Imperial College London

DrLeorRoseman

Faculty of MedicineDepartment of Brain Sciences

Research Associate
 
 
 
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leor.roseman13

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

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56 results found

Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris Ret al., 2022, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression., J Psychopharmacol

BACKGROUND: Music listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion. AIMS: The present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired. METHODS: Nineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked 'pleasure' plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith-Hamilton Pleasure Scale). RESULTS: Results revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music). CONCLUSION: These results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.

Journal article

Spriggs MJ, Giribaldi B, Lyons T, Rosas FE, Kaertner LS, Buchborn T, Douglass HM, Roseman L, Timmermann C, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2022, Body mass index (BMI) does not predict responses to psilocybin, JOURNAL OF PSYCHOPHARMACOLOGY, ISSN: 0269-8811

Journal article

Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, Timmermann C, Nour MM, Kaelen M, Nutt D, Carhart-Harris R, Roseman Let al., 2022, The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 3461-3483, ISSN: 0033-3158

Journal article

Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Spreng RNet al., 2022, Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex, NEUROIMAGE, Vol: 256, ISSN: 1053-8119

Journal article

Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Golkowski D, Ranft A, Ilg R, Jordan D, Peattie ARD, Manktelow AE, de Araujo DB, Sensi SL, Owen AM, Naci L, Menon DK, Misic B, Stamatakis EAet al., 2022, Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape

<jats:title>Abstract</jats:title><jats:p>To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 18 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 7 different mind-altering drugs including anaesthetics, psychedelics, and cognitive enhancers. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. Intriguingly, the effects of both anaesthetics and psychedelics on brain function, though opposite, are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.</jats:p>

Journal article

Daws R, Timmermann C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris Ret al., 2022, Increased global integration in the brain after psilocybin therapy for depression, Nature Medicine, Vol: 28, ISSN: 1078-8956

Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the sub-acute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7 days apart) in treatment-resistant depression (TRD). fMRI was recorded at baseline and one day after the 25mg dose. Beck’s depression inventory (BDI) was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase 2 randomised control trial (DB-RCT) comparing psilocybin therapy with escitalopram. Major depressive disorder (MDD) patients received either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’); or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI wasrecorded at baseline and 3 weeks after the 2nd psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in functional MRI (fMRI) brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brainnetwork integration. Network cartography analyses indicated that 5-HT2A receptor rich higher-order functional networks became more functionally inter-connected and flexible post psilocybin. The antidepressant response to escitalopram was milder and no changes in brain network organisation were observed. Consistent efficacy related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: Global increases in brain network integration.

Journal article

Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RLet al., 2022, Increased low-frequency brain responses to music after psilocybin therapy for depression

<jats:title>Abstract</jats:title><jats:p>Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.</jats:p>

Journal article

Hadar A, David J, Shalit N, Roseman L, Gross R, Sessa B, Lev-Ran Set al., 2022, The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Classical Psychedelics, JOURNAL OF PSYCHOACTIVE DRUGS, ISSN: 0279-1072

Journal article

Peill JM, Trinci KE, Kettner H, Mertens LJ, Roseman L, Timmermann C, Rosas FE, Lyons T, Carhart-Harris RLet al., 2022, Validation of the psychological insight scale: a new scale to assess psychological insight following a psychedelic experience, Journal of Psychopharmacology, Vol: 36, Pages: 31-45, ISSN: 0269-8811

Introduction:As their name suggests, ‘psychedelic’ (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS).Methods:The PIS is a six- to seven-item questionnaire that enquires about psychological insight after a psychedelic experience (PIS-6) and accompanied behavioural changes (PIS item 7). In total, 886 participants took part in a study in which the PIS and other questionnaires were completed in a prospective fashion in relation to a planned psychedelic experience. For validation purposes, data from 279 participants were analysed from a non-specific ‘global psychedelic survey’ study.Results:Principal components analysis of PIS scores revealed a principal component explaining 73.57% of the variance, which displayed high internal consistency at multiple timepoints throughout the study (average Cronbach’s α = 0.94). Criterion validity was confirmed using the global psychedelic survey study, and convergent validity was confirmed via the Therapeutic-Realizations Scale. Furthermore, PIS scores significantly mediated the relationship between emotional breakthrough and long-term well-being.Conclusion:The PIS is complementary to current subjective measures used in psychedelic studies, most of which are completed in relation to the acute experience. Insight – as measured by the PIS – was found to be a key mediator of long-term psychological outcomes following a psychedelic experience. Future research may investigate how insight varies throughout a psychedelic process, its underlying neurobiology and how it impacts behaviour and mental health.

