A default mode of brain function in altered states of consciousness

in Archives Italiennes de Biologie (2012), 150(2-3), 107-121

Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.

in PLoS ONE (2012), 7(1), 29072

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]

Metabolic activity in external and internal awareness networks in severely brain-damaged patients.

in Journal of Rehabilitation Medicine (2012), 44(6), 487-94

OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been ... [more ▼]

OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside. [less ▲]

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

in Archives Italiennes de Biologie (2012), 150(2-3), 107-21

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 ... [more ▼]

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. [less ▲]

Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.

in Journal of Neurology (2012), 259(6), 1087-98

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this ... [more ▼]

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 +/- 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 +/- 19 years; 4 traumatic; 21 +/- 23 months post injury) and 14 MCS+ (aged 43 +/- 19 years; 5 traumatic; 19 +/- 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. [less ▲]

Brain connectivity in disorders of consciousness.

in Brain connectivity (2012), 2(1), 1-10

The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest ... [more ▼]

The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patients. In this context, particular attention has been devoted to connectivity studies-as these, more than measures of brain metabolism, may be more appropriate to capture the dynamics of large populations of neurons. Here, we will review the pros and cons of various connectivity methods as potential diagnostic tools in brain-damaged patients with DOC. We will also discuss the relevance of the study of the level versus the contents of consciousness in this context. [less ▲]

Granger Causality Analysis of Steady-State Electroencephalographic Signals during Propofol-Induced Anaesthesia

in PLoS ONE (2012), 7(1),

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as ‘integrated information’ and ‘causal density’. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]

Propofol anesthesia and sleep: a high-density EEG study.

in Sleep (2011), 34(3), 283-91

STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical ... [more ▼]

STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep. DESIGN: 256-channel EEG recordings in humans during propofol anesthesia. SETTING: Hospital operating room. PATIENTS OR PARTICIPANTS: 8 healthy subjects (4 males) INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Initially, propofol induced increases in EEG power from 12-25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25-40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness. CONCLUSIONS: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity. CITATION: Murphy M; Bruno MA; Riedner BA; Boveroux P; Noirhomme Q; Landsness EC; Brichant JF; Phillips C; Massimini M; Laureys S; Tononi G; Boly M. Propofol anesthesia and sleep: a high-density EEG study. SLEEP 2011;34(3):283-291. [less ▲]

La neuro-imagerie: un outil diagnostique des etats de conscience alteree.

in Medecine Sciences : M/S (2011), 27(1), 77-81

Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of ... [more ▼]

Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of fronto-parietal network, or the spontaneous activity in resting state have been shown to be helpful to disentangle vegetative from minimally conscious patients. Active neuroimagery paradigms also allow detecting voluntary and conscious activity in non-communicative patients. The implementation of these methods in clinical routine could permit to reduce the current high rate of misdiagnosis (40%). [less ▲]

Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state.

in Brain : A Journal of Neurology (2011), 134(Pt 8), 2222-32

The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate ... [more ▼]

The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate patients in a vegetative state from patients in a minimally conscious state. Using high-density electroencephalographic sleep recordings, 11 patients with disorders of consciousness (six in a minimally conscious state, five in a vegetative state) were studied to correlate the electrophysiological changes associated with sleep to behavioural changes in vigilance (sustained eye closure and muscle inactivity). All minimally conscious patients showed clear electroencephalographic changes associated with decreases in behavioural vigilance. In the five minimally conscious patients showing sustained behavioural sleep periods, we identified several electrophysiological characteristics typical of normal sleep. In particular, all minimally conscious patients showed an alternating non-rapid eye movement/rapid eye movement sleep pattern and a homoeostatic decline of electroencephalographic slow wave activity through the night. In contrast, for most patients in a vegetative state, while preserved behavioural sleep was observed, the electroencephalographic patterns remained virtually unchanged during periods with the eyes closed compared to periods of behavioural wakefulness (eyes open and muscle activity). No slow wave sleep or rapid eye movement sleep stages could be identified and no homoeostatic regulation of sleep-related slow wave activity was observed over the night-time period. In conclusion, we observed behavioural, but no electrophysiological, sleep wake patterns in patients in a vegetative state, while there were near-to-normal patterns of sleep in patients in a minimally conscious state. These results shed light on the relationship between sleep electrophysiology and the level of consciousness in severely brain-damaged patients. We suggest that the study of sleep and homoeostatic regulation of slow wave activity may provide a complementary tool for the assessment of brain function in minimally conscious state and vegetative state patients. [less ▲]