Acetylcholine and metacognition during sleep.

Acetylcholine is a neurotransmitter and neuromodulator involved in a variety of cognitive functions. Additionally, acetylcholine is involved in the regulation of REM sleep: cholinergic neurons in the brainstem and basal forebrain project to and innervate wide areas of the cerebral cortex, and reciprocally interact with other neuromodulatory systems, to produce the sleep-wake cycle and different sleep stages. Consciousness and cognition vary considerably across and within sleep stages, with metacognitive capacity being strikingly reduced even during aesthetically and emotionally rich dream experiences. A notable exception is the phenomenon of lucid dreaming-a rare state whereby waking levels of metacognitive awareness are restored during sleep-resulting in individuals becoming aware of the fact that they are dreaming. The role of neurotransmitters in these fluctuations of consciousness and cognition during sleep is still poorly understood. While recent studies using acetylcholinesterase inhibitors suggest a potential role of acetylcholine in the occurrence of lucid dreaming, the underlying mechanisms by which this effect is produced remains un-modelled and unknown; with the causal link between cholinergic mechanisms and upstream psychological states being complex and elusive. Several theories and approaches targeting the association between acetylcholine and metacognition during wakefulness and sleep are highlighted in this review, moving through microscopic, mesoscopic and macroscopic levels of analysis to detail this phenomenon at several organisational scales. Several exploratory hypotheses will be developed to guide future research towards fully articulating how metacognition is affected by activity at the acetylcholine receptor.

Minds and Brains, Sleep and Psychiatry.

OBJECTIVE: This article offers a philosophical thesis for psychiatric disorders that rests upon some simple truths about the mind and brain. Specifically, it asks whether the dual aspect monism-that emerges from sleep research and theoretical neurobiology-can be applied to pathophysiology and psychopathology in psychiatry. METHODS: Our starting point is that the mind and brain are emergent aspects of the same (neuronal) dynamics; namely, the brain-mind. Our endpoint is that synaptic dysconnection syndromes inherit the same dual aspect; namely, aberrant inference or belief updating on the one hand, and a failure of neuromodulatory synaptic gain control on the other. We start with some basic considerations from sleep research that integrate the phenomenology of dreaming with the neurophysiology of sleep. RESULTS: We then leverage this treatment by treating the brain as an organ of inference. Our particular focus is on the role of precision (i.e., the representation of uncertainty) in belief updating and the accompanying synaptic mechanisms. CONCLUSIONS: Finally, we suggest a dual aspect approach-based upon belief updating (i.e., mind processes) and its neurophysiological implementation (i.e., brain processes)-has a wide explanatory compass for psychiatry and various movement disorders. This approach identifies the kind of pathophysiology that underwrites psychopathology-and points to certain psychotherapeutic and psychopharmacological targets, which may stand in mechanistic relation to each other.

Towards a Functional Understanding of PGO Waves.

Ponto-Geniculo-Occipital (PGO) waves are biphasic field potentials identified in a range of mammalian species that are ubiquitous with sleep, but can also be identified in waking perception and eye movement. Their role in REM sleep and visual perception more broadly may constitute a promising avenue for further research, however what was once an active field of study has recently fallen into stasis. With the reality that invasive recordings performed on animals cannot be replicated in humans; while animals themselves cannot convey experience to the extent required to elucidate how PGO waves factor into awareness and behavior, innovative solutions are required if significant research outcomes are to ever be realized. Advances in non-invasive imaging technologies and sophistication in imaging methods now offer substantial scope to renew the study of the electrophysiological substrates of waking and dreaming perception. Among these, Magnetoencephalogram (MEG) stands out through its capacity to measure deep brain activations with high temporal resolution. With the current trend in sleep and dream research to produce translational findings of psychopathological and medical significance, in addition to the clear links that PGO wave generation sites share, pharmacologically, with receptors involved in expression of mental illness; there is a strong case to support scientific research into PGO waves and develop a functional understanding of their broader role in human perception.