Journal article

Timmermann Slater CB, Kettner H, Letheby C, Roseman L, Rosas F, Carhart-Harris Ret al., 2021, Psychedelics alter metaphysical beliefs, Scientific Reports, Vol: 11, Pages: 1-12, ISSN: 2045-2322

Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post-psychedelic-use were consolidated by data from an independent controlled clinical trial. Together, these findings imply that psychedelic-use may causally influence metaphysical beliefs—shifting them away from ‘hard materialism’. We discuss whether these apparent effects are contextually independent.

Journal article

Bornemann J, Close JB, Spriggs MJ, Carhart-Harris R, Roseman Let al., 2021, Self-medication for chronic pain using classic psychedelics: a qualitative investigation to inform future research, Frontiers in Psychiatry, section Psychological Therapies, Vol: 12, Pages: 1-17, ISSN: 1664-0640

Background: Chronic Pain is among the leading causes of disability worldwide with up to60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recentlybeen found effective in treating a host of mental health issues including depression and hashistorically been found to be useful in treating pain. Reports of self-medication for chronic painusing psychedelic drugs have been widely documented, with anecdotal evidence indicatingwidespread success in a range of pathologies. Aims: In preparation for an upcoming trial, tobetter understand how those with lived experience of chronic pain self-medicate withpsychedelic drugs, and to establish, in detail, their therapeutic protocols and practices forsuccess. Methods: As part of patient-involvement (PI) for an upcoming trial in this population,11 individuals who reported self-medicating with psychedelic drugs took part in a one-hoursemi-structured discussion, which was then transcribed and thematically analysed. Results:Across a range of psychedelic substances and doses, reported pain scores improvedsubstantially during and after psychedelic experiences. Two processes, Positive Reframing andSomatic Presence, were reliably identified as playing a role in improvements in mentalwellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies suchas mindfulness, breathwork, and movement were also widely reported. Due to the data’ssubjective nature, this paper is vulnerable to bias and makes no claims on causality orgeneralisability. Together, these results have been used to inform study design for aforthcoming trial. Conclusion: This pre-trial PI work gives us confidence to test psychedelictherapy for chronic pain in a forthcoming controlled trial. The results presented here will beinstrumental in improving our ability to meet the needs of future study participants.

Journal article

Roseman L, Karkabi N, 2021, On revelations and revolutions: drinking ayahuasca among Palestinians under Israeli occupation, Frontiers in Psychology, Vol: 12, Pages: 1-14, ISSN: 1664-1078

The ritualistic use of ayahuasca can induce a feeling of unity and harmony among group members. However, such depoliticized feelings can come in the service of a destructive political status quo in which Palestinians are marginalized. Through 31 in-depth interviews of Israelis and Palestinians who drink ayahuasca together, and through participatory observations, such rituals were examined. In this setting marginalization was structurally rooted by the group’s inability to recognize Palestiniannational identity or admit the ongoing Israeli injustice toward Palestinians. Although the groups avoided politics, they still find their way into these rituals. This happened through occasional ayahuasca-induced revelatory events, in which individuals were confronted with a pressing truth related to the oppressive relations between Jewish Israelis and Palestinians. Three case studies of such revelatory events are described in this paper. Affected by emotions of pain, anger, and guilt, these participants developed resistance toward the hegemonic Israeli ritual structure. This was followed by an urge to deliver an emancipatory message to the rest of the group, usually through a song. Moreover, affected subjects developed a long-lasting fidelity to the truth attained at these events. In time, this fidelity led to the expansion of ayahuasca practices to other Palestinians and the17 politicization of the practice. The article draws on Badiou’s theory in Being and Event (1988) to analyze18 the relations between the Israeli ritual structure, the Palestinian revelatory event, and the19 emancipatory fidelity that followed. Badiou’s theory elucidates the egalitarian revolutionary potential,20 which is part of the sociopsychopharmacology of psychedelics.

