Communicating with patients with disorders of consciousness by translating thoughts into light

we intend to show, for the first time, that fNIRS can be used to reliably communicate with disorders of consciousness patients. There are many practical challenges to resolve (which are common to both fNIRS and EEG) such as involuntary movements by the patient, variability in consciousness itself, physical distortion in the head (such as from trauma) and a person\u27s limited ability to perform repetitive mental tasks. We will focus on patients who have already demonstrated by fMRI that they can perform motor imagery activation and plan to study up to 20 such patients over the course of a year.https://ir.lib.uwo.ca/brainscanprojectsummaries/1026/thumbnail.jp

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

Infantile-Onset Multisystem Neurologic, Endocrine, and Pancreatic Disease: Case and Review

We report three brothers born to consanguineous parents of Syrian descent, with a homozygous novel c.324G\u3eA (p.W108) mutation in PTRH2 that encodes peptidyl-tRNA hydrolase 2, causing infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We describe the core clinical features of postnatal microcephaly, motor and language delay with regression, ataxia, and hearing loss. Additional features include epileptic seizures, pancreatic insufficiency, and peripheral neuropathy. Clinical phenotyping enabled a targeted approach to the investigation and identification of a novel homozygous nonsense mutation in PTRH2, c.324G\u3eA (p.W108). We compare our patients with those recently described and review the current literature for IMNEPD

The Potential Role of fNIRS in Evaluating Levels of Consciousness

Over the last few decades, neuroimaging techniques have transformed our understanding of the brain and the effect of neurological conditions on brain function. More recently, light-based modalities such as functional near-infrared spectroscopy have gained popularity as tools to study brain function at the bedside. A recent application is to assess residual awareness in patients with disorders of consciousness, as some patients retain awareness albeit lacking all behavioural response to commands. Functional near-infrared spectroscopy can play a vital role in identifying these patients by assessing command-driven brain activity. The goal of this review is to summarise the studies reported on this topic, to discuss the technical and ethical challenges of working with patients with disorders of consciousness, and to outline promising future directions in this field

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest

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

Temporal Lobe Epilepsy after Refractory Status Epilepticus: An Illustrative Case and Review of the Literature

New onset refractory status epilepticus (NORSE) is a relatively newly defined disease entity, where otherwise healthy individuals develop unrelenting seizures that do not respond to conventional anticonvulsant therapy and may require months of therapy with anesthetic drugs. We have described a case of NORSE who subsequently developed mesial temporal lobe sclerosis (MTS) and recurrent temporal lobe seizures. We discuss the possible pathophysiological mechanisms by which refractory seizures may contribute to the development of temporal lobe epilepsy (TLE)

Cortical function in acute severe traumatic brain injury and at recovery: A longitudinal fMRI case study

Differences in the functional integrity of the brain from acute severe brain injury to subsequent recovery of consciousness have not been well documented. Functional magnetic resonance imaging (fMRI) may elucidate this issue as it allows for the objective measurement of brain function both at rest and in response to stimuli. Here, we report the cortical function of a patient with a severe traumatic brain injury (TBI) in a critically ill state and at subsequent functional recovery 9-months post injury. A series of fMRI paradigms were employed to assess sound and speech perception, command following, and resting state connectivity. The patient retained sound perception and speech perception acutely, as indexed by his fMRI responses. Command following was absent acutely, but was present at recovery. Increases in functional connectivity across multiple resting state networks were observed at recovery. We demonstrate the clinical utility of fMRI in assessing cortical function in a patient with severe TBI. We suggest that hallmarks of the recovery of consciousness are associated with neural activity to higher-order cognitive tasks and increased resting state connectivity

Assessing the consistency and sensitivity of the neural correlates of narrative stimuli using functional near-infrared spectroscopy

The neural correlates of narrative stimuli have facilitated research into the higher-order cognitive processes evoked when participants engage with complex, 'real-world' stimuli. These neural correlates have been successfully applied to measure higher-order cognitive processes in groups where behavioural evidence alone is inadequate, such as in clinical and developmental populations. While this research has been primarily conducted in fMRI and EEG, whether functional near-infrared spectroscopy (fNIRS) can reliably detect these neural correlates at an individual level, which is required for effective use in these populations, has yet to be established. This study replicated widespread inter-subject correlations (ISCs) in the frontal, parietal and temporal cortices in fNIRS in healthy participants when they watched part of the movie Bang! You're Dead and listened to an audio clip from the movie Taken. Conversely, these ISCs were primarily restricted to temporal cortices when participants viewed scrambled versions of those clips. Next, to assess whether these results were reliable at the single-participant level, two follow-up analyses were conducted. First, the consistency analysis compared each participant's ISCs against group results that excluded that individual. This approach found that 24/26 participants in Bang! You're Dead and 20/26 participants in Taken were statistically similar to the group. Second, the sensitivity analysis measured whether machine learning algorithms could decode between intact conditions and their scrambled counterparts. This approach yielded balanced accuracy scores of 81% in Bang! You're Dead and 79% in Taken. Overall, the neural correlates of narrative stimuli, as assessed by fNIRS, are reproducible across participants, supporting its broad application to clinical and developmental populations