Correction to: Actigraphy assessments of circadian sleep-wake cycles in the Vegetative and Minimally Conscious States.

The original article [1] contains an error affecting the actigraphy time-stamps throughout the article, particularly in Table 1.

Single-trial decoding of auditory novelty responses facilitates the detection of residual consciousness.

Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract subject-specific EEG patterns and predict single-trial local or global novelty responses. We first validate our method with 38 high-density EEG, MEG and intracranial EEG recordings. We empirically demonstrate that our approach circumvents the issues associated with multiple comparisons and individual variability while improving the statistics. Moreover, we confirm in control subjects that local responses are robust to distraction whereas global responses depend on attention. We then investigate 104 vegetative state (VS), minimally conscious state (MCS) and conscious state (CS) patients recorded with high-density EEG. For the local response, the proportion of significant decoding scores (M=60%) does not vary with the state of consciousness. By contrast, for the global response, only 14% of the VS patients' EEG recordings presented a significant effect, compared to 31% in MCS patients' and 52% in CS patients'. In conclusion, single-trial multivariate decoding of novelty responses provides valuable information in non-communicating patients and paves the way towards real-time monitoring of the state of consciousness.

Cognitive processing during the transition to sleep.

Dramatic physiological and behavioural changes occur during the transition from wakefulness to sleep. The process is regarded as a grey area of consciousness between attentive wakefulness and slow wave sleep. Although there is evidence of neurophysiological integration decay as signalled by sleep EEG elements, changes in power spectra and coherence, thalamocortical connectivity in fMRI, and single neuron changes in firing patterns, little is known about the cognitive and behavioural dynamics of these transitions. Hereby we revise the body and brain physiology, behaviour and phenomenology of these changes of consciousness and propose an experimental framework to integrate the two aspects of consciousness that interact in the transition, wakefulness and awareness.

Relationship between etiology and covert cognition in the minimally conscious state.

OBJECTIVES: Functional neuroimaging has shown that the absence of externally observable signs of consciousness and cognition in severely brain-injured patients does not necessarily indicate the true absence of such abilities. However, relative to traumatic brain injury, nontraumatic injury is known to be associated with a reduced likelihood of regaining overtly measurable levels of consciousness. We investigated the relationships between etiology and both overt and covert cognitive abilities in a group of patients in the minimally conscious state (MCS). METHODS: Twenty-three MCS patients (15 traumatic and 8 nontraumatic) completed a motor imagery EEG task in which they were required to imagine movements of their right-hand and toes to command. When successfully performed, these imagined movements appear as distinct sensorimotor modulations, which can be used to determine the presence of reliable command-following. The utility of this task has been demonstrated previously in a group of vegetative state patients. RESULTS: Consistent and robust responses to command were observed in the EEG of 22% of the MCS patients (5 of 23). Etiology had a significant impact on the ability to successfully complete this task, with 33% of traumatic patients (5 of 15) returning positive EEG outcomes compared with none of the nontraumatic patients (0 of 8). CONCLUSIONS: The overt behavioral signs of awareness (measured with the Coma Recovery Scale-Revised) exhibited by nontraumatic MCS patients appear to be an accurate reflection of their covert cognitive abilities. In contrast, one-third of a group of traumatically injured patients in the MCS possess a range of high-level cognitive faculties that are not evident from their overt behavior.

Probing consciousness with event-related potentials in the vegetative state.

OBJECTIVE: Probing consciousness in noncommunicating patients is a major medical and neuroscientific challenge. While standardized and expert behavioral assessment of patients constitutes a mandatory step, this clinical evaluation stage is often difficult and doubtful, and calls for complementary measures which may overcome its inherent limitations. Several functional brain imaging methods are currently being developed within this perspective, including fMRI and cognitive event-related potentials (ERPs). We recently designed an original rule extraction ERP test that is positive only in subjects who are conscious of the long-term regularity of auditory stimuli. METHODS: In the present work, we report the results of this test in a population of 22 patients who met clinical criteria for vegetative state. RESULTS: We identified 2 patients showing this neural signature of consciousness. Interestingly, these 2 patients showed unequivocal clinical signs of consciousness within the 3 to 4 days following ERP recording. CONCLUSIONS: Taken together, these results strengthen the relevance of bedside neurophysiological tools to improve diagnosis of consciousness in noncommunicating patients.

