Identifying Electrophysiological Components of Covert Awareness in Patients with Disorders of Consciousness

Naturalistic stimuli evoke synchronous patterns of neural activity between individuals in sensory and higher cognitive, “executive” networks of the brain. fMRI paradigms developed to measure this inter-subject synchronization have been extended to test for executive processing in behaviourally non-responsive patients as a neural marker of awareness. This thesis adapted one such paradigm for use in EEG, a low-cost, portable neuroimaging technique that can be administered at a patient’s bedside. Healthy participants listened to a suspenseful auditory narrative during EEG recording. Significant inter-subject synchronization was found throughout the audio but was significantly reduced during a scrambled control condition. This paradigm was then used to evaluate executive processing in a cohort of patients. One locked-in patient and one patient in a vegetative state were significantly synchronized to healthy controls during the audio. EEG is a suitable tool to detect executive processing, a proxy measure of awareness, in patients who are behaviourally non-responsive

Individualized assessment of residual cognition in patients with disorders of consciousness

Patients diagnosed with disorders of consciousness show minimal or inconsistent behavioural evidence of conscious awareness. However, using functional neuroimaging, recent research in clinical neuroscience has identified a subpopulation of these patients who reliably produce neural markers indicative of awareness. In this study, we recorded electroencephalograms during a response-free movie task to assess narrative processing in patients with disorders of consciousness. Thirteen patients diagnosed with a disorder of consciousness and 28 healthy controls participated in this study. We designed a movie-watching/listening paradigm involving two suspenseful movie clips, one audiovisual and one audio-only, and used electroencephalography to extract patterns of brain activity that were maximally correlated between subjects. These activity patterns served as electrophysiological indices of narrative processing, which were compared to the neural responses of patients during the same movies. Our analysis revealed two patterns of neural activity, one for each movie condition, that were significantly and reliably correlated between healthy participants. Of the twelve patients who watched the audiovisual movie, 25% produced a pattern of activity that was significantly correlated with the healthy group, while of the ten who listened to the audio narrative, 30% produced electrophysiological patterns similar to controls (one patient responded appropriately to both). The method presented here allows for rapid bedside assessment of higher-order cognitive processing in patients with disorders of consciousness. By leveraging the common neural response to movie stimuli, we were able to identify comparable patterns of brain activity in individual, behaviourally non-responsive patients, reflecting a capacity for narrative processing

Late positive complex in event-related potentials tracks memory signals when they are decision relevant.

The Late Positive Complex (LPC) is an Event-Related Potential (ERP) consistently observed in recognition-memory paradigms. In the present study, we investigated whether the LPC tracks the strength of multiple types of memory signals, and whether it does so in a decision dependent manner. For this purpose, we employed judgements of cumulative lifetime exposure to object concepts, and judgements of cumulative recent exposure (i.e., frequency judgements) in a study-test paradigm. A comparison of ERP signatures in relation to degree of prior exposure across the two memory tasks and the study phase revealed that the LPC tracks both types of memory signals, but only when they are relevant to the decision at hand. Another ERP component previously implicated in recognition memory, the FN400, showed a distinct pattern of activity across conditions that differed from the LPC; it tracked only recent exposure in a decision-dependent manner. Another similar ERP component typically linked to conceptual processing in past work, the N400, was sensitive to degree of recent and lifetime exposure, but it did not track them in a decision dependent manner. Finally, source localization analyses pointed to a potential source of the LPC in left ventral lateral parietal cortex, which also showed the decision-dependent effect. The current findings highlight the role of decision making in ERP markers of prior exposure in tasks other than those typically used in studies of recognition memory, and provides an initial link between the LPC and the previously suggested role of ventral lateral parietal cortex in memory judgements

Ethics of non-Therapeutic research on imminently dying patients in the intensive care unit

