Effective Connectivity of Functionally Anticorrelated Networks Under Lysergic Acid Diethylamide

Background: Classic psychedelic-induced ego dissolution involves a shift in the sense of self and a blurring of the boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated with the balance of anticorrelated activity between the default mode network, which directs attention inward, and the salience network, which recruits the dorsal attention network to direct attention outward. Methods: To test whether changes in anticorrelated networks underlie the peak effects of lysergic acid diethylamide (LSD), we applied dynamic causal modeling to infer effective connectivity of resting-state functional magnetic resonance imaging scans from a study of 25 healthy adults who were administered 100 μg of LSD or placebo. Results: We found that inhibitory effective connectivity from the salience network to the default mode network became excitatory, and inhibitory effective connectivity from the default mode network to the dorsal attention network decreased under the peak effect of LSD. Conclusions: The effective connectivity changes we identified may reflect diminution of the functional anticorrelation between resting-state networks that may be a key neural mechanism of LSD and underlie ego dissolution. Our findings suggest that changes to the sense of self and subject-object boundaries across different states of consciousness may depend upon the organized balance of effective connectivity of resting-state networks

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organisation and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics; in particular, their influence on selfhood and subject-object boundaries—known as ego dissolution—surmised to underwrite their subjective and therapeutic effects. Agonist of 5HT2A receptors, located at the apex of the cortical hierarchy may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half life, suggesting that psychedelics may have long-term effects on neural plasticity – that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a surrender of ego resistance that increases the repertoire of perceptual hypotheses, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world—and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging

Neural Mechanisms of Resting-State Networks and the Amygdala underlying the Cognitive and Emotional Effects of Psilocybin

Background: Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesised to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood. Methods: We used functional MRI resting state images collected during a randomised, double-blinded, placebo-controlled clinical trial of 24 healthy adults under 0.2mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and three large-scale resting-state networks involved in cognition. These networks are the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Results: We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the DMN and SN however increased within the CEN. These changes in effective connectivity were statistically associated with behavioural measures of altered cognition and emotion under the influence of psilocybin. Conclusions: Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to RSN network connectivity. These changes are significant for altered cognition and perception and suggests targets for research investigating the efficacy of psychedelic therapy for internalising psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organisation using effective using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences