Conscious processing of narrative stimuli synchronizes heart rate between individuals.

Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes synchronize between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of heart rate (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with our hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and higher ISC-HR predicts better recall of the narrative. Finally, patients with disorders of consciousness have lower ISC-HR, as compared to healthy individuals. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.

A hierarchy of event-related potential markers of auditory processing in disorders of consciousness.

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.

Risk, diagnostic error, and the clinical science of consciousness.

In recent years, a number of new neuroimaging techniques have detected covert awareness in some patients previously thought to be in a vegetative state/unresponsive wakefulness syndrome. This raises worries for patients, families, and physicians, as it indicates that the existing diagnostic error rate in this patient group is higher than assumed. Recent research on a subset of these techniques, called active paradigms, suggests that false positive and false negative findings may result from applying different statistical methods to patient data. Due to the nature of this research, these errors may be unavoidable, and may draw into question the use of active paradigms in the clinical setting. We argue that false positive and false negative findings carry particular moral risks, which may bear on investigators' decisions to use certain methods when independent means for estimating their clinical utility are absent. We review and critically analyze this methodological problem as it relates to both fMRI and EEG active paradigms. We conclude by drawing attention to three common clinical scenarios where the risk of diagnostic error may be most pronounced in this patient group.

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 patient's level of residual cognition and awareness.

The reliability of the N400 in single subjects: implications for patients with disorders of consciousness.

Functional neuroimaging assessments of residual cognitive capacities, including those that support language, can improve diagnostic and prognostic accuracy in patients with disorders of consciousness. Due to the portability and relative inexpensiveness of electroencephalography, the N400 event-related potential component has been proposed as a clinically valid means to identify preserved linguistic function in non-communicative patients. Across three experiments, we show that changes in both stimuli and task demands significantly influence the probability of detecting statistically significant N400 effects - that is, the difference in N400 amplitudes caused by the experimental manipulation. In terms of task demands, passively heard linguistic stimuli were significantly less likely to elicit N400 effects than task-relevant stimuli. Due to the inability of the majority of patients with disorders of consciousness to follow task commands, the insensitivity of passive listening would impede the identification of residual language abilities even when such abilities exist. In terms of stimuli, passively heard normatively associated word pairs produced the highest detection rate of N400 effects (50% of the participants), compared with semantically-similar word pairs (0%) and high-cloze sentences (17%). This result is consistent with a prediction error account of N400 magnitude, with highly predictable targets leading to smaller N400 waves, and therefore larger N400 effects. Overall, our data indicate that non-repeating normatively associated word pairs provide the highest probability of detecting single-subject N400s during passive listening, and may thereby provide a clinically viable means of assessing residual linguistic function. We also show that more liberal analyses may further increase the detection-rate, but at the potential cost of increased false alarms.

Complexity and familiarity enhance single-trial detectability of imagined movements with electroencephalography.

OBJECTIVE: We sought to determine whether the sensorimotor rhythms (SMR) elicited during motor imagery (MI) of complex and familiar actions could be more reliably detected with electroencephalography (EEG), and subsequently classified on a single-trial basis, than those elicited during relatively simpler imagined actions. METHODS: Groups of healthy volunteers, including experienced pianists and ice hockey players, performed MI of varying complexity and familiarity. Their electroencephalograms were recorded and compared using brain-computer interface (BCI) approaches and spectral analyses. RESULTS: Relative to simple MI, significantly more participants produced classifiable SMR for complex MI. During MI of performance of a complex musical piece, the EEG of the experienced pianists was classified significantly more accurately than during MI of performance of a simpler musical piece. The accuracy of EEG classification was also significantly more sustained during complex MI. CONCLUSION: MI of complex actions results in EEG responses that are more reliably classified for more individuals than MI of relatively simpler actions, and familiarity with actions enhances these responses in some cases. SIGNIFICANCE: The accuracy of SMR-based BCIs in non-communicative patients may be improved by employing familiar and complex actions. Increased sensitivity to MI may also improve diagnostic accuracy for severely brain-injured patients in a vegetative state.

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.

Temporally and functionally dissociable retrieval processing operations revealed by event-related potentials.

In a pair of recent studies, frontally distributed event-related potential (ERP) indices of two distinct post-retrieval processes were identified. It has been proposed that one of these processes operates over any kinds of task relevant information in service of task demands, while the other operates selectively over recovered contextual (episodic) information. The experiment described here was designed to test this account, by requiring retrieval of different kinds of contextual information to that required in previous relevant studies. Participants heard words spoken in either a male or female voice at study and ERPs were acquired at test where all words were presented visually. Half of the test words had been spoken at study. Participants first made an old/new judgment, distinguishing via key press between studied and unstudied words. For words judged 'old', participants indicated the voice in which the word had been spoken at study, and their confidence (high/low) in the voice judgment. There was evidence for only one of the two frontal old/new effects that had been identified in the previous studies. One possibility is that the ERP effect in previous studies that was tied specifically to recollection reflects processes operating over only some kinds of contextual information. An alternative is that the index reflects processes that are engaged primarily when there are few contextual features that distinguish between studied stimuli.