Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

BACKGROUND: To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. METHODS: Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). RESULTS: DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. CONCLUSIONS: Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question.

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study.

MAIN OBJECTIVE: Disorders of consciousness (DOC; encompassing coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state minus/plus (MCS-/+)) are associated with structural brain injury. The extent of this damage remains poorly understood and merits a detailed examination using novel analysis techniques. Research design/methods and procedures: This study used voxel-based morphometry (VBM) on structural magnetic resonance imaging scans of 61 patients with DOC to examine grey and white matter injury associated with DOC, time spent in DOC, aetiology and diagnosis. MAIN OUTCOMES AND RESULTS: DOC and time spent in DOC were found to be associated with widespread structural brain injury, although the latter did not correlate strongly with injury in the right cerebral hemisphere. Traumatic, as compared to non-traumatic aetiology, was related to more injury in the brainstem, midbrain, thalamus, hypothalamus, basal forebrain, cerebellum, and posterior corpus callosum. Potential structural differences were found between VS/UWS and MCS and between MCS- and MCS+, but need further examination. CONCLUSIONS: The findings indicate that both traumatic and non-traumatic DOC are associated with widespread structural brain injury, although differences exist that could lead to aetiology-specific treatment strategies. Furthermore, the high degree of atrophy occurring after initial brain injury prompts the development and use of neuroprotective techniques to potentially increase patients' chances of recovery.

Propofol-Induced Frontal Cortex Disconnection: A Study of Resting-State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies.

Propofol is one of the most commonly used anesthetics in the world, but much remains unknown about the mechanisms by which it induces loss of consciousness. In this resting-state functional magnetic resonance imaging study, we examined qualitative and quantitative changes of resting-state networks (RSNs), total brain connectivity, and mean oscillation frequencies of the regional blood oxygenation level-dependent (BOLD) signal, associated with propofol-induced mild sedation and loss of responsiveness in healthy subjects. We found that detectability of RSNs diminished significantly with loss of responsiveness, and total brain connectivity decreased strongly in the frontal cortex, which was associated with increased mean oscillation frequencies of the BOLD signal. Our results suggest a pivotal role of the frontal cortex in propofol-induced loss of responsiveness.

Thalamus, brainstem and salience network connectivity changes during propofol-induced sedation and unconsciousness.

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness.