Damian Cruse

A Role for the Default Mode Network in the Bases of Disorders of Consciousness

Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity.

Detecting Awareness in the Vegetative State: Electroencephalographic Evidence for Attempted Movements to Command

Patients in the Vegetative State (VS) do not produce overt motor behavior to command and are therefore considered to be unaware of themselves and of their environments. However, we recently showed that high-density electroencephalography (EEG) can be used to detect covert command-following in some VS patients. Due to its portability and inexpensiveness, EEG assessments of awareness have the potential to contribute to a standard clinical protocol, thus improving diagnostic accuracy. However, this technique requires refinement and optimization if it is to be used widely as a clinical tool. We asked a patient who had been repeatedly diagnosed as VS for 12-years to try to move his left and right hands, between periods of rest, while EEG was recorded from four scalp electrodes. We identified appropriate and statistically reliable modulations of sensorimotor beta rhythms following commands to try to move, which could be significantly classified at a single-trial level. These reliable effects indicate that the patient attempted to follow the commands, and was therefore aware, but was unable to execute an overtly discernable action. The cognitive demands of this novel task are lower than those used previously and, crucially, allow for awareness to be determined on the basis of a 20-minute EEG recording made with only four electrodes. This approach makes EEG assessments of awareness clinically viable, and therefore has potential for inclusion in a standard assessment of awareness in the VS.

Brain–computer interfaces for communication with nonresponsive patients

A substantial number of patients who survive severe brain injury progress to a nonresponsive state of wakeful unawareness, referred to as a vegetative state (VS). They appear to be awake, but show no signs of awareness of themselves, or of their environment in repeated clinical examinations. However, recent neuroimaging research demonstrates that some VS patients can respond to commands by willfully modulating their brain activity according to instruction. Brain–computer interfaces (BCIs) may allow such patients to circumvent the barriers imposed by their behavioral limitations and communicate with the outside world. However, although such devices would undoubtedly improve the quality of life for some patients and their families, developing BCI systems for behaviorally nonresponsive patients presents substantial technical and clinical challenges. Here we review the state of the art of BCI research across noninvasive neuroimaging technologies, and propose how such systems should be developed further to provide fully fledged communication systems for behaviorally nonresponsive populations. Ann Neurol 2012;72:312–323

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.

Brain–computer interfacing in disorders of consciousness

Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential for the development of simple brain–computer interfaces (BCI) as a diagnosis in behaviourally unresponsive patients. Objectives: This study here reviews current EEG-based BCIs that hold potential for assessing and eventually assisting patients with DoC. It highlights key areas for further development that might eventually make their application feasible in this challenging patient group. Methods: The major types of BCIs proposed in the literature are considered, namely those based on the P3 potential, sensorimotor rhythms, steady state oscillations and slow cortical potentials. In each case, a brief overview of the relevant literature is provided and then their relative merits for BCI applications in DoC are considered. Results: A range of BCI designs have been proposed and tested for enabling communication in fully conscious, paralysed patients. Although many of these have potential applicability for patients with DoC, they share some key challenges that need to be overcome, including limitations of stimulation modality, feedback, user training and consistency. Conclusion: Future work will need to address the technical and practical challenges facing reliable implementation at the patients bedside.

Prefrontal cortex contributions to episodic retrieval monitoring and evaluation

Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation - the right-frontal ERP old/new effect - which is thought to reflect activity in PFC. The functional significance of this old/new effect remains a matter of debate, and this study was designed to test two accounts: (i) that the effect indexes processes linked to the monitoring or evaluation of the products of retrieval in service of task demands, or (ii) that it indexes the number of internal decisions required for a task judgment. Participants studied words in one of two colours. In a subsequent retrieval task, old (studied) and new words were presented in a neutral colour. Participants made initial old/new judgments, along with study colour judgments to words thought to be old. They also indicated their confidence (high/low) in the colour decision. Right-frontal ERP old/new effects were larger for high than for low confidence correct colour judgments, and the magnitude of the right-frontal effect was correlated with the proportions of low confidence judgments that were made. Because the numbers of decisions associated with these response categories are equivalent, these findings do not support a decision-based account of the right-frontal ERP old/new effect. Rather, the correlation between confidence and the magnitude of the effect links it with retrieval monitoring and evaluation processes.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

