Electronic Thesis and Dissertation Repository

Thesis Format

Alternative Format

Degree

Master of Science

Program

Neuroscience

Supervisor

Menon, Ravi

2nd Supervisor

Pruszynski, Andrew

Abstract

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to measure a proxy of neural activity in vivo with high spatial specificity. One subject can be followed for a long period of time to assess changes in functional brain organization. However, fMRI is extremely sensitive to motion. The challenges of training non-human primates to reduce motion in an MRI scanner motivate the study of anesthesia which is commonly used to substitute for this training. In this thesis, I compare three different commonly used anesthetic protocols: isoflurane, propofol-fentanyl in combination, and fentanyl alone, to test which of these best preserves a Blood Oxygen Level Dependent (BOLD) response to visual and somatosensory sensory stimuli in two rhesus macaque (Macaca mulatta) monkeys. In one animal, somatosensory responses were equally robust under propofol-fentanyl and fentanyl anesthesia but in the other animal, these responses were only robust under propofol-fentanyl. Somatosensory and visual responses were not observed under isoflurane anesthesia for either animal. It was under fentanyl and combinations with fentanyl that both sensory modalities appeared to best-elicit sensory related BOLD signals in these animals suggesting they should be further studied in a larger cohort.

Summary for Lay Audience

Functional magnetic resonance imaging (fMRI) is a technique that researchers can use to non-invasively measure which areas of the brain are active. This means that animal models, such as monkeys, and humans can easily be used as subjects for studies that use fMRI to measure brain activity during different types of activities. This is especially useful for studying how the brain changes over time after an injury as the brain is known to reorganize its processing functions in order to adapt or to heal. However, studying these injuries is difficult to do in humans because there is usually no before-injury fMRI report available for patients and injuries between patients vary widely in their degree. As a result, animal models, especially animal models such as non-human primates that have very similar sensory systems as human beings, are a valid alternative for such studies. Although NHPs have been successfully used in a variety of studies where they were kept awake, they are very challenging to train to enter an MRI scanner with limited movement. In fMRI studies, even slight motion from the subject can obscure the signal researchers are trying to measure. Anesthesia is commonly used by researchers to overcome this training challenge which would permit large cohorts of animals for studies about brain plasticity, but it is unclear which anesthetic protocol is most optimal to use for these studies. This investigation compares three common anesthetic protocols for non-human primate brain imaging to evaluate the robustness of the sensory signal that can be measured under each protocol. It was found that fentanyl was the anesthetic protocol under which the animals had the most robust brain response to visual and touch stimulation. This investigation offers a model for continued exploration of anesthetics so that the process of anesthetized fMRI studies of primates can be most effectively used for studying how the brain changes following injury and how it heals.

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