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Neuroscience. 2018 Jul 1;382:115-124. doi: 10.1016/j.neuroscience.2018.04.039.

Disrupted Interactions Between Arousal and Cortical Awareness Networks in MCS and VS/UWS Patients: Evidence from Resting-state Functional Imaging Connectivity.

Author information

1
Cognitive and Mental Health Research Center, Beijing Institute of Basic Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing 100850, China.
2
Department of Radiology, Army General Hospital, No. 5 Nan Men Cang, East Si Shi Tiao, Dongcheng District, Beijing 100700, China. Electronic address: bei925@sina.com.
3
Department of Radiology, Army General Hospital, No. 5 Nan Men Cang, East Si Shi Tiao, Dongcheng District, Beijing 100700, China.
4
Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
5
Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: xiliu@mcw.edu.
6
Cognitive and Mental Health Research Center, Beijing Institute of Basic Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing 100850, China. Electronic address: yangz236@163.com.

Abstract

Clinical patients in a vegetative state or unresponsive wakefulness syndrome (VS/UWS) demonstrate distinct arousal-awareness dissociation; the neuropathological mechanisms underlying such dissociation remain poorly understood. Here, we systematically examined how functional connectivity from the brainstem areas regulating arousal to the cortical networks supporting internal and external awareness is disrupted in minimally conscious state (MCS) and VS/UWS patients. Resting-state functional imaging was conducted in 23 MCS patients, 31 VS/UWS patients, and 20 age-matched healthy individuals. A hierarchical cluster analysis was conducted using all voxel-based signals in the brainstem to identify the specific areas for arousal. We found that the pontine tegmentum area (PTA) and caudal midbrain area persistently formed a distinct cluster that exclusively showed extensive connections with the cortical networks supporting internal and external awareness in healthy individuals, confirming their role in arousal. We show that functional connectivity from the PTA and caudal midbrain area to the cortical-awareness-supporting networks were significantly reduced in MCS and VS/UWS patients; importantly, as the clinical symptoms of consciousness disorders deepen from MCS to VS/UWS, functional connectivity strength became significantly reduced, changing from presenting no significant connections in MCS to widespread negative connections in VS/UWS. Additionally, we observed increased connectivity from the PTA and caudal midbrain area to limbic structures, the brainstem areas, and the cerebellum in MCS and VS/UWS patients, consistent with prior studies. These findings offer important insights into the neural network mechanisms underlying the long-observed arousal-awareness dissociation in VS/UWS patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.

KEYWORDS:

arousal; functional connectivity; internal and external awareness; minimally conscious state (MCS); resting-state fMRI; vegetative state/unresponsive wakefulness syndrome (VS/UWS)

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