Electroencephalography (EEG) may aid physicians in identifying levels of consciousness in patients with limited or no behavioral responses, new research suggests.
For some patients with distinct EEG patterns, fMRI revealed activity that mirrored that of healthy volunteers. The activity differed from that of patients in a vegetative or minimally conscious state.
"The main implications of our findings are that patients who harbor the cognitive capacity to carry out fMRI mental imagery tasks are biologically different," study author Nicholas D. Schiff, MD, professor of neuroscience at the Feil Family Brain and Mind Research Institute of the Weill Cornell Medical College, New York City, told Medscape Medical News.
The study also showed "the integrity of cortical speech processing mechanisms in their EEG signals," he added.
These findings suggest that EEG may offer a cost-effective and efficient method of identifying patients who are cognitively aware but are unable to respond. More broadly, the investigators note that the findings underscore the importance of rethinking the way patients with severe brain injury are assessed.
"These findings emphasize the urgency to screen and identify patients who may be trapped in their heads and treated as unconscious," Schiff said in a release.
The study was published online November 21 in Current Biology.
New Guideline Awareness
The investigators measured delays in EEG brain responses to speech among 21 patients with behaviorally diagnosed disorders of consciousness and 13 volunteers who acted as the healthy control group. This approach helped them identify patients with preserved high-level cognitive abilities, including people with cognitive motor dissociation (CMD).
"We use the term 'cognitive motor dissociation' to label patients who appear unable to follow commands but [are] aware or unconscious at the bedside, and yet demonstrate successful fMRI mental imagery tasks as evidence of understanding and carrying out commands," Schiff said.
"Our study underscores the importance of rethinking the assessment of such patients" in light of recent guidelines for the treatment and evaluation of patients with disorders of consciousness following severe brain injuries, he added.
The American Academy of Neurology (AAN) collaborated with other professional groups to develop the guidelines, which were released in August 2018.
These recommendations address optimal treatment settings and diagnostic approaches. The guidelines recommend that more than one examination of consciousness be conducted. The guidelines also recommend, "in the event of continued ambiguity, use [of] multimodal imaging and electrophysiologic evaluations to assess for evidence of awareness."
Schiff said that the EEG technique not only holds promise for screening, but it could also help clarify diagnoses for families of unresponsive patients.
"It has become increasingly clear in the published literature that general clinical evaluation of patients with disorders of consciousness is often inaccurate," he said. "Studies have shown that approximately 40% of patients with signs of consciousness are missed on standard external assessments."
Medscape Medical News previously reported on individual cases that were misdiagnosed with use of positron-emission tomography and other methods.
EEG Advantages
Schiff and colleagues reclassified 10 participants with relevant fMRI activity. Medical records from external institutions indicated that five patients were in a vegetative state, two were in a minimally conscious state, and three had emerged from a minimally conscious state.
"Our findings support the inference that fMRI CF+ [command following–positive] responses identify patients with more preserved cerebral function than is typically present in vegetative state and minimally conscious state patients," the researchers write.
Additional advantages of the EEG strategy are that it is cost-effective and easy to use, Schiff said.
"EEG is virtually universally available in most clinical settings, which is not the case for other methods used in the assessment of disorders of consciousness, such as positron-emission tomography" or fMRI, he added.
Previous research suggests that in some unresponsive patients, general brain metabolic activity and overall patterns of sleep and wake electrical activity are preserved.
For example, in one study, patients with severe brain injury were assessed with transcranial magnetic stimulation (TMS) and high-density EEG. The investigators reported a graded correlation between these quantitative measures and bedside behavior.
The same research team found that a single EEG value produced during TMS, the pertubational complexity index (PCI), could distinguish minimally conscious patients from those in a vegetative state.
Schiff and colleagues note, however, that this study did not involve sensory input.
Other investigators took the PCI measure a step further, demonstrating that it can reflect a graded shift across a full range of disorders of consciousness.
"Our findings extend these results and reinforce the idea that such patients are better considered in a separate category when bedside examinations show no, or only very limited, evidence of awareness," Schiff said.
"Natural Speech Envelope"
The human brain produces electrical activity when following variations in sound wave intensity in speech. The current researchers assessed this "natural speech envelope" (NSE) with EEG while unresponsive participants listened to personally meaningful narratives recorded by family members.
The investigators also measured EEG results among healthy participants while they heard an excerpt from the novel Alice's Adventures in Wonderland.
"We chose this particular narrative because it has been used in the linguistics community and in other cognitive neuroscience studies for many purposes, allowing future work to examine other comparisons," Schiff said.
During fMRI of the 21 participants with brain injuries, 10 demonstrated statistically significant brain activity compared with brain activity in their resting state.
For this task, the researchers asked the patients to imagine they were playing tennis or attempting to open and close their right hand, for example. There were no differences in EEG lag time between these 10 patients and the healthy control group.
