely associated with use of LSD; however, few users regarded these effects as troubling. Eighty-one per cent of users reported having had a ‘spiritual experience’ on a hallucinogenic drug and over 90% considered ‘access to the unconscious mind’ to be a specific property of the classic hallucinogens. With caution, these findings support recent calls for a systematic investigation of the therapeutic potential of the classic hallucinogens and highlight the scope for empirical investigations of spiritual and psychodynamic phenomena.
Carhart-Harris RL, Friston KJ, 2010, The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas, BRAIN, Vol: 133, Pages: 1265-1283, ISSN: 0006-8950
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- Citations: 265
Carhart-Harris RL, Nutt DJ, Munafo MR, et al., 2009, Equivalent effects of acute tryptophan depletion on REM sleep in ecstasy users and controls, Psychopharmacology (Berl), Vol: 206, Pages: 187-196
INTRODUCTION: This study sought to test the association between 3,4-methylenedioxymethamphetamine use, serotonergic function and sleep. MATERIALS AND METHODS: Ambulatory polysomnography was used to measure three nights sleep in 12 ecstasy users and 12 controls after screening (no intervention), a tryptophan-free amino acid mixture (acute tryptophan depletion (ATD)) and a tryptophan-supplemented control mixture. RESULTS: ATD significantly decreased rapid eye movement (REM) sleep onset latency, increased the amount of REM sleep and increased the amount of stage 2 sleep in the first 3 h of sleep. There was no difference between ecstasy users' and controls' sleep on the screening night or after ATD. DISCUSSION: These findings imply that the ecstasy users had not suffered significant serotonergic damage as indexed by sleep
Carhart-Harris RL, Nutt DJ, Munafo M, et al., 2009, Current and former ecstasy users report different sleep to matched controls: a web-based questionnaire study, J.Psychopharmacol., Vol: 23, Pages: 249-257
This study sought to test the association between ecstasy-use and abnormal sleep. An anonymous web-based questionnaire containing questions on drug use and sleep was completed by 1035 individuals. From this large sample, a group of 89 ecstasy users were found who reported very little use of other drugs. This "ecstasy-only" group was further divided into two groups of 31 current users and 58 abstinent users. The subjective sleep of current and former ecstasy-only users was compared with that of matched controls. Patients were asked to rate their sleep according to: 1) sleep quality, 2) sleep latency, 3) night time awakenings and 4) total sleep time. Current ecstasy-only users reported significantly worse sleep quality (P < 0.05) and a greater total sleep time (P < 0.001) than controls. It was inferred that these differences might be due to recovery from the acute effects of the drug. Abstinent ecstasy-only users reported significantly more nighttime awakenings than controls (P < 0.01). These subjective findings are in agreement with the objective findings of previous studies showing persistent sleep abnormalities in ecstasy users
Carhart-Harris RL, Mayberg HS, Malizia AL, et al., 2008, Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry., Ann Gen Psychiatry, Vol: 7
Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities.
Harris RC, 2007, Waves of the unconscious: The neurophysiology of dreamlike phenomena and its implications for the psychodynamic model of the mind, Neuropsychoanalysis, Vol: 9, Pages: 183-211, ISSN: 1529-4145
This paper reviews scientific literature on four subjective states: the dream state, the dreamy state of temporal lobe epilepsy and tem-poral lobe stimulation, the acute psychotic state, and the psychedelic state. Evidence is cited showing that underlying the emergence of dreamlike phenomena in all four states is the occurrence of high-voltage bursts of theta and slow-wave activity (2-8 Hz) in the me-dial temporal lobes. The medial temporal regions are recognized to play an important role in memory and emotion. In the dream state, medial temporal lobe bursts are tightly correlated with PGO waves. It has been widely speculated that PGO waves are direct neuro-physiological correlates of dreaming. On a phenomenological level, the dream state, the dreamy state, the acute psychotic state, and the psychedelic state have all been viewed as conducive to the emergence of unconscious material into consciousness. An argument is made that bursts of electrical activity spreading from the medial temporal lobes to the association cortices are the primary func-tional correlate of discharging psychical energies, experienced on a subjective level as the emergence of unconscious material into consciousness. The implications of these findings for the scientific legitimacy of the psychodynamic model are discussed. © 2007, Taylor & Francis Group, LLC. All rights reserved.
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