http://people.csail.mit.edu/ythomas/publications/2015SleepDeprivation-NeuroImage.pdf

Functional connectivity during rested wakefulness predicts vulnerability to sleep deprivation.

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico–striato–thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

https://www.pnas.org/content/pnas/116/7/2743.full.pdf

Effective connectivity changes in LSD-induced altered states of consciousness in humans

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo- cortical functional connectivity is sufficient to produce unconsciousness.

/pdf/disruption-of-thalamic-functional-connectivity-is-a-neural-2f5o76e8w5.pdf

Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

How general anesthetics cause loss of consciousness is unknown Some evidence points toward effects on the neocortex causing “top-down” inhibition, whereas other findings suggest that these drugs act via subcortical mechanisms, possibly selectively stimulating networks promoting natural sleep To determine whether some neuronal circuits are affected before others, we used Morlet wavelet analysis to obtain high temporal resolution in the time-varying power spectra of local field potentials recorded simultaneously in discrete brain regions at natural sleep onset and during anesthetic-induced loss of righting reflex in rats Although we observed changes in the local field potentials that were anesthetic-specific, there were some common changes in high-frequency (20–40 Hz) oscillations (reductions in frequency and increases in power) that could be detected at, or before, sleep onset and anesthetic-induced loss of righting reflex For propofol and natural sleep, these changes occur first in the thalamus before changes could be detected in the neocortex With dexmedetomidine, the changes occurred simultaneously in the thalamus and neocortex In addition, the phase relationships between the low-frequency (1–4 Hz) oscillations in thalamic nuclei and neocortical areas are essentially the same for natural sleep and following dexmedetomidine administration, but a sudden change in phase, attributable to an effect in the central medial thalamus, occurs at the point of dexmedetomidine loss of righting reflex Our data are consistent with the central medial thalamus acting as a key hub through which general anesthesia and natural sleep are initiated

https://www.jneurosci.org/content/jneuro/34/40/13326.full.pdf

Altered Activity in the Central Medial Thalamus Precedes Changes in the Neocortex during Transitions into Both Sleep and Propofol Anesthesia

This final chapter provides the reader with an overview of the neurological and neurobiological literature on the neural substrate of consciousness. First, the chapter reviews the evidence suggesting that consciousness can be dissociated from other brain functions, such as responsiveness to sensory inputs, motor control, attention, language, memory, reflection, spatial frames of reference, the body, and perhaps even the self. The chapter then summarizes what has been learned by studying global changes in the level of consciousness, such as sleep, anesthesia, seizures, and post-comatose states. Next, it asks what can be said at this point about the neuroanatomy and the neurophysiology of consciousness. The chapter ends by briefly considering how a theoretical analysis of the fundamental properties of consciousness can complement neurobiological studies.

The Neurology of Consciousness: An Overview

Study objectives To determine whether thalamocortical signaling between the thalamus and the neocortex decreases from wakefulness to nonrapid eye movement (NREM) sleep. Design Electroencephalography and functional magnetic resonance imaging data were collected simultaneously at 02:30 after 44 h of sleep deprivation. Setting Clinical research hospital. Participants There were six volunteers (mean age 24.2 y, one male) who yielded sufficient amounts of usable, artifact-free data. All were healthy, right-handed native English speakers who consumed less than 710 mL of caffeinated beverages per day. Psychiatric, neurological, circadian, and sleep disorders were ruled out by reviewing each patient's clinical history. A standard clinical nocturnal polysomnogram was negative for sleep disorders. Interventions N/A. Measurements and results A functional connectivity analysis was performed using the centromedian nucleus as the seed region. We determined the statistical significance of the difference between correlations obtained during wakefulness and during slow wave sleep. Neocortical regions displaying decreased thalamic connectivity were all heteromodal regions (e.g., medial frontal gyrus and posterior cingulate/precuneus), whereas there was a complete absence of neocortical regions displaying increased thalamic connectivity. Although more clusters of significant decreases were observed in stage 2 sleep, these results were similar to the results for slow wave sleep. Conclusions Results of this study provide evidence of a functional deafferentation of the neocortex during nonrapid eye movement (NREM) sleep in humans. This deafferentation likely accounts for increased sensory awareness thresholds during NREM sleep. Decreased thalamocortical connectivity in regions such as the posterior cingulate/precuneus also are observed in coma and general anesthesia, suggesting that changes in thalamocortical connectivity may act as a universal "control switch" for changes in consciousness that are observed in coma, general anesthesia, and natural sleep.

Morgan L Pixa

Papers

Decreased connectivity between the thalamus and the neocortex during human nonrapid eye movement sleep.