Using anesthesia to predict recovery from disorders of consciousness
Catherine Duclos, PhD
The Research Institute of the McGill University Health Centre
Montreal, Québec, Canada
Catherine Duclos, PhD, Postdoctoral Fellow at The Research Institute of the McGill University Health Centre Assistant, Professor in the Department of Anesthesiology and Pain Medicine at the University of Montréal, and Researcher at Hôpital du Sacré-Coeur de Montréal, is setting out to uncover some of the intricacies of consciousness in hopes of improving patient prognostication and recovery with her 2021 IARS Mentored Research Award. Discover more about her journey to address this quandary and what she hopes to answer in the future.
1. Can you give me a brief overview of what it is you do in your daily work?
As a postdoctoral fellow who will soon be transitioning to a faculty/PI position, no two days are the same! In Dr. Stefanie Blain-Moraes’ lab, I’m involved in a few different projects, all of which are carried out in the Intensive Care Unit (ICU). Since we work with acutely brain-injured patients, we need to make contact with patients’ families quickly to obtain consent. Since I’ve been doing research in the ICU for 10 years, I’m the designated person who speaks with families about our studies, obtains consent (next of kin), and discusses with the attending physicians to ensure the clinical team is also on board with our study. We conduct high-density EEG at bedside, which is quite challenging: patients are unresponsive, often have severe injuries on their scalp, a missing bone flap or an external ventricular drain. We conduct EEG before, during and after a change in sedation status, which is sometimes accompanied by behavioral changes, agitation, etc. It’s a challenging but rewarding research setting for me and my colleagues. I also work with a group of anesthesiologists in the operating room, which is a research area I hope to expand upon in the coming years. Aside from patient recruitment and data acquisition, I still love being close to my data and carrying out data and statistical analyses. This spring, I also co-led (with Dr. Blain-Moraes) the organization of the 1st Canadian Consciousness Research Symposium, which virtually gathered 200 attendees from over 15 countries. This two-day event enabled researchers and clinicians to share their expertise on neural mechanisms of consciousness, sleep, dreaming, disorders of consciousness, delirium mediation, artificial intelligence, and pharmacologically-induced alterations in consciousness. I was proud to coordinate this event and initiate a new consciousness network that will continue to conduct research events in coming years. Finally, the last year has been filled with grant writing, paper writing and meetings with new collaborators to expand our studies across Canada. We’re working hard to design impactful studies that will be led across multiple adult and pediatric ICUs in the country.
2. Is there anyone else you wish to acknowledge as part of this research team?
Dr. Blain-Moraes is my supervisor and mentor. She is a wonderful inspiration, professionally and personally, and I am grateful that she has enabled me to develop this study under her supervision. I’d also like to acknowledge Charlotte Maschke, BSc, and Yacine Mahdid, BSc, who have played a pivotal role in the development of the Adaptive Reconfiguration Index, which we aim to validate in our study.
3. What drew you to this area of research?
My doctoral research focused on sleep and circadian rhythms in the acute phase of moderate to severe traumatic brain injury. My interest in sleep is what initially drew me to this area of research. With time, the similarities and differences between sleep and sedation/anesthesia have fascinated me more and more, and it became clear to me that I wished to pursue a postdoctoral fellowship in anesthesiology and consciousness. When I learned about Dr. Stefanie Blain-Moraes, who had just launched her lab at McGill University, I was thrilled! Even though she was a young professor and PI, I was impressed by her background and her research studies. I loved the way she framed her work around clinically-relevant questions, and it was the ideal fit for me to pursue my research as of 2018.
4. What is the goal of your research?
Loss of consciousness in response to anesthesia is accompanied by specific patterns of brain network reconfiguration. In patients with disorders of consciousness (DOC), who are unable to respond reliably to commands, the presence or absence of these anesthetic-induced reconfiguration patterns may reveal the patient’s underlying capacity for consciousness. Anesthesia may therefore be key to the development of an accurate prognostic measure for acute unresponsive patients. The current study aims to test the accuracy of an entirely new metric for the prognostication of consciousness recovery in coma and DOC – the Adaptive Reconfiguration Index (ARI), which quantifies brain network reconfiguration in response to propofol anesthesia, using high-density (128-channel) electroencephalography (EEG) – and to translate the ARI to a clinical-grade EEG system. Unlike other prognostic measures that rely on global or event-related brain signals, the ARI focuses on resting-state brain signals that are attenuated by the effects of general anesthesia, which putatively include those associated with conscious awareness. Our team has developed a novel within-subject paradigm that assesses brain networks and responses of patients with DOC using themselves as their own controls.
I aim to use a computational neuroscience approach to discover how functional brain networks drive altered states of consciousness, and how these networks can be modulated to improve health outcomes. To achieve this goal, I will use models of altered and/or pathological states of consciousness, including coma, anesthesia and sleep, and I will collaborate with computational neuroscience developers to apply cutting-edge techniques (e.g. machine learning, network dynamics and connectivity, information theory, graph theory) to study brain networks. I will also modulate states of altered consciousness to evaluate their impact on neuronal networks, and recovery of neurological and cognitive functions. My main hypothesis is that the oscillatory properties of altered states of consciousness can be modulated to optimize cognitive and functional outcomes in clinical populations.
5. What is the potential impact of your research on the field of anesthesia?
The proposed study is both novel and paradigm-shifting, because it introduces anesthesia as a neuromodulation technique to predict consciousness recovery in unresponsive patients in coma and DOC. Indeed, it will test the hypothesis that the brain’s response to propofol can be a marker of potential for consciousness. The proposed study has the potential to situate anesthesia as a prognostic tool for acute care and neurological patients, and to provide healthcare teams with a novel approach to refine patient prognosis. Establishing an accurate prognosis for recovery has major implications for patient treatment decisions, caregivers, and the healthcare system.
My research proposes to treat anesthesia as a neuromodulation tool to improve patient prognostication and recovery. More specifically, it will use network neuroscience to personalize medicine and continuous sedation, optimizing patient care and cognitive recovery.
6. How do you feel about receiving the IARS Mentored Research Award?
I feel extremely grateful to receive the IARS Mentored Research Award as I am about to transition to my faculty position. Very few non-clinicians have been awarded the IARS Mentored Research Award over the past years, and I feel privileged to be among them.
The IARS Mentored Research Award was the only grant I was eligible to apply for as a postdoctoral fellow, and I am grateful for its existence. Such a grant has enormous impact on early-career researchers, and undeniably raises their chances for success. Thank you to the IARS for this incredible support for a young researcher such as myself! I will be forever grateful that the IARS could support my research.
7. How will this award affect your research/professional trajectory?
This is my very first grant and will have a tremendous impact on the start of my career. The IARS Mentored Research Award will enable me to hire my first graduate student, and to improve my chances of obtaining my first salary award. Most importantly, it will propel our study forward as we will now be able to pursue patient recruitment and testing for 2 additional years. Importantly, I feel like this award is legitimizing my place in anesthesia research and confirming the clinical relevance of my research interests.
8. Once you complete this mentored research award, what’s next for you? What’s your vision for the future?
Once I complete this Mentored Research Award, I will be less than two years into my faculty position at the University of Montréal. This award will therefore be the stepping stone to building my lab and my research program in anesthesiology and critical care research. If I picture myself 10 years from now, I aim to be leading an internationally recognized lab that conducts clinically-relevant research that has made an impact on anesthesiology and critical care. I hope to have shown preliminary evidence that we can use network neuroscience to individualize anesthesia and continuous sedation, optimizing patient care and cognitive recovery.