The default-mode network (DMN)

“‘When michael pollan set out to research how lsd and psilocybin (the active ingredient in magic mushrooms) are being used to provide relief to people suffering from difficult-to-treat conditions such as depression, addiction and anxiety, he did not intend to write what is undoubtedly his most personal book. but upon discovering how these remarkable substances are improving the lives not only of the mentally ill but also of healthy people coming to grips with the challenges of everyday life, he decided to explore the landscape of the mind in the first person as well as the third. thus began a singular adventure into the experience of various altered states of consciousness, along with a dive deep into both the latest brain science and the thriving underground community of psychedelic therapists …’– prologue: a new door — a renaissance — natural history: bemushroomed — history: the first wave. part i: the promise ; part ii: the crack-up — travelogue: journeying underground. trip one: lsd ; trip two: psilocybin ; trip three: 5-meo-dmt (or, the toad) — the neuroscience: your brain on psychedelics — the trip treatment: psychedelics in psychotherapy. one: dying ; two: addiction ; three: depression ; coda: going to meet my default mode network — epilogue: in praise of neural diversity.”

“Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin–prodrug of the nonselective serotonin 2a receptor agonist and classic psychedelic psilocin. psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 hz in posterior association cortices, and from 8 to 100 hz in frontal association cortices. large decreases in oscillatory power were seen in areas of the default-mode network. independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-ht2a receptors. these findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-ht2a receptor-mediated excitation of deep pyramidal cells.”

“Psilocybin is a classic psychedelic and a candidate drug model of psychosis. this study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (fc) using functional magnetic resonance imaging (fmri). fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. primary analyses focused on changes in fc between the default-mode- (dmn) and task-positive network (tpn). spontaneous activity in the dmn is orthogonal to spontaneous activity in the tpn, and it is well known that these networks support very different functions (ie, the dmn supports introspection, whereas the tpn supports externally focused attention). here, independent components and seed-based fc analyses revealed increased dmn-tpn fc and so decreased dmn-tpn orthogonality after psilocybin. increased dmn-tpn fc has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. increased dmn-tpn fc has also been observed in sedation, as has decreased thalamocortical fc, but here we found preserved thalamocortical fc after psilocybin. thus, we propose that thalamocortical fc may be related to arousal, whereas dmn-tpn fc is related to the separateness of internally and externally focused states. we suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.”

“Peak experiences are moments of self-actualization, which may include mystical and transcendent elements. many cultures have incorporated psilocybin into religious rituals because of its ability to induce these experiences. research has established that peak experiences facilitated by psilocybin may have long-lasting effects, although set and setting are important determinants of both the content and the emotional tone of individual drug experiences. experimental research has demonstrated that psilocybin can induce peak experiences in controlled environments and these effects persist over the long term. the mechanisms through which psilocybin facilitates peak experiences involve blockage of 5-ht2areceptor sites, decoherence of cortical oscillations, and disruptions to ordinary functioning of the default-mode network.”

“Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. the psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of ‘primary states’ is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit ‘criticality,’ i.e., the property of being poised at a ‘critical’ point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. it is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. it is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (dmn) and a decoupling between the dmn and the medial temporal lobes (which are normally significantly coupled). these hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (rem) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state. © 2014 carhart-harris, leech, hellyer, shanahan, feilding, tagliazucchi, chialvo and nutt.”

“Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. here, cerebral blood flow (cbf) and blood oxygen-level dependent (bold) resting-state functional connectivity (rsfc) were measured with functional magnetic resonance imaging (fmri) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (trd). quality pre and post treatment fmri data were collected from 16 of 19 patients. decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. whole-brain analyses revealed post-treatment decreases in cbf in the temporal cortex, including the amygdala. decreased amygdala cbf correlated with reduced depressive symptoms. focusing on a priori selected circuitry for rsfc analyses, increased rsfc was observed within the default-mode network (dmn) post-treatment. increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex rsfc was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex rsfc. these data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. the post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. a ‘reset’ therapeutic mechanism is proposed.”

“The study of rapid changes in brain dynamics and functional connectivity (fc) is of increasing interest in neuroimaging. brain states departing from normal waking consciousness are expected to be accompanied by alterations in the aforementioned dynamics. in particular, the psychedelic experience produced by psilocybin (a substance found in magic mushrooms) is characterized by unconstrained cognition and profound alterations in the perception of time, space and selfhood. considering the spontaneous and subjective manifestation of these effects, we hypothesize that neural correlates of the psychedelic experience can be found in the dynamics and variability of spontaneous brain activity fluctuations and connectivity, measurable with functional magnetic resonance imaging (fmri). fifteen healthy subjects were scanned before, during and after intravenous infusion of psilocybin and an inert placebo. blood-oxygen level dependent (bold) temporal variability was assessed computing the variance and total spectral power, resulting in increased signal variability bilaterally in the hippocampi and anterior cingulate cortex. changes in bold signal spectral behavior (including spectral scaling exponents) affected exclusively higher brain systems such as the default mode, executive control and dorsal attention networks. a novel framework enabled us to track different connectivity states explored by the brain during rest. this approach revealed a wider repertoire of connectivity states post-psilocybin than during control conditions. together, the present results provide a comprehensive account of the effects of psilocybin on dynamical behaviour in the human brain at a macroscopic level and may have implications for our understanding of the unconstrained, hyper-associative quality of consciousness in the psychedelic state.”