Type
Text
Type
Dissertation
Advisor
Luhmann, Christian | Leung, Hoi-Chung | Canli, Turhan | Li, Chiang-shan R.
Date
2016-12-01
Keywords
basal ganglia, dopamine, fMRI, levodopa, proactive control, response inhibition | Neurosciences -- Cognitive psychology -- Psychobiology
Department
Department of Biopsychology
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77006
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. The hallmark motor symptoms of the disease, such as tremor and rigidity, are generally well-treated with medications that boost the neurotransmitter dopamine. However, whether dopamine-replacement therapy restores cognitive function is under intense debate. While some studies have shown cognitive benefits for individuals taking dopaminergic medications, others have reported null findings or even exacerbated cognitive impairment for individuals in the medicated state. Current theories generally attribute the variety of findings to task differences and the uneven pattern of PD neuropathology across the basal ganglia. However, few studies consider how disease duration may interact with medication status to produce changes in cognitive function. This is an important consideration, as profound loss of dopamine-containing cells in the advanced stages of PD renders dopaminergic medication relatively ineffective. Here, in a meta-analysis it is evident that disease duration modulates cognitive function for individuals on dopaminergic medication. In a functional magnetic resonance imaging study of the stop-signal task (SST), we find that early-stage individuals have a restoration of response inhibition behavior with dopaminergic medication, in contrast to previous studies reporting null effects in more advanced individuals with PD. Bayesian computational modeling of SST performance identified a possible mechanism by which dopaminergic medication improves response inhibition in early-stage PD. Specifically, compared to a 12-hour washout “off’ medication state, individuals in the “on†state showed improvements in their ability to make behavioral adjustments across trials of the task. This manifested itself in increased brain activations to the anticipation of salient events, and decreased activations to surprise in lateral and medial frontoparietal regions. Together, these findings highlight the importance of disease duration when considering medication effects on cognitive function in PD. They also identify a potential novel mechanism by which dopamine supports frontoparietal cognitive control, centered on trial-to-trial learning, behavioral adjustment and increased neural signatures of anticipation. | 86 pages
Recommended Citation
Manza, Pete, "Neurocomputation, dopaminergic treatment, and cognitive control in early-stage Parkinson's Disease" (2016). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2868.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2868