Journal article

Timmermann C, Kettner H, Letheby C, Roseman L, Rosas F, Carhart-Harris Ret al., 2021, Psychedelics alter metaphysical beliefs

<p>Are psychedelics able to induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this has never been systematically tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. These changes remained detectable at 6 months, and were associated with the extent of past use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post psychedelic use were confirmed by data from an independent controlled clinical trial. Together, these findings imply that psychedelic use has a causal influence on metaphysical beliefs – shifting them away from ‘hard materialism’.</p>

Journal article

Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski Aet al., 2021, LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

<jats:title>Abstract</jats:title><jats:p>Psychedelics like lysergic acid diethylamide (LSD) and psilocybin offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. A recent model postulates that serotonin 2a (5-HT2a) receptor agonism allows the brain to explore its dynamic landscape more readily, as reflected by more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain’s control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states measured using functional magnetic resonance imaging (fMRI) in individuals under LSD, psilocybin, and placebo conditions. We show that LSD and psilocybin reduce the amount of control energy required for brain state transitions, and, furthermore, that, across individuals, LSD’s reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors from publicly available (non-drug) positron emission tomography (PET) maps, we demonstrate the specific role of this receptor in reducing control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, by combining receptor-informed network control theory with pharmacological modulation, our work highlights the potential of this approach in studying the impacts of targeted neuropharmacological manipulation on brain activity dynamics.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>We present a multi-modal framework for quantifying the effects of two psychedelic drugs (LSD and psilocybin) on br

Journal article

Roseman L, Ron Y, Saca A, Ginsberg N, Luan L, Karkabi N, Doblin R, Carhart-Harris Ret al., 2021, Relational processes in Ayahuasca groups of Palestinians and Israelis, Frontiers in Pharmacology, Vol: 12, Pages: 1-18, ISSN: 1663-9812

Psychedelics are used in many group contexts. However, most phenomenological research on psychedelics is focused on personal experiences. This paper presents a phenomenological investigation centred on intersubjective and intercultural relational processes, exploring how an intercultural context affects both the group and individual process. Through 31 in-depth interviews, ceremonies in which Palestinians and Israelis drink ayahuasca together have been investigated. The overarching question guiding this inquiry was how psychedelics might contribute to processes of peacebuilding, and in particular how an intercultural context, embedded in a protracted conflict, would affect the group’s psychedelic process in a relational sense. Analysis of the interviews was based on grounded theory. Three relational themes about multiocal participatory events which occurred during ayahuasca rituals have emerged from the interviews: (1) Unity-Based Connection – collective events in which a feeling of unity and ‘oneness’ is experienced, whereby participants related to each other based upon a sense of shared humanity, and other social identities seemed to dissolve (such as national and religious identities). (2) Recognition and Difference-Based Connection – events where a strong connection was made to the other culture. These events occurred through the expression of the other culture or religion through music or prayers, which resulted in feelings of awe and reverence (3) Conflict-related revelations – events where participants revisited personal or historical traumatic elements related to the conflict, usually through visions. These events were triggered by the presence of ‘the Other’, and there was a political undertone in those personal visions. This inquiry has revealed that psychedelic ceremonies have the potential to contribute to peacebuilding. This can happen not just by ‘dissolution of identities’, but also by provid

Journal article

Kettner HS, Rosas F, Timmermann C, Kärtner L, Carhart-Harris RL, Roseman Let al., 2021, Psychedelic Communitas: intersubjective experience during psychedelic group sessions predicts enduring changes in psychological wellbeing and social connectedness, Frontiers in Pharmacology, Vol: 12, ISSN: 1663-9812

Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adapted Communitas Scale, assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats.Methods: In this observational, web-based survey study, participants (N = 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored.Results: The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r = 0.22), social connectedness (r = 0.25), and other salient mental health outcomes. Path

Journal article

Luppi A, Carhart-Harris RL, Roseman L, Pappas I, Menon DK, Stamatakis EAet al., 2021, LSD alters dynamic integration and segregation in the human brain, NEUROIMAGE, Vol: 227, ISSN: 1053-8119

