Neural plasticity lessons from disorders of consciousness

in Frontiers in Psychology [=FPSYG] (2011), 1

Communication and intentional behavior are supported by the brain?s integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe ... [more ▼]

Communication and intentional behavior are supported by the brain?s integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe brain injury, in many cases patients are not capable of conscious interactive behavior and are said to suffer from disorders of consciousness (e.g., coma, vegetative state /unresponsive wakefulness syndrome, minimally conscious states). This lesion paradigm has offered not only clinical insights, as how to improve diagnosis, prognosis and treatment, but also put forward scientific opportunities to study the brain?s plastic abilities. We here review interventional and observational studies performed in severely brain-injured patients with regards to recovery of consciousness. The study of the recovered conscious brain (spontaneous and/or after surgical or pharmacologic interventions), suggests a link between some specific brain areas and the capacity of the brain to sustain conscious experience, challenging at the same time the notion of fixed temporal boundaries in rehabilitative processes. Altered functional connectivity, cerebral structural reorganization as well as behavioral amelioration after invasive treatments will be discussed as the main indices for plasticity in these challenging patients. The study of patients with chronic disorders of consciousness may, thus, provide further insights not only at a clinical level (i.e., medical management and rehabilitation) but also from a scientific-theoretical perspective (i.e., the brain?s plastic abilities and the pursuit of the neural correlate of consciousness). [less ▲]

Attitudes towards end-of-life issues in disorders of consciousness : a European survey

in Journal of Neurology (2011)

Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent ... [more ▼]

Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent definition of minimally conscious state (MCS), and possibly research advances (e.g., functional neuroimaging), may have lead to uncertainty regarding potential residual perception and may have influenced opinions of healthcare professionals. The aim of the study was to update the end-of-life attitudes towards VS and to determine the end-of-life attitudes towards MCS. A 16-item questionnaire related to consciousness, pain and end-of-life issues in chronic (i.e., >1 year) VS and MCS and locked-in syndrome was distributed among attendants of medical and scientific conferences around Europe (n = 59). During a lecture, the items were explained orally to the attendants who needed to provide written yes/no responses. Chi-square tests and logistic regression analyses identified differences and associations for age, European region, religiosity, profession, and gender. We here report data on items concerning end-of-life issues on chronic VS and MCS. Responses were collected from 2,475 participants. For chronic VS (>1 year), 66% of healthcare professionals agreed to withdraw treatment and 82% wished not to be kept alive (P < 0.001). For chronic MCS (>1 year), less attendants agreed to withdraw treatment (28%, P < 0.001) and wished not to be kept alive (67%, P < 0.001). MCS was considered worse than VS for the patients in 54% and for their families in 42% of the sample. Respondents’ opinions were associated with geographic region and religiosity. Our data show that end-of-life opinions differ for VS as compared to MCS. The introduction of the diagnostic criteria for MCS has not substantially changed the opinions on end-of-life issues on permanent VS. Additionally, the existing legal ambiguity around MCS may have influenced the audience to draw a line between expressing preferences for self versus others, by implicitly recognizing that the latter could be a step on the slippery slope to legalize euthanasia. Given the observed individual variability, we stress the importance of advance directives and identification of proxies when discussing end-of-life issues in patients with disorders of consciousness. [less ▲]

Disorders of consciousness: coma, vegetative and minimally conscious states

in D. Cvetkovic & I. Cosic (Ed.) States of Consciousness: Experimental Insights into Meditation, Waking, Sleep and Dreams (2011)

Identifying the default-mode component in spatial IC analyses of patients with disorders of consciousness.

in Human Brain Mapping (2011)

Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default-mode network (DMN) in the absence of any task, by resting-state connectivity analyses in healthy volunteers ... [more ▼]

Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default-mode network (DMN) in the absence of any task, by resting-state connectivity analyses in healthy volunteers. We here aimed to identify the DMN in the challenging patient population of disorders of consciousness encountered following coma. Experimental design: A spatial independent component analysis-based methodology permitted DMN assessment, decomposing connectivity in all its different sources either neuronal or artifactual. Three different selection criteria were introduced assessing anticorrelation-corrected connectivity with or without an automatic masking procedure and calculating connectivity scores encompassing both spatial and temporal properties. These three methods were validated on 10 healthy controls and applied to an independent group of 8 healthy controls and 11 severely brain-damaged patients [locked-in syndrome (n = 2), minimally conscious (n = 1), and vegetative state (n = 8)]. Principal observations: All vegetative patients showed fewer connections in the default-mode areas, when compared with controls, contrary to locked-in patients who showed near-normal connectivity. In the minimally conscious-state patient, only the two selection criteria considering both spatial and temporal properties were able to identify an intact right lateralized BOLD connectivity pattern, and metabolic PET data suggested its neuronal origin. Conclusions: When assessing resting-state connectivity in patients with disorders of consciousness, it is important to use a methodology excluding non-neuronal contributions caused by head motion, respiration, and heart rate artifacts encountered in all studied patients. Hum Brain Mapp, 2011. (c) 2011 Wiley-Liss, Inc. [less ▲]

Near-Death Experiences : Real or imagined memories?

