Default Mode Network Modulation by Psychedelics: A Systematic Review

Abstract

Psychedelics are a unique class of drug which commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterised by increased temporal coherence at rest have been termed the ‘Default Mode Network’ (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), schizophrenia and obsessive-compulsive disorder (OCD). To date, a number of studies have investigated how psychedelics modulate this network, but no comprehensive review has critically evaluated how major classical psychedelic agents - Lysergic Acid Diethylamide (LSD), psilocybin, and ayahuasca - modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research forward in such a way that the neurocognitive mechanisms of psychedelics can be further elucidated.

Evolving antidepressant: from SSRIs to psychedelic

“…Consistent evidence was found that psychedelics reduce DMN connectivity, particularly in prefrontal cortex, a crucial node of DMN [5]. This reduction in DMN connectivity is associated with increased connectivity between the DMN and other brain networks, such as the salience and executive control networks, which are involved in emotion regulation and cognitive flexibility [6]. propose that the modulation of the DMN by psychedelics is mediated by the activation of serotonin 2A receptors in the cortex, leading to increased excitability and plasticity of neural networks.…”

The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

“…Additionally, we found that in psilocybin subjects the distribution of idiosyncrasy was systematically shifted, and in particular shifted away from FPN and towards DMN regions. Intriguingly, the DMN is assumed to play a key role in mediating the subjective effects of psilocybin and psychedelics more generally 42 . This assumption is backed by a large body of evidence including the 5-HT2AR expression profile of the DMN 23 and the consistent observation that its activity and connectivity is significantly altered during acute psychedelic states 24,27,43,44 .…”

Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.

“…Recent resting-state fMRI studies in humans have indirectly assessed the effects of psychedelic agents with brain-wide coverage [14][15][16][17][18][19][20][21][22][23][24][25]. Notwithstanding some preprocessing-dependent inconsistencies [139,141], the consensus is that psilocybin reduces functional connectivity within association networks, particularly within the default mode network [14,[23][24][25]142]. This effect has been hypothesized to reflect the subjective experience of ego dissolution [11,16,27,29].…”