Journal article

Jobst BM, Atasoy S, Ponce-Alvarez A, Sanjuan A, Roseman L, Kaelen M, Carhart-Harris R, Kringelbach ML, Deco Get al., 2021, Increased sensitivity to strong perturbations in a whole-brain model of LSD, NEUROIMAGE, Vol: 230, ISSN: 1053-8119

Journal article

Kaertner L, Steinborn M, Kettner H, Spriggs M, Roseman L, Buchborn T, Timmermann Slater C, Erritzoe D, Carhart-Harris Ret al., 2021, Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing, Scientific Reports, Vol: 11, ISSN: 2045-2322

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classicpsychedelic substances. Anecdotal reports and observational studies suggest that microdosingmay promote positive mood and well-being, but recent placebo-controlled studies failed to fndcompelling evidence for this. The present study collected web-based mental health and related datausing a prospective (before, during and after) design. Individuals planning a weekly microdosingregimen completed surveys at strategic timepoints, spanning a core four-week test period. Eightyone participants completed the primary study endpoint. Results revealed increased self-reportedpsychological well-being, emotional stability and reductions in state anxiety and depressivesymptoms at the four-week primary endpoint, plus increases in psychological resilience, socialconnectedness, agreeableness, nature relatedness and aspects of psychological fexibility. However,positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestiveof a signifcant placebo response. This study highlights a role for positive expectancy in predictingpositive outcomes following psychedelic microdosing and cautions against zealous inferences on itsputative therapeutic value.

Journal article

Jobst BM, Atasoy S, Ponce-Alvarez A, Sanjuán A, Roseman L, Kaelen M, Carhat-Harris R, Kringelbach ML, Deco Get al., 2021, Increased sensitivity to strong perturbations in a whole-brain model of LSD

<jats:title>Abstract</jats:title><jats:p>Lysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain’s global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into th

Journal article

Mediano PAM, Rosas FE, Timmermann C, Roseman L, Nutt DJ, Feilding A, Kaelen M, Kringelbach ML, Barrett AB, Seth AK, Muthukumaraswamy S, Bor D, Carhart-Harris RLet al., 2020, Effects of external stimulation on psychedelic state neurodynamics

<jats:p>Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g. from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience, by studying participants under the effects of LSD or placebo, either with gross state changes (eyes closed vs. open) or different stimulus (no stimulus vs. music vs. video). Results show that while brain entropy increases with LSD in all the experimental conditions, it exhibits largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing video — potentially due to a “competition” between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence for the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment. Additionally, our findings put into question simplistic interpretations of brain entropy as a direct neural correlate of conscious level.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>The effects of psychedelic substances on conscious experience can be substantially affected by contextual factors, which play a critical role

Journal article

Varley TF, Carhart-Harris R, Roseman L, Menon DK, Stamatakis EAet al., 2020, Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains, NEUROIMAGE, Vol: 220, ISSN: 1053-8119

Journal article

Luppi AI, Vohryzek J, Kringelbach ML, Mediano PAM, Craig MM, Adapa R, Carhart-Harris RL, Roseman L, Pappas I, Peattie ARD, Manktelow AE, Sahakian BJ, Finoia P, Williams GB, Allanson J, Pickard JD, Menon DK, Atasoy S, Stamatakis EAet al., 2020, Distributed harmonic patterns of structure-function dependence orchestrate human consciousness

<jats:title><jats:bold>Abstract</jats:bold></jats:title><jats:p>A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Departing from the predominant location- centric view in neuroimaging, here we provide an alternative perspective on the neural signatures of human consciousness: one that is intrinsically centered on how the distributed network architecture of the human structural connectome shapes functional activation across scales. We decompose cortical dynamics of resting-state functional MRI into fundamental distributed patterns of structure- function association: the harmonic modes of the human structural connectome. We contrast wakefulness with a wide spectrum of states of consciousness, spanning chronic disorders of consciousness but also pharmacological perturbations of consciousness induced with the anaesthetic propofol and the psychoactive drugs ketamine and LSD. Decomposing this wide spectrum of states of consciousness in terms of “connectome harmonics” reveals a generalisable structure-function signature of loss of consciousness, whether due to anaesthesia or brain injury. A mirror-reverse of this harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure. The topology and neuroanatomy of the human connectome are crucial for shaping the repertoire of connectome harmonics into a fine-tuned indicator of consciousness, correlating with physiological and subjective scores across datasets and capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. Overall, connectome harmonic decomposition identifies meaningful relationships between neurobiology, brain function, and conscious experience.</jats:p>

