Neuroimage
May 25, 2019
Louis-David Lord, Paul Expert, Selen Atasoy et al.
249 citations
Brain function can be understood as the exploration of a repertoire of metastable connectivity patterns that underlie different mental processes. Intravenous infusion of psilocybin rapidly modulates how the brain dynamically explores these resting-state networks. Using a data-driven approach focused on the leading eigenvector of BOLD phase coherence at single-TR resolution, recurrent BOLD phase-locking patterns were assessed pre- and post-infusion. A frontoparietal subsystem pattern was strongly destabilized after psilocybin, while a pattern characterized by global BOLD phase coherence became more probable. These results demonstrate network-specific neuromodulation by psilocybin, bridging molecular pharmacodynamics and whole-brain network dynamics.
Neuroscience & Biobehavioral Reviews
May 5, 2015
Federico Turkheimer, Robert Leech, Paul Expert et al.
64 citations
The brain appears to use repeated computational building blocks—canonical computational motifs—that are similar across species, brain areas, and sensory modalities. These motifs, grounded in stereotyped neuronal circuits and inhibitory interneurons, operate at micro-, meso-, and macro-scales to form a multiplexing information system capable of encoding and transmitting increasingly complex information. Similar activation patterns are observed in primary sensory cortices via electrophysiology and in large-scale networks measured with fMRI. The authors apply this canonical model to unify evidence on the pathophysiology of schizophrenia and suggest it may extend to other brain disorders involving GABA interneuron dysfunction.
Brain communications
January 1, 2024
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
33 citations
Psilocybin therapy for depression shows promise, but its causal mechanisms are unknown. By comparing brain dynamics in treatment responders (those with >50% symptom reduction) and non-responders before treatment, researchers used large-scale brain modeling to identify brain regions whose perturbation could shift a depressive brain state to a healthy one. The identified regions correlated with density maps of serotonin receptors 5-HT2a and 5-HT1a, where psilocin (psilocybin's active metabolite) acts as an agonist. These findings provide causal mechanistic evidence linking specific brain regions and serotonergic transmission to recovery from depression via psilocybin.
Research Square
September 20, 2022
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
10 citations
Psilocybin therapy for depression shows promise, but how it works is unclear. By comparing responders (those with >50% reduction in symptoms) to non-responders after 10mg and 25mg doses, whole-brain modeling identified specific brain regions whose dynamics shift from a depressive to a healthy state. These regions overlap with maps of serotonin 5-HT2A and 5-HT1A receptors, which psilocin—the active metabolite of psilocybin—activates. The findings provide causal evidence linking serotonergic transmission and recovery from depression via psilocybin.
bioRxiv (Cold Spring Harbor Laboratory)
July 25, 2018
Louis-David Lord, Paul Expert, Selen Atasoy et al.
10 citations
preprint
Brain activity can be viewed as exploring a landscape of different activity patterns over time, shifting between stable states of functional connectivity that support various mental processes. In a study using fMRI data from healthy participants given intravenous psilocybin (the active compound in magic mushrooms), researchers analyzed how this dynamical landscape changes during the psychedelic state. They found that a connectivity state linked to the fronto-parietal control system became strongly destabilized, while transitions toward a globally synchronized state increased. These changes suggest the psychedelic state biases the brain toward global integration at the cost of local network segregation, offering a mechanistic perspective on the subjective psychedelic experience and potential guidance for pharmacological interventions in neuropsychiatric disorders.
Oxford University Research Archive (ORA)
January 1, 2018
Louis-David Lord
The brain must balance integrating information across regions with segregating it into specialized modules. This thesis examines that balance in two altered states of consciousness: slow-wave sleep and the psychedelic experience from psilocybin. Using fMRI data, a novel method identifies highly integrative brain nodes based on persistent homology, which have high betweenness-centrality and participation coefficient but avoid dense clusters. Global synchrony and metastability decrease in slow-wave sleep while chimeraness increases; opposite effects occur under psilocybin. Psilocybin increases occurrence of a globally coherent functional connectivity state and decreases occupancy of a fronto-parietal control network.
Frontiers in network physiology
January 1, 2023
Louis-David Lord, Timoteo Carletti, Henrique Fernandes et al.
Normal waking consciousness requires a balance between global integration (long-distance brain interactions) and segregation (local processing). Altered states, such as anesthesia, tip this balance. Using electrocorticography (ECoG) in a monkey under ketamine or propofol anesthesia, the study examined band-specific synchronization across the whole brain and within localized clusters. Both anesthetics caused a loss of long-range integration in multiple frequency bands, most pronounced in beta (13-30 Hz) and low-gamma (30-80 Hz) bands, while local synchrony was strongly preserved in all bands. This demonstrates a shift away from the integration/segregation equilibrium at sub-second time scales.