Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness.

OBJECTIVE: This study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. METHODS: We enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale-Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. RESULTS: Power spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. CONCLUSIONS: Auditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SIGNIFICANCE: Our findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

Assessing the depth of language processing in patients with disorders of consciousness.

Assessing residual consciousness and cognitive abilities in unresponsive patients is a major clinical concern and a challenge for cognitive neuroscience. Although neuroimaging studies have demonstrated a potential for informing diagnosis and prognosis in unresponsive patients, these methods involve sophisticated brain imaging technologies, which limit their clinical application. In this study, we adopted a new language paradigm that elicited rhythmic brain responses tracking the single-word, phrase and sentence rhythms in speech, to examine whether bedside electroencephalography (EEG) recordings can help inform diagnosis and prognosis. EEG-derived neural signals, including both speech-tracking responses and temporal dynamics of global brain states, were associated with behavioral diagnosis of consciousness. Crucially, multiple EEG measures in the language paradigm were robust to predict future outcomes in individual patients. Thus, EEG-based language assessment provides a new and reliable approach to objectively characterize and predict states of consciousness and to longitudinally track individual patients' language processing abilities at the bedside.

Low- and medium-rate auditory steady-state responses in patients with prolonged disorders of consciousness correlate with Coma Recovery Scale - Revised score.

Diagnosis of consciousness in patients with prolonged disorders of consciousness (PDOC) remains challenging since their responsiveness is often very impaired, while their assessment depends on observable behavior. The aim of this proof-of-concept study was to evaluate whether low- and medium-rate amplitude-modulated (AM) auditory steady-state responses (ASSRs) can be sensitive to the state of PDOC patients and may thus serve as a diagnostic tool which does not explicitly depend on a patient's cooperation. EEG was recorded from nine unresponsive wakefulness syndrome/vegetative state (UWS/VS) and eight minimally conscious state (MCS)/emergence from MCS patients during stimulation with two-minute trains of simple tones, amplitude modulated (AM) by 4 Hz, 6 Hz, 8 Hz, 12 Hz, 20 Hz, 40 Hz. The obtained ASSRs were then related to the Coma Recovery Scale - Revised (CRS-R) diagnosis and its total score. We observed significant correlations between mean inter-trial phase coherence (PC) (averaged across all stimulation frequencies) and total CRS-R score, as well as between 40 Hz relative power (RP) and total CRS-R score. Moreover, both parameters significantly differed between the patient groups. Our preliminary results suggest that a passive auditory stimulation protocol consisting of low- and medium-rate ASSRs might be used as an objective estimate of the level of neural dysfunction in PDOC patients. Consequently, the integrity of the auditory system appears to be an important predictor of the actual state of consciousness in PDOC patients.

Event-related potentials in the odd-ball paradigm and behavioral scales for the assessment of children and adolescents with disorders of consciousness: A proof of concept study.

OBJECTIVE: Quantification of signatures of conscious processing in children with disorders of consciousness (DoC) using odd-ball paradigms in multiple modalities. METHOD: We review the diagnostic approaches available in the field, from clinical scales to neuroimaging methods, and concentrate upon measures derived from electroencephalographic event related potentials. RESULTS: Evoked potentials were recorded in five procedures, encompassing visual, auditory and tactile modalities, from ten pediatric DoC patients-six in a minimally conscious state (MCS), three in unresponsive wakefulness syndrome (UWS) and one who emerged from MCS (eMCS)-and the control group of 10 healthy children. In almost all the eMCS and MCS patients, higher amplitude of P300 was observed and the effect was statistically significant in at least one out of the five performed procedures. Additionally, signs of conscious information processing were detected in one UWS patient. CONCLUSION: The presented results provide a proof of concept for the possibility of applying ERP-derived electrophysiological measures as an aid in the assessment of children and adolescents in DoC.

Information processing in patients in vegetative and minimally conscious states.

OBJECTIVE: Evaluation of a short two-tone oddball paradigm to discriminate between the vegetative state (VS) and minimal consciousness state (MCS) in a sample of patients with severe disorders of consciousness (DOC). METHOD: EEG was recorded from 45 DOC patients and 14 healthy participants while listening to an auditory oddball paradigm presented in a passive - just listen - and an active - count the odd tones - condition. In patients, the experiment was repeated after a minimum of one week. RESULTS: Prevalence of the P300 was higher in healthy participants (71%) than in patients, but did not discriminate between VS (T1: ∼10%; T2: ∼11%) and MCS (T1: ∼13%; T2: 25%) patients. CONCLUSION: Results cast doubt on whether this simple auditory stimulation paradigm, which requires cognitive action from the listener, is sensitive enough to discriminate between patients with DOC. SIGNIFICANCE: The sensitivity of the P300 ERP obtained in a short two-tone oddball paradigm presented in a passive and an active condition appears to be too low for routine application in a clinical setting aiming at distinguishing between VS and MCS patients.