Poster (2010, September)

Resting-state auditory network in tinnitus: a fMRI study

Poster (2010, June)

Brain-computer interface in disorders of consciousness: answering simple questions with a P3 speller

Poster (2010, June)

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients ... [more ▼]

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients, recovery of consciousness may precede motor recovery. Brain-computer interfaces (BCI) might permit these patients to show non-motor dependent signs of awareness and in a next step might enable communication. This study aimed at testing to what extent an EEG-based BCI could help detecting signs of awareness and communication in disorders of consciousness. We employed a P300 based BCI where healthy volunteers and patients with locked-in syndrome and in a minimally conscious state were asked to answer yes or no to simple questions by paying attention to one out of four auditorily presented stimuli (‘yes’, ‘no’, ‘stop’, ‘go’). Methods: We studied 13 patients with a minimally conscious state (MCS, 5 TBI – 8 anoxic, mean time post injury 70±109 months; mean age 42 ± 21) and 2 in pseudo-coma or locked in syndrome (LIS; brainstem stroke, time post injury 26 and 46 months; aged 63 and 29)) and 16 healthy controls (aged 45±19). Patients were evaluated using the Coma Recovery Scale Revised (CRS-R). An auditory P300 four choice speller paradigm (Furdea et al., 2009) based on the BCI2000 system (Schalk et al., 2004) was used. 16-Channel EEG was recorded using a g.tec USBAmp amplifier. A trial constituted of 15 presentation of four sounds the order of presentation being pseudo-randomized (sound duration: ~400ms; inter-stimulus interval: ~600ms). After a training session of 4 trials, patients and healthy subjects were required to answer 10 or 12 questions, respectively. Questions were of the following kind: “Is your name Quentin?”, “Is your mother’s name Dorothée?”. A stepwise linear discriminant analysis based on the training session was used to classify the data and to provide online feedback. Offline, all training and testing sequences were pooled. Sequences with artifacts were discarded and a leave-one-out approach was used to classify the data. Results: Healthy subjects presented a mean correct response rate of 73% online and 93% offline. Note that online classification failed for one control subject due to a presumed change in cognitive strategy between training and testing sessions. LIS patients showed a correct response rate of 30 and 60% (online) and 36 and 79% (offline). Three MCS patients had a correct response rate of ≥50% offline (10, 18, 0% online and 50, 53, 57% offline). Two of these three patients did not show any command following at the bedside. The 10 remaining MCS cases showed online and offline correct answers <50% (mean 33±9% online and 25±13% offline). Conclusion: Our auditory P300-based BCI permitted functional interactive communication in 15/16 controls (online) and in all offline. Our data obtained in patients with locked-in syndrome and disorders of consciousness demonstrate the potential clinical usefulness of the technique following coma but also show lower accuracy in patients as compared to healthy volunteers. This might be due to fluctuating attentional levels and exhaustibility in the MCS and to the suboptimal EEG recording quality due to movement, ocular and respiration artifacts in these challenging patients. Further algorithmic developments should include automatic artifact detection and single trial classification. Despite the need for further improvement in BCI devices adapted to post-coma patients, our results already indicate that MCS patients without any clinical sign of command-following can employ a yes-no speller offering the hope of functional interactive communication and a possibility for decision making and autonomy. Bibliography Furdea A, Halder S, Krusienski DJ, Bross D, Nijboer F, Birbaumer N, Kübler A, 2009, An auditory oddball (P300) spelling system for brain-computer interfaces, Psychophysiology. May; 46(3):617-25. Schalk G., McFarland D.J., Hinterberger T., Birbaumer N., and Wolpaw J.R. 2004, BCI2000: A General-Purpose Brain-Computer Interface (BCI) System, IEEE Trans Biomed Eng, 51(6). Schnakers C, Vanhaudenhuyse A, Giacino J, Ventura; Boly M, Majerus S, Moonen G, Laureys S, 2009, Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment, BMC Neurology, 9 (35). [less ▲]

Near-death experiences: real or imagined?

Conference (2010, June)

Disorders of consciousness: Moving from passive to resting state and active paradigms

in Cognitive Neuroscience (2010), 1(1), 193203

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e ... [more ▼]

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e., minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state. The increasing use of fMRI and EEG tools permits the clinical characterization of these patients to be improved. We first discuss “resting metabolism” and “passive activation” paradigms, used in neuroimaging and evoked potential studies, which merely identify neural activation reflecting “automatic” processing—that is, occurring without the patient’s willful intervention. Secondly, we present an alternative approach consisting of instructing subjects to imagine well-defined sensorymotor or cognitive-mental actions. This strategy reflects volitional neural activation and, hence, witnesses awareness. Finally, we present results on blood-oxgen-level-dependent “default mode network”/resting state studies that might be a promising tool in the diagnosis of these challenging patients. [less ▲]

Visual fixation in the vegetative state: an observational case series PET study.

in BMC Neurology (2010), 10

BACKGROUND: Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether ... [more ▼]

BACKGROUND: Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents "automatic" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing. METHODS: We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria. RESULTS: Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome). CONCLUSIONS: Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function. [less ▲]