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 ▲]

Multimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy".

in Progress in Brain Research (2011), 193

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information ... [more ▼]

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information on the structural location and extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI-MRI) assessing structural connectivity) but also their functional impact (e.g., metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting state" conditions). We here illustrate the role of multimodal imaging in severe brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS; i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally preserved right hemisphere, while DTI showed underlying differences in structural connectivity highlighting the complementarities of these neuroimaging methods in the study of disorders of consciousness. [less ▲]

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 ▲]

Brain connectivity in pathological and pharmacological coma

in Frontiers in Systems Neuroscience [=FNSYS] (2010), 4

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the ... [more ▼]

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low-level cortical activation in response to external stimulation in patients in a “vegetative state” or unresponsive wakefulness syndrome. While activation of these “primary” sensory cortices does not necessarily reflect conscious awareness, activation in higher-order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread frontoparietal “global neuronal workspace” in DOC patients including the midline default mode network (“intrinsic” system) and the lateral frontoparietal cortices or “extrinsic system.” Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma, and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory, or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between “intrinsic” and “extrinsic” brain networks. [less ▲]

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 ▲]

Resting-state auditory network in tinnitus: a fMRI study

Conference (2010, March)

Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.

in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]

Functional Neuroimaging Approaches to the Changing Borders of Consciousness

in Journal of Psychophysiology (2010), 24(2), 68-75

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could ... [more ▼]

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could help disentangle complex cases and offer new prognostic criteria. These methods can be divided into to three categories: First, new anatomical MRI neuroimaging methods, like diffusion tensor imaging (DTI) or spectroscopy, and passive functional imaging methods (looking at the brain’s activation induced by external stimuli), could provide new diagnostic and prognostic markers. Second, neuroimaging methods based on active collaboration from the patient could help to detect clinically unnoticed signs of consciousness. Third, developments in brain-computer interfaces based on EEG, functional MRI, or EMG offer communication possibilities in brain-damaged patients who can neither verbally nor nonverbally express their thoughts or wishes. These new approaches raise important issues not only from a clinical and ethical perspective (i.e., patients’ diagnosis, prognosis and management) but also from a neuroscientific standpoint, as they enrich our current understanding of the emergence and function of the conscious human mind. [less ▲]