Non-Therapeutic research with imminently dying patients in intensive care presents complex ethical issues. The vulnerabilities of the imminently dying, together with societal disquiet around death and dying, contribute to an intuition that such research is beyond the legitimate scope of scientific inquiry. Yet excluding imminently dying patients from research hinders the advancement of medical science to the detriment of future patients. Building on existing ethical guidelines for research, we propose a framework for the ethical design and conduct of research involving the imminently dying. To enable rapid translation to practice, we frame the approach in the form of eight ethical questions that researchers and research ethics committees ought to answer prior to conducting any research with this patient population. (1) Does the study hypothesis require the inclusion of imminently dying patients? (2) Are non-Therapeutic risks and burdens minimised consistent with sound scientific design? (3) Are the risks of these procedures no more than minimal risk? (4) Are these non-Therapeutic risks justified insofar as they are reasonable in relation to the anticipated benefits of the study? (5) Will valid informed consent be obtained from an authorised surrogate decision maker? (6) How will incidental findings be handled? (7) What additional steps are in place to protect families and significant others of research participants? (8) What additional steps are in place to protect clinical staff and researchers? Several ethical challenges hinder research with imminently dying patients. Nonetheless, provided adequate protections are in place, non-Therapeutic research with imminently dying patients is ethically justifiable. Applying our framework to an ongoing study, we demonstrate how our question-driven approach is well suited to guiding investigators and research ethics committees

Exploring electroencephalography with a model inspired by quantum mechanics.

An outstanding issue in cognitive neuroscience concerns how the brain is organized across different conditions. For instance, during the resting-state condition, the brain can be clustered into reliable and reproducible networks (e.g., sensory, default, executive networks). Interestingly, the same networks emerge during active conditions in response to various tasks. If similar patterns of neural activity have been found across diverse conditions, and therefore, different underlying processes and experiences of the environment, is the brain organized by a fundamental organizational principle? To test this, we applied mathematical formalisms borrowed from quantum mechanisms to model electroencephalogram (EEG) data. We uncovered a tendency for EEG signals to be localized in anterior regions of the brain during "rest", and more uniformly distributed while engaged in a task (i.e., watching a movie). Moreover, we found analogous values to the Heisenberg uncertainty principle, suggesting a common underlying architecture of human brain activity in resting and task conditions. This underlying architecture manifests itself in the novel constant KBrain, which is extracted from the brain state with the least uncertainty. We would like to state that we are using the mathematics of quantum mechanics, but not claiming that the brain behaves as a quantum object

Protocol for the Prognostication of Consciousness Recovery Following a Brain Injury

Individuals who have suffered a severe brain injury typically require extensive hospitalization in intensive care units (ICUs), where critical treatment decisions are made to maximize their likelihood of recovering consciousness and cognitive function. These treatment decisions can be difficult when the neurological assessment of the patient is limited by unreliable behavioral responses. Reliable objective and quantifiable markers are lacking and there is both (1) a poor understanding of the mechanisms underlying the brain’s ability to reconstitute consciousness and cognition after an injury and (2) the absence of a reliable and clinically feasible method of tracking cognitive recovery in ICU survivors. Our goal is to develop and validate a clinically relevant EEG paradigm that can inform the prognosis of unresponsive, brain-injured patients in the ICU. This protocol describes a study to develop a point-of-care system intended to accurately predict outcomes of unresponsive, brain-injured patients in the ICU. We will recruit 200 continuously-sedated brain-injured patients across five ICUs. Between 24 h and 7 days post-ICU admission, high-density EEG will be recorded from behaviorally unresponsive patients before, during and after a brief cessation of pharmacological sedation. Once patients have reached the waking stage, they will be asked to complete an abridged Cambridge Brain Sciences battery, a web-based series of neurocognitive tests. The test series will be repeated every day during acute admission (ICU, ward), or as often as possible given the constraints of ICU and ward care. Following discharge, patients will continue to complete the same test series on weekly, and then monthly basis, for up to 12 months following injury. Functional outcomes will also be assessed up to 12 months post-injury. We anticipate our findings will lead to an increased ability to identify patients, as soon as possible after their brain injury, who are most likely to survive, and to make accurate predictions about their long-term cognitive and functional outcome. In addition to providing critically needed support for clinical decision-making, this study has the potential to transform our understanding of key functional EEG networks associated with consciousness and cognition

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements