Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be...
Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as...
Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with...
Nature CommunicationsApril 26, 2022David E. Melnikoff, Ryan W. Carlson, Paul E. Stillman
Flow is a subjective state characterized by immersion and engagement in one’s current activity. The benefits of flow for productivity and health are well-documented, but a rigorous description of the flow-generating process remains elusive. Here we develop and empirically test a theory of flow’s computational substrates: the informational theory of flow. Our theory draws on the concept of...
Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of consciousness. We employ electroencephalographic (EEG)...
Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants...
A fundamental scientific question concerns the neural basis of perceptual consciousness and perceptual monitoring resulting from the processing of sensory events. Although recent studies identified neurons reflecting stimulus visibility, their functional role remains unknown. Here, we show that perceptual consciousness and monitoring involve evidence accumulation. We recorded single-neuron...
An outstanding challenge for consciousness research is to characterize the neural signature of conscious access independently of any decisional processes. Here we present a model-based approach that uses inter-trial variability to identify the brain dynamics associated with stimulus processing. We demonstrate that, even in the absence of any task or behavior, the electroencephalographic...
Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine's dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective...
In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) - which are experienced as involuntary - according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353...
Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to...
When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in...
The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([18F]florbetapir tracer for Aβ and [18F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ aggregation within the brain’s default mode network leads to regional hypometabolism in distant but...
A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST)...
The default mode network (DMN) is associated with a wide range of brain functions. In humans, the DMN is marked by strong functional connectivity among three core regions: medial prefrontal cortex (mPFC), posterior parietal cortex (PPC), and the medial parietal and posterior cingulate cortex (PCC). Neuroimaging studies have shown that the DMN also exists in non-human primates, suggesting that...
The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange...
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes,...
Humans are typically unable to engage in sustained smooth pursuit for imagined objects. However, it is unknown to what extent smooth tracking occurs for visual imagery during REM sleep dreaming. Here we examine smooth pursuit eye movements during tracking of a slow-moving visual target during lucid dreams in REM sleep. Highly similar smooth pursuit tracking was observed during both waking...
Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at...
Does the default mode network (DMN) reconfigure to encode information about the changing environment? This question has proven difficult, because patterns of functional connectivity reflect a mixture of stimulus-induced neural processes, intrinsic neural processes and non-neuronal noise. Here we introduce inter-subject functional correlation (ISFC), which isolates stimulus-dependent...
A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the...