Brain functional connectivity differentiates dexmedetomidine from propofol and natural sleep.

BACKGROUND: We used functional connectivity measures from brain resting state functional magnetic resonance imaging to identify human neural correlates of sedation with dexmedetomidine or propofol and their similarities with natural sleep. METHODS: Connectivity within the resting state networks that are proposed to sustain consciousness generation was compared between deep non-rapid-eye-movement (N3) sleep, dexmedetomidine sedation, and propofol sedation in volunteers who became unresponsive to verbal command. A newly acquired dexmedetomidine dataset was compared with our previously published propofol and N3 sleep datasets. RESULTS: In all three unresponsive states (dexmedetomidine sedation, propofol sedation, and N3 sleep), within-network functional connectivity, including thalamic functional connectivity in the higher-order (default mode, executive control, and salience) networks, was significantly reduced as compared with the wake state. Thalamic functional connectivity was not reduced for unresponsive states within lower-order (auditory, sensorimotor, and visual) networks. Voxel-wise statistical comparisons between the different unresponsive states revealed that thalamic functional connectivity with the medial prefrontal/anterior cingulate cortex and with the mesopontine area was reduced least during dexmedetomidine-induced unresponsiveness and most during propofol-induced unresponsiveness. The reduction seen during N3 sleep was intermediate between those of dexmedetomidine and propofol. CONCLUSIONS: Thalamic connectivity with key nodes of arousal and saliency detection networks was relatively preserved during N3 sleep and dexmedetomidine-induced unresponsiveness as compared to propofol. These network effects may explain the rapid recovery of oriented responsiveness to external stimulation seen under dexmedetomidine sedation. TRIAL REGISTRY NUMBER: Committee number: 'Comité d'Ethique Hospitalo-Facultaire Universitaire de Liège' (707); EudraCT number: 2012-003562-40; internal reference: 20121/135; accepted on August 31, 2012; Chair: Prof G. Rorive. As it was considered a phase I clinical trial, this protocol does not appear on the EudraCT public website.

A default mode of brain function in altered states of consciousness.

Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of neuronal assemblies have been found to show synchronized oscillatory activity behavior and are said to be functionally connected. One of the most robust of these is the default mode network, which is associated with intrinsic processes like mind wandering and self-projection. Furthermore, activity in this network is anticorrelated with activity in a network that is linked to attention to external stimuli. The integrity of both networks is disturbed in altered states of consciousness, like sleep, general anesthesia and hypnosis. In coma and related disorders of consciousness, encompassing the vegetative state (unresponsive wakefulness syndrome) and minimally conscious state, default mode network integrity correlates with the level of remaining consciousness, offering the possibility of using this information for diagnostic and prognostic purposes. Functional brain imaging is currently being validated as a valuable addition to the standardized behavioral assessments that are already in use.

Mindsight: diagnostics in disorders of consciousness.

Diagnosis of patients with disorders of consciousness (comprising coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state) has long been dependent on unstandardized behavioral tests. The arrival of standardized behavioral tools, and especially the Coma Recovery Scale revised, uncovered a high rate of misdiagnosis. Ancillary techniques, such as brain imaging and electrophysiological examinations, are ever more often being deployed to aid in the search for remaining consciousness. They are used to look for brain activity patterns similar to those found in healthy controls. The development of portable and cheaper devices will make these techniques more widely available.