EEG entropy measures indicate decrease of cortical information processing in Disorders of Consciousness.

OBJECTIVE: Clinical assessments that rely on behavioral responses to differentiate Disorders of Consciousness are at times inapt because of some patients' motor disabilities. To objectify patients' conditions of reduced consciousness the present study evaluated the use of electroencephalography to measure residual brain activity. METHODS: We analyzed entropy values of 18 scalp EEG channels of 15 severely brain-damaged patients with clinically diagnosed Minimally-Conscious-State (MCS) or Unresponsive-Wakefulness-Syndrome (UWS) and compared the results to a sample of 24 control subjects. Permutation entropy (PeEn) and symbolic transfer entropy (STEn), reflecting information processes in the EEG, were calculated for all subjects. Participants were tested on a modified active own-name paradigm to identify correlates of active instruction following. RESULTS: PeEn showed reduced local information content in the EEG in patients, that was most pronounced in UWS. STEn analysis revealed altered directed information flow in the EEG of patients, indicating impaired feed-backward connectivity. Responses to auditory stimulation yielded differences in entropy measures, indicating reduced information processing in MCS and UWS. CONCLUSIONS: Local EEG information content and information flow are affected in Disorders of Consciousness. This suggests local cortical information capacity and feedback information transfer as neural correlates of consciousness. SIGNIFICANCE: The utilized EEG entropy analyses were able to relate to patient groups with different Disorders of Consciousness.

Neurophysiological assessment for evaluating residual cognition in vegetative and minimally conscious state patients: a pilot study.

The aim of this study was to assess residual cognitive function and perform outcome evaluation in vegetative state (VS) and minimally conscious state (MCS) patients, using Neurowave, a system able to monitor event-related potentials (ERPs) induced by neurosensory stimulation. Eleven VS and five MCS patients underwent neurological examination and clinical evaluation performed using validated clinical and behavioral scales; they also underwent neurosensory stimulation, which consisted of administration of target images (rare stimuli), relevant to the patient's personal history and having emotional significance, alternated with nontarget images ("standard" stimuli), which had no emotional significance. All simultaneous ERP responses at baseline (T0) and at three months from T0 (T1) were recorded. At T0 we found significant differences between the VS and MCS patients for the N200 (p=0.02) and P300 (p=0.04) waves. The neurophysiological analysis at T1 showed a significant difference only for P300 (p=0.02), probably due to the improvements observed in the VS subjects for the N100 (p=0.009) and N200 (p=0.02) sensory components. Neurophysiological assessment for evaluating residual cognition in vegetative and minimally conscious state patients: a pilot study Our findings seem to show the value of ERP monitoring in VS and MCS patients as a means of investigating residual cognitive function. This approach could guide early therapeutic and rehabilitation interventions, and contribute to identifying better diagnostic and prognostic markers for use in unresponsive or low-responsive patients.

[Recovery of consciousness as manifestation of neuroplasticity].

Prolonged impairment of consciousness is one of the most fearsome syndromes during diseases and traumas of nervous system. Traumatic brain injury (TBI) is the cause of coma with outcome in vegetative state in approximately half of cases which allows considering this etiopathogenetic form of consciousness impairment as one of the models for studying its morphofunctional nature because the pathogenesis of TBI is mostly understood. Particularly, it has been showed that in the basis of clinical picture of TBI lie, on the one hand, morphological (diffuse axonal injury of subcortical white matter, necrotic changes in cortex, thalamus) and functional (diaschisis) disturbances and on the other--processes of sanogenesis occurring within the borders of neuroplasticity. The aim of our research was to investigate clinical and neurophysiological markers of consciousness recovery in patients with vegetative state (VS) after severe TBI by comparison of clinical changes dynamics and brain bioelectrical activity. In all patients we have evaluated neurological status, Glasgow coma scale, performed registration and spectral-coherent analysis of electroencephalography and also registration and analysis of somatosensory potentials, studied motor thresholds, amplitude-time characteristics of evoked motor potentials during transcranial magnetic stimulation, repeatedly conducted MRI or CT. The electroencephalography in most of the patients revealed theta- and delta-rhythm sometimes with signs of paroxysmal activity and interhemispheric asymmetry or low-amplitude EEG. It is estimated that reliable positive changes in amplitude-time characteristics of multimodal evoked potentials, reliable decrease of motor thresholds mostly in left hemisphere and increase of motor evoked potentials amplitude are in 5-7 preceded by clinical improvement in patients with TBI.

Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation?

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.

