Functional and Structural Brain Reorganization After Unilateral Prefrontal Cortex Lesions In Macaques
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.