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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

St. Lawrence, Keith

2nd Supervisor

Owen, Adrian

Co-Supervisor

Abstract

Vegetative state (VS) is a disorder of consciousness often referred to as “wakefulness without awareness”. Patients in this condition experience normal sleep-wake cycles, but lack all awareness of themselves and their surroundings. Clinically, assessing consciousness relies on behavioural tests to determine a patient’s ability to follow commands. This subjective approach often leads to a high rate of misdiagnosis (~40%) where patients who retain residual awareness are misdiagnosed as being in a VS. Recently, functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI), has allowed researchers to use command-driven brain activity to infer consciousness. Although promising, the cost and accessibility of fMRI hinder its use for frequent examinations. Functional near-infrared spectroscopy (fNIRS) is an emerging optical technology that is a promising alternative to fMRI. The technology is safe, portable and inexpensive allowing for true bedside assessment of brain function.

This thesis focuses on using time-resolved (TR) fNIRS, a variant of fNIRS with enhanced sensitivity to the brain, to detect brain function in healthy controls and patients with disorders of consciousness (DOC). Motor imagery (MI) was used to assess command-driven brain activity since this task has been extensively validated with fMRI. The feasibility of TR-fNIRS to detect MI activity was first assessed on healthy controls and fMRI was used for validation. The results revealed excellent agreement between the two techniques with an overall sensitivity of 93% in comparison to fMRI. Following these promising results, TR-fNIRS was used for rudimentary mental communication by using MI as affirmation to questions. Testing this approach on healthy controls revealed an overall accuracy of 76%. More interestingly, the same approach was used to communicate with a locked-in patient under intensive care. The patient had residual eye movement, which provided a unique opportunity to confirm the fNIRS results. The TR-fNIRS results were in full agreement with the eye responses, demonstrating for the first time the ability of fNIRS to communicate with a patient without prior training. Finally, this approach was used to assess awareness in DOC patients, revealing residual brain function in two patients who had also previously shown significant MI activity with fMRI.

Summary for Lay Audience

In its most basic form, consciousness can be defined as the state of being ‘awake’ and ‘aware’ to one’s self and one’s surroundings. While determining if someone is awake is relatively simple, assessing awareness is not trivial. The current clinical practice relies on behavioural testing of patients to infer awareness, which often leads to a high rate (~40%) of misdiagnosis, since patients who retain cognitive function may be unable to physically or verbally respond to commands. Recently, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used to assess brain function in patients diagnosed as suffering from a disorder of consciousness (DOC). Instead of asking patients to physically or verbally follow commands, patients were asked to perform a certain mental task in respond to commands. One such task is motor imagery (MI), which activates specific areas in the brain associated with motor planning. Detecting this command-driven brain activity can therefore be used to infer awareness. Although promising, the cost and more importantly the accessibility of fMRI limit its use at the bedside. Functional near-infrared spectroscopy (fNIRS) is a promising optical technique that is safe, inexpensive and portable, allowing for bedside assessment of brain function.

To this end, the aim of this work was to develop an fNIRS system that can be used to assess brain function in DOC patients. The feasibility of this system was first assessed in a group of healthy participants prior to translating the technology to patients with brain injuries. Overall, our in-house built system provided excellent sensitivity to MI-related brain activity. Given these promising results, the next step was to use our system to communicate with a patient on life support who was unable to verbally communicate. By asking clinically relevant questions, and using MI for affirmation, we were able to establish binary mental communication with this patient. Finally, this technology was used to assess consciousness at the bedside in DOC patients. Two patients who were clinically diagnosed as showing no signs of awareness were able to produce command-driven brain activity, suggesting the presence of residual awareness.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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