Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention

Barrett, Frederick S.; Krimmel, Samuel R.; Griffiths, Roland R.; Seminowicz, David A.; Mathur, Brian N.

doi:10.1016/j.neuroimage.2020.116980

Cited by 111 publications

(119 citation statements)

References 94 publications

(131 reference statements)

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“…Perturbing the activity in these specific regions (via 5HT2A-R agonism) could have particularly profound implications for the regularity of brain activity and the quality of conscious experience. However, sub cortical regions may also play an important role on the modulation of brain activity, conscious experience, and the psychedelic state 33 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: A mechanistic model of the neural entropy increase elicited by psychedelic drugs

Herzog

Mediano

Rosas

et al. 2020

Sci Rep

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Psychedelic drugs, including lysergic acid diethylamide 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, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase 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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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: A mechanistic model of the neural entropy increase elicited by psychedelic drugs

Herzog

Mediano

Rosas

et al. 2020

Sci Rep

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“…Future application of this novel approach using multiple datasets may shed light on which neural mechanisms, such as increased DMN entropy 40 , disruption of thalamocortical circuits 55 , or disruption of claustrocortical circuits 56 are common among or unique between different hallucinogens. Investigation of the claustrum, a structure thought to contribute to consciousness and delusional states, may especially be a fruitful avenue for future work considering the high expression of 5-HT 2A , NMDA, and κ-opioid receptors in the claustrum [57][58][59] and given recent developments in measuring claustrum function in humans using fMRI 60,61 . One of the most robust effects of salvinorin A was a decrease in sFC within the DMN, and using connectomebased classification, we found within-DMN sFC and eFC to be especially predictive of the effects of SA on brain function compared to other network interactions.…”

Section: Discussionmentioning

confidence: 99%

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Doss

May

Johnson

et al. 2020

Sci Rep

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Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.

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“…Moreover, while 5-HT 2A receptors are predominately found in cortex (Supplementary Fig. 1A-C), future work can incorporate the 5-HT 2A receptorrich claustrum ( Hall et al, 2000 ), which may play a role in mediating the effects of serotonergic psychedelics ( Barrett et al, 2020 ). Comparing pharmacological models to data from multiple imaging modalities may also generate new and complementary insights: for instance, the mechanisms underlying LSD-induced changes in broadband oscillatory power ( Muthukumaraswamy et al, 2013; Carhart-Harris et al, 2016 ) and increased neural signal diversity ( Schartner et al, 2017 ) remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD

Burt

Preller

Demirtaş

et al. 2021

Preprint

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Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically-induced effects. This paradigm has revealed that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to its agonist activity at the serotonin-2A receptor. Here, we integrate brainwide transcriptomics with biophysically-based large-scale circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical dynamics. Our model captures the topographic effects of LSD-induced changes in cortical BOLD functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal cell gain is the circuit mechanism through which LSD alters cortical functional topography. Individual-subject fitting reveals that the model captures patterns of individual neural differences in drug response that predict altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to salient changes in brain function, with implications for precision medicine.

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Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention

Cited by 111 publications

References 94 publications

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

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

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD

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