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The self and its resting state in consciousness: an investigation of the vegetative state.

ABSTRACT: Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting-state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting-state activity, that is functional connectivity and the amplitude of low-frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self-referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness.

SUBMITTER: Huang Z

PROVIDER: S-EPMC6868996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A severe brain injury may lead to a disorder of consciousness (DOC) such as coma, vegetative state (VS), minimally conscious state (MCS) or locked-in syndrome (LIS). Till date, the diagnosis of DOC relies only on clinical evaluation or subjective scoring systems such as Glasgow coma scale, which fails to detect subtle changes and thereby results in diagnostic errors. The high rate of misdiagnosis and inability to predict the recovery of consciousness for DOC patients have created a huge research interest in the assessment of consciousness. Researchers have explored the use of various stimulation and neuroimaging techniques to improve the diagnosis. In this article, we present the important findings of resting-state as well as sensory stimulation methods and highlight the stimuli proven to be successful in the assessment of consciousness. Primarily, we review the literature based on (a) application/non-use of stimuli (i.e., sensory stimulation/resting state-based), (b) type of stimulation used (i.e., auditory, visual, tactile, olfactory, or mental-imagery), (c) electrophysiological signal used (EEG/ERP, fMRI, PET, EMG, SCL, or ECG). Among the sensory stimulation methods, auditory stimulation has been extensively used, since it is easier to conduct for these patients. Olfactory and tactile stimulation have been less explored and need further research. Emotionally charged stimuli such as subject's own name or narratives in a familiar voice or subject's own face/family pictures or music result in stronger responses than neutral stimuli. Studies based on resting state analysis have employed measures like complexity, power spectral features, entropy and functional connectivity patterns to distinguish between the VS and MCS patients. Resting-state EEG and fMRI are the state-of-the-art techniques and have a huge potential in predicting the recovery of coma patients. Further, EMG and mental-imagery based studies attempt to obtain volitional responses from the VS patients and thus could detect their command-following capability. This may provide an effective means to communicate with these patients. Recent studies have employed fMRI and PET to understand the brain-activation patterns corresponding to the mental imagery. This review promotes our knowledge about the techniques used for the diagnosis of patients with DOC and attempts to provide ideas for future research.

Project description:BackgroundRecent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations.MethodsResting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters?=?8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness.ResultsThe current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area).ConclusionIn conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness.

Project description:Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment.

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The self and its resting state in consciousness: an investigation of the vegetative state.

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