Mapping and Modulating Brain-Behavior Relationships in Parkinson’s Disease
AuthorLang, Stefan Thomas
Committee MemberKirton, Adam
Kiss, Zelma H. T.
Pike, G. Bruce
transcranial magnetic stimulation
non-invasive brain stimulation
MetadataShow full item record
AbstractWhile Parkinson’s disease (PD) is primarily known as a movement disorder, non-motor symptoms are increasingly recognized as having a significant impact on quality of life. In particular, cognitive impairment and neuropsychiatric symptoms are common and debilitating. These symptoms likely arise from dysfunction in distributed brain networks, which can result from diverse molecular, cellular, and synaptic pathology. Development of effective treatments for these non-motor symptoms will benefit from a detailed understanding of the relationship between the symptomatology and the functional architecture of the brain. These brain networks can be investigated with resting-state functional MRI (rs-fMRI), and can be modulated with non-invasive brain stimulation (NIBS). In the first part of the thesis, using rs-fMRI, we provide novel descriptions of the relationship between cognitive and neuropsychiatric symptoms and functional brain architecture in PD. First, we show that the dysexecutive and posterior cortical profiles of cognitive impairment are related to distinct brain networks. Next, we show that mild behavioral impairment (as a measure of global neuropsychiatric symptoms) is related to altered corticostriatal connectivity. Finally, we develop a novel brain mapping analytical method to investigate the networks underlying the interface of cognitive, neuropsychiatric, and motor symptoms in PD. In the second part of the thesis, we investigate the use of NIBS for cognitive enhancement, both in PD and in healthy subjects. In the first project, subjects with PD and mild cognitive impairment are randomized to receive real or sham intermittent theta-burst transcranial magnetic stimulation of the left dorsolateral prefrontal cortex. Neuropsychological assessments and rs-fMRI are administered before and after the treatment sessions. We show that this treatment paradigm can alter corticostriatal connectivity and may improve executive functioning one-month following stimulation. In the final project, using healthy subjects, we show that it may be possible to improve associative memory performance by targeting theta rhythm high-definition transcranial alternating current stimulation to posterior cortical regions. In sum, this thesis contributes novel descriptions of the relationship between macroscale functional brain networks and the non-motor symptoms of PD, while also describing efforts to modulate these networks using NIBS. This work provides novel targets for neuromodulation, demonstrates the challenges in developing treatments for cognitive impairment, and suggests promising directions for future efforts.
CitationLang, S. T. (2020). Mapping and Modulating Brain-Behavior Relationships in Parkinson’s Disease (Unpublished doctoral thesis). University of Calgary, Calgary, AB.
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