"It is the fMRI-based mental imagery that verifies awareness and cognition together through the demonstration of internal activity within the brain that is specific to the request command presented verbally; for example, 'imagine yourself playing tennis,' " Schiff explained.
Not only did the strategy detect cognition in this subset of patients, their average EEG NSE response delays to verbal commands allowed the researchers to place participants into distinct diagnostic categories.
"We find that the preservation of normal processing speed...correlated with an independent measurement of preserved cognitive function, the fMRI-based mental imagery responses," Schiff said.
Key Signals
The NSE findings aligned in a graded fashion with the behavioral diagnoses. The healthy control group showed the earliest NSE responses, whereas the minimally conscious and vegetative-state patients showed the most delayed latency responses.
The EEG electrodes were placed on the scalp in cluster 1 (CL1) and cluster 2 (CL2). Compared with the healthy participants, the delay in the CL1 readings was significant for patients who emerged from a minimally cognitive state (P = .034), those in a minimally cognitive state (MCS; P < .001), and those in a vegetative state (VS; P < .001).
In addition, compared with the patients who showed command-following activity on fMRI, the C1 component was significantly delayed among the MCS and VS patients (both comparisons, P < .001).
Similarly, a post hoc analysis showed that the CL2 response was significantly delayed among MCS and VS patients compared with the healthy control group (for both comparisons, P < .001). Likewise, compared with the fMRI-positive group, the CL2 reading was significantly delayed for the MCS (P = .001) and VS (P < .001) participants.
There were no statistically significant differences in the latencies of the CL1 and CL2 components between the healthy participants and the fMRI command-following patients.
Clinical Implications
The preservation of NSE latencies most likely correlates with a wide preservation of brain networks that support sustained attention, working memory, and other task-related cognitive processes, the researchers note.
"Thus, the NSE may be utilized as a screening tool to better allocate the resource of MRI investigations in patients without behavioral command following," they write.
"Our results also imply that the NSE can be developed as a screening tool to identify CMD patients," Schiff added.
Larger studies need to validate the findings, he noted.
"It is clear that this is a way forward to identify people quickly who may be trapped in their heads with high levels of awareness and little or no behavioral evidence of these capacities," he said. "Auditory processing is often preserved, making this likely more sensitive."
With regard to future research, "we plan to seek support to test the NSE as a measure to screen large numbers of patients for hidden cognitive capacities and to work toward developing new methods to help those patients we have already identified improve their ability to interact with the outside world," Schiff said.
Proxy for Preserved Cognitive Awareness?
Commenting on the findings for Medscape Medical News, Joseph T. Giacino, PhD, director of rehabilitation neuropsychology and of the SRN Disorders of Consciousness Program at Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, said that the graded relationship between level of consciousness and NSE latencies on EEG, as well as the NSE latencies that were indistinguishable from healthy control persons in all patients with positive fMRI findings, "suggest that the NSE latency may be a proxy for preserved conscious awareness that cannot be detected with behavioral testing.
"Because the NSE latency is technically easy to acquire and task demands are of low cognitive complexity, it offers clinicians a promising new tool that may have higher clinical and practical utility than fMRI," added Giacino, who was lead author of the 2018 guideline updates from the AAN and other societies.
At the same time, it is important to note that the predictive validity of NSE latency remains unclear, Giacino said.
Unanswered questions, he noted, include the following:
For acutely injured patients, can this index be used to predict subsequent functional recovery?
For patients in the chronic phase, will it help identify those most likely to benefit from augmentative communication technologies?
Also commenting on the findings, Elizaveta Lazeva, MD, neurologist at the Research Center of Neurology in Moscow, Russia, told Medscape Medical News that the testing strategy needs more verification.
"I don't think that NSE can be used as a tool for differential diagnosis of VS and MCS. But it is absolutely clear that it may be applicable for choosing patients for brain-computer interface [BCI] research and for improvement of BCI technology in patients with disorders of consciousness," she said.
"I think BCI could be a very important part of rehabilitation of these patients, so I will be very interested in future research," she added.
Lazeva did question the study's finding that two of the three patients who had emerged from the minimally cognitive state had fluent speech. In her experience, "fluent speech means clear consciousness but not a disorder of consciousness," she said. However, she added that this discrepancy is minor and "not critical for the whole study."
In a study published earlier this year, Lazeva and colleagues evaluated a Russian version of the Coma Recovery Scale–Revised. They reported a high level of consistency, sensitivity, and validity of this scale in assessing patients with chronic disorders of consciousness.
The study was funded by grant from the National Institutes of Health, by a National Science Foundation graduate research fellowship, and by the National Institute of Child Health and Development, the James S. McDonnell Foundation, the Jerold B. Katz Foundation, and the Weill Cornell Center for Translational Sciences. Dr Schiff has submitted a patent related to this research. Dr Giacino and Dr Lazeva have reported no relevant financial relationships.
Curr Biol. Published online November 21, 2018. Full text
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Cite this: EEG May Identify Consciousness in Severely Brain-Injured Patients - Medscape - Dec 05, 2018.
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