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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Everling, Stefan

Abstract

Visually exploring the surrounding environment relies on attentional selection of behaviourally relevant stimuli for further processing. The prefrontal cortex contributes to target selection as part of a frontoparietal network that controls shifts of gaze and attention towards relevant stimuli. Evidence from stroke patients and nonhuman primate lesion studies have shown that unilateral damage to the prefrontal cortex commonly impairs the ability to allocate attention toward stimuli in the contralesional visual hemifield. Although these impairments often exhibit a gradual improvement over time, the neural plasticity that underlies recovery of function remains poorly understood. The main objective of this dissertation was to study the relationship between large-scale network reorganization and the recovery of lateralized target selection deficits. To that aim, endothelin-1 was used to produce unilateral ischemic lesions in the caudal lateral prefrontal cortex of four rhesus macaques. Longitudinal behavioural and neuroimaging data were collected before and after the lesions, including eye-tracking while monkeys performed free-choice and visually guided saccades, resting-state fMRI, and diffusion-weighted imaging. Chapter 2 investigated the effects of unilateral prefrontal cortex lesions on saccade target selection and oculomotor parameters to disentangle attentional and motor impairments in the lasting contralesional target selection deficit. Chapter 3 examined the resting-state functional reorganization in a frontoparietal network during recovery of contralesional target selection. Finally, Chapter 4 investigated microstructural changes in cortical white matter tracts from diffusion-weighted imaging after behavioural recovery compared to pre-lesion. In general, spatiotemporal patterns of functional and structural network reorganization differed based on the extent of prefrontal damage. Altogether, these studies characterized the recovery of lateralized target selection deficits in a macaque model of focal cerebral ischemia and demonstrated involvement of both contralesional and ipsilesional networks throughout behavioural recovery. The broad implication of this research is that a network perspective is fundamental to understanding compensatory mechanisms of brain reorganization underlying recovery of function.

Summary for Lay Audience

Exploring our surrounding environment involves continuous internal decisions about where to look. This ability to choose specific locations to look at out of many other options relies on a network of brain areas in the frontal and parietal cortex. Injury to one side of the brain that affects frontal-parietal areas usually impairs the ability to pay attention to and look toward the opposite side of space. For example, patients with a right-sided stroke may fail to apply make-up or shave the left half of their face, leave uneaten food on the left side of their plates, or frequently bump into objects on their left side. Fortunately, many patients show gradual improvement over time due to the brain’s ability to repair itself and reorganize connections to compensate for lost function. However, the extent of recovery varies across cases and many patients are left with long-term disability. The main goal of this research was to study the brain changes that underlie recovery of attention and gaze toward the ignored side of space. Eye-tracking and brain imaging data were collected before and after a right-sided lesion to part of the frontal cortex in nonhuman primates. Eye movements were recorded to monitor the frequency of looking toward the left versus right visual hemifield, while MRI scans were used to measure the corresponding changes in brain connections during recovery over time. Chapter 2 focused on studying the degree that a lack of left-sided awareness resulted from deficits in attention and/or eye movements. Brain imaging studies in Chapters 3 and 4 demonstrated changes in brain function and structure across frontal-parietal networks in both sides of the brain. We found that patterns of brain reorganization differed based on lesion size and that involvement of brain areas located far from the site of damage was associated with behavioural recovery. This work importantly contributes to the understanding of brain reorganization in visual attention networks and may have implications for treatment and rehabilitation strategies to optimize recovery after brain injury.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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