Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol.
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ABSTRACT:
SUBMITTER: Huang Z
PROVIDER: S-EPMC6123455 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol.
Huang Zirui Z Vlisides Phillip E PE Tarnal Vijaykumar C VC Janke Ellen L EL Keefe Kelley M KM Collins Margaret M MM McKinney Amy M AM Picton Paul P Harris Richard E RE Mashour George A GA Hudetz Anthony G AG
Scientific reports 20180904 1
Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMR ...[more]
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Project description:BackgroundThe wakeful brain can easily access and coordinate a large repertoire of different states-dynamics suggestive of "criticality." Anesthesia causes loss of criticality at the level of electroencephalogram waveforms, but the criticality of brain network connectivity is less well studied. The authors hypothesized that propofol anesthesia is associated with abrupt and divergent changes in brain network connectivity for different frequencies and time scales-characteristic of a phase transition, a signature of loss of criticality.MethodsAs part of a previously reported study, 16 volunteers were given propofol in slowly increasing brain concentrations, and their behavioral responsiveness was assessed. The network dynamics from 31-channel electroencephalogram data were calculated from 1 to 20 Hz using four phase and envelope amplitude-based functional connectivity metrics that covered a wide range of time scales from milliseconds to minutes. The authors calculated network global efficiency, clustering coefficient, and statistical complexity (using the Jensen-Shannon divergence) for each functional connectivity metric and compared their findings with those from an in silico Kuramoto network model.ResultsThe transition to anesthesia was associated with critical slowing and then abrupt profound decreases in global network efficiency of 2 Hz power envelope metrics (from mean ± SD of 0.64 ± 0.15 to 0.29 ± 0.28 absolute value, P < 0.001, for medium; and from 0.47 ± 0.13 to 0.24 ± 0.21, P < 0.001, for long time scales) but with an increase in global network efficiency for 10 Hz weighted phase lag index (from 0.30 ± 0.20 to 0.72 ± 0.06, P < 0.001). Network complexity decreased for both the 10 Hz hypersynchronous (0.44 ± 0.13 to 0.23 ± 0.08, P < 0.001), and the 2 Hz asynchronous (0.73 ± 0.08 to 0.40 ± 0.13, P < 0.001) network states. These patterns of network coupling were consistent with those of the Kuramoto model of an order-disorder phase transition.ConclusionsAround loss of behavioral responsiveness, a small increase in propofol concentrations caused a collapse of long time scale power envelope connectivity and an increase in 10 Hz phase-based connectivity-suggestive of a brain network phase transition.Editor’s perspective
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Project description:Accurately measuring the neural correlates of consciousness is a grand challenge for neuroscience. Despite theoretical advances, developing reliable brain measures to track the loss of reportable consciousness during sedation is hampered by significant individual variability in susceptibility to anaesthetics. We addressed this challenge using high-density electroencephalography to characterise changes in brain networks during propofol sedation. Assessments of spectral connectivity networks before, during and after sedation were combined with measurements of behavioural responsiveness and drug concentrations in blood. Strikingly, we found that participants who had weaker alpha band networks at baseline were more likely to become unresponsive during sedation, despite registering similar levels of drug in blood. In contrast, phase-amplitude coupling between slow and alpha oscillations correlated with drug concentrations in blood. Our findings highlight novel markers that prognosticate individual differences in susceptibility to propofol and track drug exposure. These advances could inform accurate drug titration and brain state monitoring during anaesthesia.
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Project description:Reliable electroencephalography (EEG) signatures of transitions between consciousness and unconsciousness under anaesthesia have not yet been identified. Herein we examined network changes using graph theoretical analysis of high-density EEG during patient-titrated propofol-induced sedation. Responsiveness was used as a surrogate for consciousness. We divided the data into five states: baseline, transition into unresponsiveness, unresponsiveness, transition into responsiveness, and recovery. Power spectral analysis showed that delta power increased from responsiveness to unresponsiveness. In unresponsiveness, delta waves propagated from frontal to parietal regions as a traveling wave. Local increases in delta connectivity were evident in parietal but not frontal regions. Graph theory analysis showed that increased local efficiency could differentiate the levels of responsiveness. Interestingly, during transitions of responsive states, increased beta connectivity was noted relative to consciousness and unconsciousness, again with increased local efficiency. Abrupt network changes are evident in the transitions in responsiveness, with increased beta band power/connectivity marking transitions between responsive states, while the delta power/connectivity changes were consistent with the fading of consciousness using its surrogate responsiveness. These results provide novel insights into the neural correlates of these behavioural transitions and EEG signatures for monitoring the levels of consciousness under sedation.
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Project description:The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity has been defined in many ways by multiple different fields: here, we investigate measures of algorithmic and process complexity in both the temporal and topological domains, testing them on functional MRI BOLD signal data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, replicating our results in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of "overall complexity" of our data. This overall complexity was also able to discriminate between levels of sedation and serum concentrations of propofol, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.
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Project description:BackgroundImpaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.MethodsEight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time-frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions.ResultsSensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni corrected).ConclusionsPropofol-induced loss of consciousness is associated with impaired hierarchical feedforward connectivity assessed by EEG after occipital TMS.
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Project description:General anesthesia (GA) is a reversible manipulation of consciousness whose mechanism is mysterious at the level of neural networks leaving space for several competing hypotheses. We recorded electrocorticography (ECoG) signals in patients who underwent intracranial monitoring during awake surgery for the treatment of cerebral tumors in functional areas of the brain. Therefore, we recorded the transition from unconsciousness to consciousness directly on the brain surface. Using frequency resolved interferometry; we studied the intermediate ECoG frequencies (4-40 Hz). In the theoretical study, we used a computational Jansen and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we found that f increased by a factor equal to 1.62 ± 0.09, and δf varied by the same factor (1.61 ± 0.09) suggesting the existence of a scaling factor. We accelerated the time course of an unconscious EEG trace by an approximate factor 1.6 and we showed that the resulting EEG trace match the conscious state. Using the theoretical model, we successfully reproduced this behavior. We show that the recovery of consciousness corresponds to a transition in the frequency (f, δf) space, which is exactly reproduced by a simple time rescaling. These findings may perhaps be applied to other altered consciousness states.
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Project description:BackgroundAnaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level.MethodsWe compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings.ResultsMost subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state.ConclusionsAnaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content.Clinical trial registrationClinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004).
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Project description:Self-similarity is ubiquitous throughout natural phenomena, including the human brain. Recent evidence indicates that fractal dimension of functional brain networks, a measure of self-similarity, is diminished in patients diagnosed with disorders of consciousness arising from severe brain injury. Here, we set out to investigate whether loss of self-similarity is observed in the structural connectome of patients with disorders of consciousness. Using diffusion MRI tractography from N = 11 patients in a minimally conscious state (MCS), N = 10 patients diagnosed with unresponsive wakefulness syndrome (UWS), and N = 20 healthy controls, we show that fractal dimension of structural brain networks is diminished in DOC patients. Remarkably, we also show that fractal dimension of structural brain networks is preserved in patients who exhibit evidence of covert consciousness by performing mental imagery tasks during functional MRI scanning. These results demonstrate that differences in fractal dimension of structural brain networks are quantitatively associated with chronic loss of consciousness induced by severe brain injury, highlighting the close connection between structural organisation of the human brain and its ability to support cognitive function.
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2022-09-29 | GSE214208 | GEO