Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD

Deco, Gustavo; Cruzat, Josephine; Cabral, Joana; Knudsen, Gitte M.; Carhart‐Harris, Robin; Whybrow, Peter C.; Logothetis, Nikos K.; Kringelbach, Morten L.

doi:10.1016/j.cub.2018.07.083

Cited by 188 publications

(347 citation statements)

References 99 publications

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“…3), which suggests that their entropy increase in experimental data might be directly related to the high 5HT2A-R density in those regions. Together, these findings support the conclusion that the DMF model, once optimised, can reproduce not only functional connectivity, 18 but also some of the most salient localised entropy increases found on in vivo human studies up to date.…”

Section: Comparison To In Vivo Experiments With Psychedelic Drugssupporting

confidence: 79%

“…We simulated whole-brain activity using the Dynamic Mean-Field (DMF) model by Deco et al, 19 using parameter values fit to reproduce the dynamics of fMRI recordings in humans during wakeful rest, as well as under the acute effects of LSD. 18 The model consists of interacting pools of excitatory and inhibitory neural populations, coupled via long-range excitatory connections informed by the anatomical connectivity of the brain. The DMF model combines a theoretical model of neural and synaptic dynamics with two empirical sources of information about the human brain: the human connectome, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…[15][16][17] A recent simulation study involving whole-brain computational modelling confirmed that the topographic distribution of 5HT2A-R in the human brain is critical to reproduce the functional connectivity dynamics of human fMRI data recorded under the acute effects of LSD. 18 Here we build upon this model to characterise the interplay between the entropy of brain signals, the distribution of 5HT2A receptors, and structural connectivity properties of the brain, with the overarching goal of explaining the sources of entropic effects, and thus altered consciousness, elicited by psychedelic drugs.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Comparison To In Vivo Experiments With Psychedelic Drugssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Herzog

Mediano

Rosas

et al. 2020

Preprint

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“…Traditionally, whole-brain models have been relatively successful in linking structural connectivity with functional dynamics (Breakspear, 2017;Deco and Kringelbach, 2014). This has revealed important new mechanistic principles of brain function (Deco et al, 2018;Deco et al, 2019a;Deco et al, 2019b;Deco et al, 2017e;Honey et al, 2007). Nevertheless, the present causal characterisation of whole-brain information flow offers a new avenue for generating even more useful models.…”

Section: Causal Confirmation Using Novel Generative Whole-brain Modelmentioning

confidence: 99%

Revisiting the Global Workspace: Orchestration of the functional hierarchical organisation of the human brain

Deco

Vidaurre

Kringelbach

2019

Preprint

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A central, unsolved challenge in neuroscience is how the brain orchestrates function by organising the flow of information necessary for the underlying computation. It has been argued that this whole-brain orchestration is carried out by a core subset of integrative brain regions, commonly referred to as the 'global workspace', although quantifying the constitutive brain regions has proven elusive. We developed a normalised directed transfer entropy (NDTE) framework for determining the pairwise bidirectional causal flow between brain regions and applied it to multimodal wholebrain neuroimaging from over 1000 healthy participants. We established the full brain hierarchy and common regions in a 'functional rich club' (FRIC) coordinating the functional hierarchical organisation during rest and task. FRIC contains the core set of regions, which similar to a 'club' of functional hubs are characterized by a tendency to be more densely functionally connected among themselves than to the rest of brain regions from where they integrate information. The invariant global workspace is the intersection of FRICs across rest and seven tasks, and was found to consist of the precuneus, posterior and isthmus cingulate cortices, nucleus accumbens, putamen, hippocampus and amygdala that orchestrate the functional hierarchical organisation based on information from perceptual, long-term memory, evaluative and attentional systems. We confirmed the causal significance and robustness of this invariant global workspace by systematically lesioning a generative whole-brain model accurately simulating the functional hierarchy defined by NDTE. Overall, this is a major step forward in understanding the complex choreography of information flow within the functional hierarchical organisation of the human brain.

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“…Both are serotonin (5HT2AR) agonists, while ketamine -which at low (sub-anesthetic) doses also has psychedelic-like properties -is primarily an NMDA antagonist (Sleigh et al, 2014). Many studies now link the subjective effects of psychedelics to altered activity at these receptors (Preller et al, 2018;Deco et al, 2018). However, despite these links, the large-scale changes in neural dynamics that underlie the dramatic subjective effects of psychedelics remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Decreased Directed Functional Connectivity in the Psychedelic State

Barnett

Muthukumaraswamy

Carhart‐Harris

et al. 2019

Preprint

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Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the largescale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

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Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD

Cited by 188 publications

References 99 publications

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

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

Revisiting the Global Workspace: Orchestration of the functional hierarchical organisation of the human brain

Decreased Directed Functional Connectivity in the Psychedelic State

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