Journal article

Girn M, Mills C, Roseman L, Carhart-Harris RL, Christoff Ket al., 2020, Updating the dynamic framework of thought: Creativity and psychedelics, NEUROIMAGE, Vol: 213, ISSN: 1053-8119

Journal article

Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Spreng RNet al., 2020, Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

<jats:title>Abstract</jats:title><jats:p>LSD and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to pharmacological resting-state fMRI data to assess cortical organization in the LSD and psilocybin state. Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes – default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping confirmed that this was underpinned by increased unimodal-transmodal crosstalk. In addition, LSD-dependent principal gradient changes tracked changes in self-reported ego-dissolution. Results involving the second and third gradient, which respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to a pharmacological manipulation, specifically highlighting an important relationship between cortical organization

Journal article

Close JB, Hajien EC, Watts R, Roseman L, Carhart-Harris RLet al., 2020, Psychedelics and psychological flexibility - Results of a prospective web-survey using the Acceptance and Action Questionnaire II, JOURNAL OF CONTEXTUAL BEHAVIORAL SCIENCE, Vol: 16, Pages: 37-44, ISSN: 2212-1447

Journal article

Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RLet al., 2020, Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 167-180, ISSN: 0269-8811

Journal article

Timmermann Slater CB, Roseman L, Schartner M, Milliere R, Williams L, Erritzoe D, Muthukumaraswamy S, Ashton M, Bendrioua A, Kaur O, Turton S, Nour M, Day C, Leech R, Nutt D, Carhart-Harris Ret al., 2019, Neural correlates of the DMT experience as assessed with multivariate EEG, Scientific Reports, Vol: 9, Pages: 1-13, ISSN: 2045-2322

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 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.

Journal article

Roseman L, 2019, Functional imaging investigation of psychedelic visual imagery

Psychedelics can induce eyes-closed imagery in which various visions can be experienced. These visions vary from simple geometrical patterns, to more complex imagery, to full immersion within “other realms”. Past studies suggest that the visual cortex is involved in processing these visions, yet these studies were limited into investigation of activity. In this thesis, the aim was to expand on the involvement of the visual cortex by investigating processes that are beyond simple activation maps, such as functional connectivity and dynamics. In study 1, it was hypothesized that the visual cortex will show increased functional connectivity with many cortical and subcortical regions. This was investigated with 15 subjects that were scanned using fMRI under the influence of 75 µg of LSD or placebo. The results of this study showed increased resting state functional connectivity (RSFC) between the primary visual cortex and many cortical and subcortical regions. This result correlated with subjective ratings of psychedelic imagery and with occipital alpha power suppression measured with MEG, which is a reliable neural correlate of the intensity of the psychedelic state. It study 2, it was hypothesized that connectivity within the visual cortex would match its retinotopic architecture. Retinotopic mapping is the representation of the visual field (the world we observe) in the visual cortex – e.g. areas which are near to each other in the visual field will be near each other in the visual cortex. In this study, it was found that under LSD (same procedure as study 1), with eyes closed, connectivity patterns between different subregions of the visual cortex matched the retinotopic mapping of these regions, suggesting that the visual system behaves as if it is seeing spatially localized input, with eyes-closed under LSD. In study 3, it was hypothesized that during the onset phase of psychedelic imagery, the activation of subregions of the visual cortex

Thesis dissertation

Lord L-D, Expert P, Atasoy S, Roseman L, Rapuano K, Lambiotte R, Nutt DJ, Deco G, Carhart-Harris RL, Kringelbach ML, Cabral Jet al., 2019, Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin, NeuroImage, Vol: 199, Pages: 127-142, ISSN: 1053-8119

Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns ('functional brain networks'), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in "magic mushrooms". We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.

Journal article

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