Murielle Kirsch

Resting state networks and consciousness Alterations of multiple resting state network connectivity in physiological, pharmacological and pathological consciousness states

In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI) functional connectivity under physiological (sleep), pharmacological (anesthesia), and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed resting state networks were the DMN, left and right executive control, salience, sensorimotor, auditory, and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this “lesion” approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients.

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.

What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology—thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development.

Mapping the functional connectome traits of levels of consciousness

Abstract Examining task‐free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data‐driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC‐traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task‐free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC‐traits were identified and linked to consciousness‐related clinical features. The first one represents the functional configuration of a “resting” human brain, and it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC‐trait reflects the disconnection of the visual and sensory‐motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC‐trait isolates the connectivity pattern encompassing the fronto‐parietal and the default‐mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC‐trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional sub‐circuits that get disrupted in severe brain‐damage.

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.

Impact of the addition of sufentanil 5 μg or clonidine 75 μg on the minimum local analgesic concentration of ropivacaine for epidural analgesia in labour: a randomized comparison

BACKGROUND Addition of lipophilic opioids or alpha2-agonists to local anaesthetic solutions reduces local anaesthetic requirements and side effects. While the efficacy and side effects of these adjuvants are dose-related, information about their relative analgesic potencies is lacking, making it difficult to draw meaningful clinical conclusions. The aim of the present study was to assess the relative sparing of ropivacaine by clinically relevant doses of sufentanil and clonidine using the minimum local analgesic concentration (MLAC) model. METHODS In this prospective, double-blind study, the sparing effect of sufentanil 5 microg and clonidine 75 microg on the MLAC of ropivacaine administered for labour epidural analgesia was compared in 78 women at <5 cm cervical dilatation. Women were randomly allocated to one of three groups: plain ropivacaine, ropivacaine with sufentanil 5 microg and ropivacaine with clonidine 75 microg. RESULTS The MLAC of plain ropivacaine was 0.099% wt/vol (95%CI: 0.090 to 0.109) and was reduced to 0.036% wt/vol (95% CI: 0.024 to 0.049) when combined with sufentanil 5 microg and to 0.036% wt/vol (95% CI: 0.027 to 0.046) with clonidine 75 microg (P < 0.001). The wt/wt local anesthetic sparing potency ratio of sufentanil to clonidine was 15.1 (95% CI: 10.3 to 23.4). CONCLUSIONS Sufentanil 5 microg and clonidine 75 microg produce similar reductions in the MLAC of ropivacaine. This finding will make feasible the assessment of the side effects of these adjuvants administered at equipotent doses in further studies.

Comparison between two intraoperative intravenous loading doses of paracetamol on pain after minor hand surgery: two grams versus one gram.

Summary Background: Paracetamol (acetaminophen) is widely used for postoperative analgesia at a recommended dose of 1 g every six hours in adult patients. Increasing the loading dose to 2 g was suggested to improve immediate postoperative analgesia without increased toxicity in healthy adult patients. We tested the hypothesis that a loading dose of 2 g of intravenous paracetamol results in better postoperative analgesia after surgery as compared with a dose of 1 g. Methods: Sixty adult patients scheduled for minor hand surgery under intravenous regional anaesthesia were randomized into two groups. The first group received 1 g of intravenous paracetamol before surgery while the second group received 2 g. Verbal numeric pain score, analgesic consumption, first night sleep quality, and patient’s satisfaction were recorded during the first 24 hours. Results: Verbal numeric pain scores during the first 24 hours after surgery were significantly lower in the 2 g paracetamol group as compared to the 1 g paracetamol group. No differences were found between the two groups with regard to rescue analgesic consumption, sleep quality and patient’s satisfaction. Conclusions: An intraoperative loading dose of 2 g paracetamol improves postoperative analgesia after minor hand surgery as compared to 1 g paracetamol.

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.

Functional imaging and impaired consciousness

Categorizing disorders of consciousness patients into the correct diagnostic syndrome is essential in determining prognosis and thus for accurate neurological management. Unfortunately, these patients are hardly distinguishable by means of behavioral testing alone, because they can be totally or partially aware, but unable to clearly produce appropriate motor outputs other than reflexive movements, as fluctuations of alertness. Sensory-motor impairments, use of drugs and severe general clinical conditions can strongly limit or mask the repertoire of their motor responses. All these reasons explain the high percentage of misdiagnosis, although several standardized neurobehavioral rating scales have been developed. Neuroimaging strategies cannot replace clinical evaluation, nevertheless they can describe objectively how deviant from normal patients’ cerebral activity is under various conditions of stimulation, at rest and during an active participation in simple tasks.

Positron Emission Tomography: Basic Principles, New Applications, and Studies Under Anesthesia.

Besides electroencephalography (EEG), positron emission tomography (PET) is one of the oldest tools for the exploration of the functioning brain. PET primarily focuses on neuronal activity and metabolism in the brain. It also has potential applications in studying the neurotransmitter function in the central nervous system. PET studies have laid the foundation for understanding the fundamental properties related to motor, sensory, and some cognitive functions in physiological and pathologic states. Brain function studies with PET, EEG, magnetic resonance imaging (MRI), and other neurotechnology tools have started shedding light on hitherto unknown aspects of brain function.