A multimodal approach to the assessment of patients with disorders of consciousness.

Unlike other neurological conditions, the heterogeneous pathology linked to disorders of consciousness currently excludes a distinction between the vegetative and minimally conscious states based upon pathological presentation. The clinical assessment is therefore made on the basis of the patient's clinical history and exhibited behaviour. This creates a particular challenge for the clinician who has to decide whether a certain behaviour, which might be inconsistent or incomplete, reflects a conscious or an unconscious process. In an alarmingly high number of cases, identified during clinical audit, this decision process has been shown to be particularly fallible. The behavioural assessment is not only highly subjective, but also dependent upon the ability of the patient to move or speak; it is the only way someone can demonstrate they are aware. To address this problem we propose a multimodal approach, which integrates objective tools, such as electrophysiology and functional brain imaging, with traditional behavioural scales. Together this approach informs the clinical decision process and resolves many of the dilemmas faced by clinicians interpreting solely behavioural indices. This approach not only provides objective information regarding the integrity of residual cognitive function, but also removes the dependency on the patient to move or speak by using specially designed paradigms that do not require a motor output in order to reveal awareness of self or environment. To demonstrate this approach we describe the case of BW, who sustained a traumatic brain injury seven months prior to investigation. BW was admitted to a five-day assessment programme, which implemented our multimodal approach. On behavioural assessment BW demonstrated evidence of orientation and visual pursuit. However, he showed no response to written or verbal command, despite holding command cards and scanning text. Electrophysiology confirmed that he retained a preserved neural axis supporting vision and hearing, and suggested some evidence that he was able to create a basic memory trace. A hierarchical fMRI auditory paradigm suggested he was able to perceive sound and speech, but revealed no evidence of speech comprehension or ability to respond to command. This was corroborated in the visual modality using a hierarchical paradigm demonstrating that he was able to perceive motion, objects and faces, but retained no evidence of being able to respond to command. We briefly review work by other teams advocating the use of brain imaging and electrophysiology and discuss the steps that are now required in order to create an international standard for the assessment of persons with impaired consciousness after brain injury.

Circadian rhythms in the vegetative state.

OBJECTIVE: To evaluate whether vegetative state patients maintain circadian rhythms. RESEARCH DESIGN: An observational study of five single cases. METHODS AND PROCEDURES: Five chronic vegetative state patients underwent clinical and neurological evaluations and 2-week continuous temperature measurements. MAIN OUTCOMES AND RESULTS: The two patients with traumatic brain injury showed well-formed circadian temperature rhythms and had more reflexive behaviours and relatively low cortical and sub-cortical atrophy, whereas the three patients from anoxic-hypoxic origin demonstrated no cycles or rhythmic behaviour. CONCLUSIONS: The presence of periods of wakefulness does not imply preserved sleep-wake cycling capacity, nor preserved circadian rhythms and it should not be taken as a distinguishing feature for the definition of the vegetative state.

Can electromyography objectively detect voluntary movement in disorders of consciousness?

Determining conscious processing in unresponsive patients relies on subjective behavioural assessment. Using data from hand electromyography, the authors studied the occurrence of subthreshold muscle activity in response to verbal command, as an objective indicator of awareness in 10 disorders of consciousness patients. One out of eight vegetative state patients and both minimally conscious patients (n = 2) demonstrated an increased electromyography signal specifically linked to command. These findings suggest electromyography could be used to assess awareness objectively in pathologies of consciousness.

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease.

BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.