[Dog-based multi-sensorial therapy of a patient with a "persistent vegetative state"--a case report]. / Hundgestützte multisensorische Therapie bei einer Patientin mit "persistierendem vegetativen Zustand"--ein Fallbericht.

AIM: There is evidence that animal-assisted therapy can have beneficial effects in patients with cognitive disorders. In the present case study, the influence of animal-assisted therapy was to be investigated in a patient with most severe cerebral lesions. METHODS: A 27 year old patient with a persistent vegetative state since 5 years after severe traumatic brain injury received long term treatment by 54 sessions of animal-assisted therapy. RESULTS: During the course of the therapeutic interventions, the patient showed more and more signs of vegetative, emotional and motor reactions. The latter were increasingly target-bound and at last allowed a simple type of non-verbal communication. CONCLUSION: The present case indicates that animal-assisted therapy can be a reasonable option to treat patients with most severe cerebral lesions. Furthermore, the results illustrate that the usual diagnostic classification such as "persistent vegetative state" based on a neurological investigation alone may be questionable. Possible reasons for the impact of animal-assisted therapy are complex and comprise e.g. multiple sensory stimuli.

Conscious awareness in patients in vegetative states: myth or reality?

Do vegetative state (VS) and minimally conscious state (MCS) patients experience emotions and have conscious awareness of themselves and their surroundings? Can neuroimaging clarify these questions? Neuroimaging responses to stimuli are classified into four levels: level 0 indicates no response; level 1 indicates responses limited to the primary sensory cortices; level 2 indicates activation of primary sensory cortices and higher-order associative areas; level 3 indicates activation of cortical regions to either mental imagery tasks or high-level language stimuli requiring distinction of ambiguous from unambiguous words. Level 0 or level 1 was noted in 125 of 193 VS patients (65 %) and 46 of 121 MCS patients (38 %), suggesting no evidence of conscious awareness. Level 2 or level 3 was observed in 68 of 193 VS patients (35 %) and 75 of 121 MCS patients (62 %), indicating some cognitive processing. These data may denote the presence of conscious awareness or may simply identify neuronal processing without phenomenological awareness. The pro and cons of these conflicting interpretations are discussed.

Global functional connectivity reveals highly significant differences between the vegetative and the minimally conscious state.

A major challenge in the diagnosis of disorders of consciousness is the differential diagnosis between the vegetative state (VS) and the minimally conscious state (MCS). Clinically, VS is defined by complete unawareness, whereas MCS is defined by the presence of inconsistent but clearly discernible behavioural signs of consciousness. In healthy individuals, pain cries have been reported to elicit functional activation within the pain matrix of the brain, which may be interpreted as empathic reaction. In this study, pain cries were presented to six VS patients, six MCS patients, and 17 age-matched healthy controls. Conventional task-related functional magnetic resonance imaging (fMRI) showed no significant differences in functional activation between the VS and MCS groups. In contrast to this negative finding, the application of a novel data-driven technique for the analysis of the brain's global functional connectivity yielded a positive result. The weighted global connectivity (WGC) was significantly greater in the MCS group compared to the VS group (p < 0.05, family-wise error corrected). Using areas of significant WGC differences as 'seed regions' in a secondary connectivity analysis revealed extended functional networks in both MCS and healthy groups, whereas no such long-range functional connections were observed in the VS group. These results demonstrate the potential of functional connectivity MRI (fcMRI) as a clinical tool for differential diagnosis in disorders of consciousness.

Focal increase in cerebral blood flow after treatment with near-infrared light to the forehead in a patient in a persistent vegetative state.

OBJECTIVE: This study aimed to quantify the cerebral blood flow (CBF) after bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to the forehead in a patient in a persistent vegetative state following severe head injury. BACKGROUND DATA: Positive behavioral improvement has been observed following transcranial near-infrared light therapy in humans with chronic traumatic brain injury and acute stroke. METHODS: Single-photon emission computed tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed following a series of LED treatments. RESULTS: IMP-SPECT showed unilateral, left anterior frontal lobe focal increase of 20%, compared to the pre-treatment value for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days from an array of 23×850 nm LEDs, 13 mW each, held 5 mm from the skin, 30 min per session, the power density 11.4 mW/cm(2); the energy density 20.5 J/cm(2) at the skin. The patient showed some improvement in his neurological condition by moving his left arm/hand to reach the tracheostomy tube, post-LED therapy. CONCLUSIONS: Transcranial LED might increase rCBF with some improvement of neurological condition in severely head-injured patients. Further study is warranted.

Microswitch technology and contingent stimulation to promote adaptive engagement in persons with minimally conscious state: a case evaluation.

