The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained 'rest' when activity in the brain is 'free-wheeling'. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer's disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer's disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region's function (the 'Arousal, Balance and Breadth of Attention' model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by 'tuning' whole-brain metastability and so adjusts how stable brain network activity is over time.

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.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen leveldependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.is a potent serotonergic hallucinogen or "psychedelic" that alters consciousness in a profound and characteristic way. First synthesized in 1938, its extraordinary psychological properties were not discovered until 1943 (1). LSD would go on to have a major effect on psychology and psychiatry in the 1950s and 1960s; however, increasing recreational use and its influence on youth culture provoked the drug's being made illegal in the late 1960s. As a consequence, human research with LSD has been on pause for half a century. However, inspired by a revival of research with other psychedelics, such as psilocybin and ayahuasca, a small number of new reports on the psychological effects of LSD have recently been published (2-6).LSD has a high affinity for a range of different neurotransmitter receptors, but its characteristic psychological effects are thought to be mediated by serotonin 2A receptor (5-HT 2A R) agonism (7). Previous neurophysiological research with LSD is limited to electroencephalography (EEG) studies in the 1950s and 1960s. These reported reductions in oscillatory power, predominantly in the lower-frequency bands, and an increase i...

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen leveldependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/ functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.receptor P silocybin is the prodrug of psilocin (4-hydroxy-dimethyltryptamine), the primary hallucinogenic component of magic mushrooms, and a classic psychedelic ("mind-manifesting") drug. Psilocybin has been used for centuries in healing ceremonies (1) and more recently in psychotherapy (2); it is capable of stimulating profound existential experiences (3), which can leave a lasting psychological impression (4). However, despite a wealth of literature on its phenomenology, we currently know very little about how its effects are produced in the brain. The present study sought to address this question using complementary functional MRI (fMRI) techniques and a protocol designed to image the transition from normal waking consciousness to the psychedelic state. Two groups of healthy subjects were scanned using arterial spin labeling (ASL) perfusion and blood-oxygen level-dependent (BOLD) fMRI during intravenous infusion of psilocybin. Infused over 60 s (2 mg in 10-mL saline), psilocybin's subjective effects begin within seconds (5), allowing the capture of the corresponding change in brain state.Results ASL Perfusion fMRI. Fifteen healthy, hallucinogen-experienced subjects (five females), mean age 34.1 (SD 8.2) were scanned with ASL. Subjects underwent an anatomical scan followed by two taskfree functional scans, each lasting 18 min. Subjects were instructed to relax and a fixation cross was displayed. Solutions were inf...