Psychedelics as a treatment for disorders of consciousness

Scott, Gregory; Carhart‐Harris, Robin

doi:10.1093/nc/niz003

Cited by 46 publications

(81 citation statements)

References 65 publications

(100 reference statements)

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“…6D). Prior studies have reported global hyperconnectivity of fMRI signals in schizophrenic patients (34), as well as shared phenomenology between schizophrenic symptoms and ketamine's dissociative/ psychoactive effects (30,32). All participants receiving ketamine reported having dreams, and 8 of 12 participants in our study could recall their hallucinations (e.g., flying on a cloud, weird smells, taking an elevator, and thick mist) after recovery from anesthesia.…”

Section: Distinct Spatiotemporal Characteristics During Behavioral Unmentioning

confidence: 64%

“…We assessed whether the suppression of DMN+ and DAT+ is specific to the reduced level of responsiveness as opposed to disorders of cognitive function in general. Another motivation was to further understand the ketamine-specific alterations in the CAP occurrence rates, as altered states of consciousness induced by ketamine are often associated with psychoactive effects and unique brain dynamics (30)(31)(32). Using the same method applied in the task dataset (i.e., maximal similarity to the predefined CAP centroids from the main cohort), we identified eight comparable CAPs in the psychiatric cohort ( Fig.…”

Section: Stimulus Modulations Of Caps and Control Analysis In Psychiamentioning

confidence: 99%

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Temporal circuit of macroscale dynamic brain activity supports human consciousness

et al. 2020

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The ongoing stream of human consciousness relies on two distinct cortical systems, the default mode network and the dorsal attention network, which alternate their activity in an anticorrelated manner. We examined how the two systems are regulated in the conscious brain and how they are disrupted when consciousness is diminished. We provide evidence for a “temporal circuit” characterized by a set of trajectories along which dynamic brain activity occurs. We demonstrate that the transitions between default mode and dorsal attention networks are embedded in this temporal circuit, in which a balanced reciprocal accessibility of brain states is characteristic of consciousness. Conversely, isolation of the default mode and dorsal attention networks from the temporal circuit is associated with unresponsiveness of diverse etiologies. These findings advance the foundational understanding of the functional role of anticorrelated systems in consciousness.

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Section: Distinct Spatiotemporal Characteristics During Behavioral Unmentioning

confidence: 64%

Section: Stimulus Modulations Of Caps and Control Analysis In Psychiamentioning

confidence: 99%

Temporal circuit of macroscale dynamic brain activity supports human consciousness

et al. 2020

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“…Such a framework could potentially make individualised predictions of the action of serotonergic psychedelics on specific individuals, aiding patient stratification and treatment customization. 2 Finally, it is worth noting that all our analyses here are based on the univariate statistics of individual brain regions, not including any correlation or information flow between them. However, it is known that some high-level subjective effects of psychedelics (such as complex imagery 7 and ego dissolution 28 ) are related to network, as opposed to single region, dynamics.…”

Section: Current Limitations and Future Researchmentioning

confidence: 99%

“…Psychedelic drugs provide a privileged opportunity to study the mind-brain relationship, and promise to revolutionise some of our current mental health treatments. [1][2][3] However, while some aspects of the neurochemical action of psychedelics at the neuronal and sub-neuronal level are well known, 4,5 our current understanding of their action at the whole-brain level, is still very limited. A deeper understanding of the mechanisms that trigger the changes in conscious experience produced by psychedelics would greatly advance our knowledge of human consciousness, and medical development of psychedelics.…”

Section: Introductionmentioning

confidence: 99%

A mechanistic model of the neural entropy increase elicited by psychedelic drugs

Herzog

Mediano

Rosas

et al. 2020

Preprint

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Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this 'entropic' phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

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“…Interestingly, the positive therapeutic effects seem to scale with "peak" or mystical experience in the psychedelic state (Roseman, Nutt, & Carhart-Harris, 2018). Psychedelics have been shown to be effective in treating depression (Lyons & Carhart-Harris, 2018;Palhano-Fontes et al, 2019), obsessivecompulsive disorder (Moreno, Wiegand, Taitano, & Delgado, 2006), end of life existential distress (Griffiths et al, 2016), and have even been proposed as a potential treatment for disorders of consciousness such as the vegetative state and the minimally conscious state (Scott & Carhart-Harris, 2019). Carhart-Harris interprets the therapeutic effects as a result of "relaxing" high-level beliefs, allowing for a revision of pathological beliefs that have become overly dominant and resistant to revision, coined the "TIghtened BEliefs in Response to uncertainty" (TIBER) model (Carhart-Harris, 2019).…”

Section: Psychedelic Therapymentioning

confidence: 99%

Dissolving the self

Deane

2020

PhiMiSci

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Psychedelic drugs such as psilocybin, LSD and DMT are known to induce powerful alterations in phenomenology. Perhaps of most philosophical and scientific interest is their capacity to disrupt and even “dissolve” one of the most primary features of normal experience: that of being a self. Such “peak” or “mystical” experiences are of increasing interest for their potentially transformative therapeutic value. While empirical research is underway, a theoretical conception of the mechanisms underpinning these experiences remains elusive. In the following paper, psychedelic-induced ego-dissolution is accounted for within an active inference framework, as a collapse in the “temporal thickness” of an agent’s deep temporal model, as a result of lowered precision on high-level priors. The argument here is composed of three moves: first, a view of the self-model is proposed as arising within a temporally deep generative model of an embodied organism navigating an affordance landscape in the service of allostasis. Next, a view of the action of psychedelics as lowering the precision of high-level priors within the generative model is unpacked in terms of a high Bayesian learning rate. Finally, the relaxation of high-level priors is argued to cause a “collapse” in the temporal thickness of the generative model, resulting in a collapse in the self-model and a loss of the ordinary sense of being a self. This account has implications for our understanding of ordinary self-consciousness and disruptions in self-consciousness present in psychosis, autism, depression, and dissociative disorders. The philosophical, theoretical and therapeutic implications of this account are touched upon.

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Psychedelics as a treatment for disorders of consciousness

Cited by 46 publications

References 65 publications

Temporal circuit of macroscale dynamic brain activity supports human consciousness

Temporal circuit of macroscale dynamic brain activity supports human consciousness

A mechanistic model of the neural entropy increase elicited by psychedelic drugs

Dissolving the self

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