This study assessed whether a post-coma woman functioning at the lower end of the minimally conscious state would (a) develop adaptive responding through the use of microswitch technology and contingent stimulation, (b) consolidate and maintain her responding over time, and (c) show evidence of response-consequences awareness (learning and discrimination). The study involved an ABABB1CB1 sequence in which the A represented baseline phases, the B and B1 intervention phases, and the C a control phase with continuous stimulation. Results indicated that the woman developed adaptive responding and consolidated it over the intervention phases of the study. The woman also showed evidence of being aware of response-consequences links. Potential implications and limitations of these findings are discussed.

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.

Source imaging of QEEG as a method to detect awareness in a person in vegetative state.

BACKGROUND: Assessment of awareness in patients with severe brain injury remains subjective, although patients with even limited awareness (e.g. minimal conscious state, MCS) have different prognoses and treatment than those in vegetative state (VS). Recently, task appropriate differential regional activation in VS has been reported using fMRI during mental imagery. PRIMARY OBJECTIVE: Demonstration of conscious awareness in reproducible differential EEG source localization images in a VS patient reflecting requested mental imagery was performed. METHODS: A VS patient (with re-test) and a normal control were requested to imagine singing and to mentally perform serial subtraction, while EEG was recorded. QEEG source localization was performed to identify regions of brain activation in response to tasks. RESULTS: Replicable distinctive activation of brain areas appropriate for each task was seen in the VS patient and control. Frequency spectra shifted to beta, with significant source activation in regions including the bilateral anterior cingulate, insula, left caudate and dorsolateral pre-frontal cortex to singing and the putamen, insula, left pre-frontal cortex and right temporal gyrus to subtraction by 7's. CONCLUSIONS: Results from this single case suggests the potential utility of QEEG source localization images to detect awareness in patients clinically diagnosed as being in VS. This indicates the possibility that EEG may serve as an important adjunct to the assessment of awareness in patients with disorders of consciousness in the clinical setting.

Application of nonlinear dynamics analysis in assessing unconsciousness: a preliminary study.

OBJECTIVES: To quantify the degree of unconsciousness with EEG nonlinear analysis and investigate the change of EEG nonlinear properties under different conditions. METHODS: Twenty-one subjects in persistent vegetative state (PVS), 16 in minimally conscious state (MCS) and 30 normal conscious subjects (control group) with brain trauma or stroke were involved in the study. EEG was recorded under three conditions: eyes closed, auditory stimuli and painful stimuli. EEG nonlinear indices such as Lempel-Ziv complexity (LZC), approximate entropy (ApEn) and cross-approximate entropy (cross-ApEn) were calculated for all the subjects. RESULTS: The PVS subjects had the lowest nonlinear indices followed by the MCS subjects and the control group had the highest. The PVS and MCS group had poorer response to auditory and painful stimuli than the control group. Under painful stimuli, nonlinear indices of subjects who recovered (REC) increased more significantly than non-REC subjects. CONCLUSIONS: With EEG nonlinear analysis, the degree of suppression for PVS and MCS could be quantified. The changes of brain function for unconscious subjects could be captured by EEG nonlinear analysis. SIGNIFICANCE: EEG nonlinear analysis could characterise the changes of brain function for unconscious state and might have some value in predicting prognosis of unconscious subjects.

Event-related brain potential modulation in patients with severe brain damage.

OBJECTIVE: The limited evidence and inconsistency of purposeful behaviors in patients in a minimally conscious state (MCS) asks for objective electrophysiological marker of the level of consciousness. Here, a comparison between event-related potentials (ERPs) was investigated using different level of stimulus complexity. METHODS: The patients in vegetative state were 11 and the MCS patients were 6 [corrected]. Three oddball paradigms with different level of complexity were applied: sine tones, the subject's own name versus sine tones and other first names. Latencies and amplitudes of N1 and P3 waves were compared. RESULTS: Cortical responses were found in all MCS patients, and in 6 of 11 patients in VS. Healthy controls and MCS patients showed a progressive increase of P3 latency in relation to the level of stimulus complexity. No modulation of P3 latency was observed in the vegetative patients. CONCLUSIONS: These results suggest that the modulation of P3 latency related to stimulus complexity may represent an objective index of higher-order processing integration that predicts the recovery of consciousness from VS to MCS when clinical manifestations are inconsistent. SIGNIFICANCE: Modulation of P3 latency related to stimulus complexity could provide valuable information about the cognitive capabilities of unresponsive patients.

Willful modulation of brain activity in disorders of consciousness.

BACKGROUND: The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient's capacity to show behavioral signs of awareness is diminished. METHODS: At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient's ability to generate willful, neuroanatomically specific, blood-oxygenation-level-dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions. RESULTS: Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside. CONCLUSIONS: These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive.