RESUMO
BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).
Assuntos
Lesões Encefálicas , Transtornos da Consciência , Transtornos Dissociativos , Estado Vegetativo Persistente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Cognição/fisiologia , Transtornos da Consciência/diagnóstico por imagem , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Eletroencefalografia , Imageamento por Ressonância Magnética , Estado Vegetativo Persistente/diagnóstico por imagem , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/fisiopatologia , Estudos Prospectivos , Transtornos Dissociativos/diagnóstico por imagem , Transtornos Dissociativos/etiologia , Transtornos Dissociativos/fisiopatologiaRESUMO
OBJECTIVE: 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. METHODS: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
Assuntos
Conscientização/fisiologia , Lesões Encefálicas/patologia , Encéfalo/patologia , Coma/patologia , Transtornos da Consciência/patologia , Estado de Consciência/fisiologia , Vigília/fisiologia , Adolescente , Adulto , Idoso , Atrofia , Prosencéfalo Basal/patologia , Prosencéfalo Basal/fisiopatologia , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Encéfalo/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Mapeamento Encefálico , Tronco Encefálico/patologia , Tronco Encefálico/fisiopatologia , Estudos de Casos e Controles , Coma/etiologia , Coma/fisiopatologia , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Estudos Transversais , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/patologia , Estado Vegetativo Persistente/fisiopatologia , Índice de Gravidade de Doença , Tálamo/patologia , Tálamo/fisiopatologia , Adulto JovemRESUMO
Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.
Assuntos
Encéfalo/fisiologia , Estado de Consciência/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Rede Nervosa/fisiologia , Estado Vegetativo Persistente/fisiopatologia , Adulto , Análise por Conglomerados , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Functional neuroimaging of covert perceptual and cognitive processes can inform the diagnoses and prognoses of patients with disorders of consciousness, such as the vegetative and minimally conscious states (VS;MCS). Here we report an event-related potential (ERP) paradigm for detecting a hierarchy of auditory processes in a group of healthy individuals and patients with disorders of consciousness. Simple cortical responses to sounds were observed in all 16 patients; 7/16 (44%) patients exhibited markers of the differential processing of speech and noise; and 1 patient produced evidence of the semantic processing of speech (i.e. the N400 effect). In several patients, the level of auditory processing that was evident from ERPs was higher than the abilities that were evident from behavioural assessment, indicating a greater sensitivity of ERPs in some cases. However, there were no differences in auditory processing between VS and MCS patient groups, indicating a lack of diagnostic specificity for this paradigm. Reliably detecting semantic processing by means of the N400 effect in passively listening single-subjects is a challenge. Multiple assessment methods are needed in order to fully characterise the abilities of patients with disorders of consciousness.
Assuntos
Percepção Auditiva/fisiologia , Córtex Cerebral/fisiopatologia , Transtornos da Consciência/fisiopatologia , Potenciais Evocados Auditivos , Estimulação Acústica , Adolescente , Adulto , Idoso , Biomarcadores , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Semântica , Percepção da Fala/fisiologia , Adulto JovemRESUMO
OBJECTIVE: We employed functional MRI (fMRI) to assess whether (1) patients with disorders of consciousness (DOC) retain the ability to willfully engage in top-down processing and (2) what neurophysiologic factors distinguish patients who can demonstrate this ability from patients who cannot. METHODS: Sixteen volunteers, 8 patients in vegetative state (VS), 16 minimally conscious patients (MCS), and 4 exit from MCS (eMCS) patients were enrolled in a prospective cross-sectional fMRI study. Participants performed a target detection task in which they counted the number of times a (changing) target word was presented amidst a set of distractors. RESULTS: Three of 8 patients diagnosed as being in a VS exhibited significant activations in response to the task, thereby demonstrating a state of consciousness. Differential activations across tasks were also observed in 6 MCS patients and 1 eMCS patient. A psycho-physiologic interaction analysis revealed that the main factor distinguishing patients who responded to the task from those who did not was a greater connectivity between the anterior section of thalamus and prefrontal cortex. CONCLUSIONS: In our sample of patients, the dissociation between overt behavior observable in clinical assessments and residual cognitive faculties is prevalent among DOC patients (37%). A substantial number of patients, including some diagnosed with VS, can demonstrate willful engagement in top-down cognition. While neuroimaging data are not the same as observable behavior, this suggests that the mental status of some VS patients exceeds what can be appreciated clinically. Furthermore, thalamo-frontal circuits might be crucial to sustaining top-down functions.
Assuntos
Cognição/fisiologia , Lobo Frontal/fisiopatologia , Vias Neurais/fisiopatologia , Estado Vegetativo Persistente/fisiopatologia , Tálamo/fisiopatologia , Estimulação Acústica , Adulto , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Transtornos da Consciência/fisiopatologia , Estudos Transversais , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Recent research suggests that despite the seeming inability of patients in vegetative and minimally conscious states to generate consistent behaviour, some might possess covert awareness detectable with functional neuroimaging. These findings motivate further research into the cognitive mechanisms that might support the existence of consciousness in these states of profound neurological dysfunction. One of the key questions in this regard relates to the nature and capabilities of attention in patients, known to be related to but distinct from consciousness. Previous assays of the electroencephalographic P300 marker of attention have demonstrated its presence and potential clinical value. Here we analysed data from 21 patients and 8 healthy volunteers collected during an experimental task designed to engender exogenous or endogenous attention, indexed by the P3a and P3b components, respectively, in response to a pair of word stimuli presented amongst distractors. Remarkably, we found that the early, bottom-up P3a and the late, top-down P3b could in fact be dissociated in a patient who fitted the behavioural criteria for the vegetative state. In juxtaposition with healthy volunteers, the patient's responses suggested the presence of a relatively high level of attentional abilities despite the absence of any behavioural indications thereof. Furthermore, we found independent evidence of covert command following in the patient, as measured by functional neuroimaging during tennis imagery. Three other minimally conscious patients evidenced non-discriminatory bottom-up orienting, but no top-down engagement of selective attentional control. Our findings present a persuasive case for dissociable attentional processing in behaviourally unresponsive patients, adding to our understanding of the possible levels and applications of consequent conscious awareness.
RESUMO
It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple auditory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cognition, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition.
RESUMO
OBJECTIVE: To compare the clinical consultations provided by American and Kenyan pharmacy students in an acute care setting in a developing country. METHODS: The documented pharmacy consultation recommendations made by American and Kenyan pharmacy students during patient care rounds on an advanced pharmacy practice experience at a referral hospital in Kenya were reviewed and classified according to type of intervention and therapeutic area. RESULTS: The Kenyan students documented more interventions than American students (16.7 vs. 12.0 interventions/day) and provided significantly more consultations regarding human immunodeficiency virus (HIV) and antibiotics. The top area of consultations provided by American students was cardiovascular diseases. CONCLUSIONS: American and Kenyan pharmacy students successfully providing clinical pharmacy consultations in a resource-constrained, acute-care practice setting suggests an important role for pharmacy students in the reconciliation of prescriber orders with medication administration records and in providing drug information.