LSD alters dynamic integration and segregation in the human brain

Luppi, Andrea I.; Carhart‐Harris, Robin; Roseman, Leor; Pappas, Ioannis; Menon, David K.; Stamatakis, Emmanuel A.

doi:10.1016/j.neuroimage.2020.117653

Cited by 130 publications

(160 citation statements)

References 102 publications

(190 reference statements)

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…Since diffusion MRI was not acquired as part of the LSD study, the structural connectome used for network control theory analysis was identical to the one used in prior work 5 . Namely, we relied on diffusion data from the Human Connectome Project (HCP, http://www.humanconnectome.org/ ), specifically from 1021 subjects in the 1200-subject release 66 .…”

Section: Methodsmentioning

confidence: 99%

“…This is relevant because the changes in brain function under investigation in the present study arise from the administration of LSD. The serotonin 2a (5-HT2a) receptor is well established as the site responsible for the subjective [13][14][15][16][17] and neural [5][6][7] effects of LSD and other classic serotonergic psychedelics, and this receptor is not uniformly distributed across the brain 46 . Therefore, we sought to determine if the specific regional distribution of 5HT2a receptors in the brain could correspond to especially suitable control points for inducing a reduction in transition energy.…”

Section: Network Control Theory Reveals Lsd-induced Flattening Of the Brain's Energy Landscapementioning

confidence: 99%

“…We compared the overall mean of the energy matrix for each individual's 2a-weighted calculations versus all others and found that 5-HT2a was the most effective at lowering the overall energy to transition between empirically defined brain-states (Figure 4b). This is especially noteworthy because serotonin 2a receptor agonism plays a prominent role in how LSD and other classic psychedelics influence neural activity [5][6][7] and subjective experience [13][14][15][16][17] . Together, these results demonstrate that the 5-HT2a receptor is neurobiologically and spatially well-suited for energy landscape flattening -a key tenet of psychedelic action according to the REBUS model.…”

Section: Network Control Theory Reveals Lsd-induced Flattening Of the Brain's Energy Landscapementioning

confidence: 99%

“…It is well-known that even at rest the brain is not static, but rather it dynamically alternates between a number of recurrent states [9][10][11][12][13][14][15][16] . Such recurrent brain-states may be relevant for cognition [17][18][19][20] and even consciousness [21][22][23][24][25][26][27] , and have been shown to undergo prominent reorganization during the psychedelic state induced by LSD 5,6 and psilocybin 7,28 . Crucially, network control theory approaches enable mapping of the brain's energy landscape by quantifying the energy required to transition between these recurrent states (Figure 1a,b).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

Singleton

Luppi

Carhart-Harris

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Psychedelics like lysergic acid diethylamide (LSD) offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. The RElaxed Beliefs Under Psychedelics (REBUS) model postulates that 5-HT2a receptor agonism allows the brain to explore its dynamic landscape more readily, as suggested by more diverse (entropic) brain activity. Formally, this effect is theorized to correspond to a reduction in the energy required to transition between different brain-states, i.e. a ″flattening of the energy landscape.″ However, this hypothesis remains thus far untested. Here, we leverage network control theory to map the brain′s energy landscape, by quantifying the energy required to transition between recurrent brain states. In accordance with the REBUS model, we show that LSD reduces the energy required for brain-state transitions, and, furthermore, that this reduction in 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, we demonstrate the specific role of this receptor in flattening the brain′s energy landscape. Also, in accordance with REBUS, we show that the occupancy of bottom-up states is increased by LSD. In addition to validating fundamental predictions of the REBUS model of psychedelic action, this work highlights the potential of receptor-informed network control theory to provide mechanistic insights into pharmacological modulation of brain dynamics.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Network Control Theory Reveals Lsd-induced Flattening Of the Brain's Energy Landscapementioning

confidence: 99%

Section: Network Control Theory Reveals Lsd-induced Flattening Of the Brain's Energy Landscapementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

Singleton

Luppi

Carhart-Harris

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, it has been shown that brain dynamics are significantly altered when consciousness is suppressed by anaesthesia or severe brain injury (Luppi et.al. 2019;Luppi et al, 2020;Huang et al, 2020;Demertzi et al, 2019;Barttfeld et al, 2015), or altered by psychedelics (Atasoy et al, 2017, Lord et al 2019, Luppi et al, 2020c, Luppi et al, 2020d. These results highlight the key role of neural dynamics for consciousness, vindicating the approach adopted by Tononi, Sporns, and Edelman (1998).…”

Section: Decomposing Information Flowmentioning

confidence: 89%

What it is like to be a bit: An Integrated Information Decomposition account of emergent mental phenomena

Luppi¹,

Mediano²,

Rosas³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

A central question in neuroscience concerns the relationship between consciousness and its physical substrate. Here, we argue that a richer characterisation of consciousness can be obtained by viewing it not as a monolithic construct, but rather as constituted of distinct information-theoretic elements. In other words, we propose a shift from quantification of consciousness - viewed as integrated information - to its decomposition. Through this approach, termed Integrated Information Decomposition (ΦID), we lay out a formal argument that whether the consciousness of a given system is an emergent phenomenon depends on its information-theoretic composition - thus providing a principled answer to the long-standing dispute on the relationship between consciousness and emergence. Furthermore, we show that two organisms may attain the same amount of integrated information, yet differ in its information-theoretic composition. Building on ΦID’s revised understanding of integrated information, termed ΦR, we also introduce the notion of ΦR-ing rate to quantify how efficiently an entity uses information for conscious processing. A combination of ΦR and ΦR-ing rate may provide an important way to compare the neural basis of different aspects of consciousness. Thus, decomposition of consciousness enables us to identify qualitatively different ‘modes of consciousness,’ which establish a common space for mapping the phenomenology of different conscious states. We outline both theoretical and empirical avenues to carry out such mapping between phenomenology and information-theoretic modes, starting from a central feature of everyday consciousness: selfhood. Overall, Integrated Information Decomposition yields rich new ways to explore the relationship between information, consciousness, and its emergence from neural dynamics.

show abstract

Brain network integration dynamics are associated with loss and recovery of consciousness induced by sevoflurane

Luppi

Golkowski

Ranft

et al. 2021

Human Brain Mapping

Self Cite

View full text Add to dashboard Cite

The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a sub‐state where integration predominates, and a predominantly segregated sub‐state, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare resting‐state functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished small‐world character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burst‐suppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain's default mode and executive control networks dynamically reconfigure depending on the brain's state of integration or segregation. Taken together, our results demonstrate that the integrated sub‐state of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery.

show abstract

LSD alters dynamic integration and segregation in the human brain

Cited by 130 publications

References 102 publications

LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

What it is like to be a bit: An Integrated Information Decomposition account of emergent mental phenomena

Brain network integration dynamics are associated with loss and recovery of consciousness induced by sevoflurane

Contact Info

Product

Resources

About