BackgroundThe rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness.MethodsfMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits.ResultsfMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus.ConclusionsThese results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

Consciousness revealed: new insights into the vegetative and minimally conscious states

PURPOSE OF REVIEW In recent years, the results of neuroimaging studies have fundamentally changed the way we think about the vegetative and minimally conscious states. RECENT FINDINGS Functional MRI studies have demonstrated that some high-level cognitive functions, such as language comprehension and target detection, are preserved in a subset of patients with disorders of consciousness. Similar methods have even allowed a patient who was assumed to be in a vegetative state to communicate. PET has provided insights into similarities and differences in the ways in which pain is processed by this patient group, whereas electrophysiological methods have revealed further evidence of awareness as well as learning. SUMMARY The prognostic and diagnostic information provided by these new approaches clearly argues for their future use alongside conventional assessment techniques. By demonstrating that a behaviourally unresponsive patient could communicate by means of his/her thoughts using functional MRI, these new techniques open up a new direction of research into the development of more sophisticated communication devices that may be used more generally by these patients. In our opinion, such devices, employing electroencephalograph among other techniques, may soon allow for patients who retain sufficient cognitive abilities to communicate, to do so outside of an MRI scanner.

Multiple tasks and neuroimaging modalities increase the likelihood of detecting covert awareness in patients with disorders of consciousness

Minimal or inconsistent behavioral responses to command make it challenging to accurately diagnose the level of awareness of a patient with a Disorder of consciousness (DOC). By identifying markers of mental imagery being covertly performed to command, functional neuroimaging (fMRI), electroencephalography (EEG) has shown that some of these patients are aware despite their lack of behavioral responsiveness. We report the findings of behavioral, fMRI, and EEG approaches to detecting command-following in a group of patients with DOC. From an initial sample of 14 patients, complete data across all tasks was obtained in six cases. Behavioral evaluations were performed with the Coma Recovery Scale—Revised. Both fMRI and EEG evaluations involved the completion of previously validated mental imagery tasks—i.e., motor imagery (EEG and fMRI) and spatial navigation imagery (fMRI). One patient exhibited statistically significant evidence of motor imagery in both the fMRI and EEG tasks, despite being unable to follow commands behaviorally. Two behaviorally non-responsive patients produced appropriate activation during the spatial navigation fMRI task. However, neither of these patients successfully completed the motor imagery tasks, likely due to specific motor area damage in at least one of these cases. A further patient demonstrated command following only in the EEG motor imagery task, and two patients did not demonstrate command following in any of the behavioral, EEG, or fMRI assessments. Due to the heterogeneity of etiology and pathology in this group, DOC patients vary in terms of their suitability for some forms of neuroimaging, the preservation of specific neural structures, and the cognitive resources that may be available to them. Assessments of a range of cognitive abilities supported by spatially-distinct brain regions and indexed by multiple neural signatures are therefore required in order to accurately characterize a patients level of residual cognition and awareness.

Lies, damned lies and diagnoses: estimating the clinical utility of assessments of covert awareness in the vegetative state.

Abstract Background: Functional neuroimaging of patients in the vegetative state has been shown to provide diagnostic and prognostic information beyond that which conventional behavioural assessments may allow. However, before these promising approaches may reach large numbers of patients through a standard clinical protocol, it is necessary to determine the utility of these assessments—i.e. the accuracy of their diagnoses. Methods and results: This study demonstrated that, due to the nature of statistical testing and the absence of a ‘ground truth’ of consciousness, it is impossible to calculate the conventional measures of clinical utility—sensitivity and specificity—for diagnoses made on the basis of functional neuroimaging for command-following. Nevertheless, it is crucial for such measures to be determined in order for valuable clinical resources to be distributed wisely. Therefore, a number of alternative guidelines are offered for the estimation of clinical utility. Conclusions: By evaluating new and existing functional neuroimaging methods against the proposed guidelines, this study argues that it may be possible to achieve dramatically and efficiently improved diagnostic and prognostic accuracy for all vegetative state patients.