Parkinson's disease (PD) is among the most common forms of neurodegenerative disease in older adults. PD is associated with progressive loss of dopamine-producing neurons of the basal ganglia, which in turn disrupts normal basal ganglia activity and produces well-known movement abnormalities (e.g., bradykinesia, tremor). Of increasing concern are the effects of PD and its treatment on specific cognitive processes. Several contemporary neurocognitive models suggest that frontal-basal ganglia circuits play a central role in executive cognitive control. In our constantly changing environments, one particularly important aspect of executive control supported by this circuitry is the inhibition of behavior. Preliminary behavioral data for this application show that PD patients are less effective at inhibiting responses than healthy controls across several experimental paradigms. This data supports the central hypothesis behind this project that PD compromises the neurocognitive control system that is responsible for the inhibition of behavior.
Specific aims provide additional empirical tests of this hypothesis by linking the response inhibition deficits in PD to underlying neurophysiological mechanisms and determining the effects of treatments (dopamine medication, subthalamic nucleus deep brain stimulation) for PD on behavioral and neurophysiological measures of inhibition. Career development training focuses on the acquisition of expertise in event-related brain potential (ERP) and electromyography (EMG) recordings that can be used to track the activation of an incorrect response and the inhibition of this response with millisecond precision as these processes unfold over the course of a mental reaction. Career development training and support is enhanced by local and outside collaborations that provide expert backgrounds in the neuroscience of cognitive control, the diagnosis and treatment of Parkinson's disease, and clinical neurophysiology. Cognitive deficits that accompany PD produce significant declines in quality of life and functional independence. A better understanding of these deficits and their neurophysiological mechanisms can lead to better treatments.

Public Health Relevance

Parkinson's disease is among the most common forms of neurodegenerative disease in older adults. Cognitive deficits that accompany Parkinson's disease produce significant declines in quality of life and functional independence. The training and proposed studies outlined in this application combine psychophysiological and behavioral measures to investigate the effects of PD and its treatment on the cognitive control system responsible for the inhibition of behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23AG028750-04
Application #
8399120
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Wagster, Molly V
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2012-02-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$158,166
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Neurology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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van den Wildenberg, Wery P M; Ridderinkhof, K Richard; van Wouwe, Nelleke C et al. (2017) Overriding actions in Parkinson's disease: Impaired stopping and changing of motor responses. Behav Neurosci 131:372-84
van Wouwe, N C; Pallavaram, S; Phibbs, F T et al. (2017) Focused stimulation of dorsal subthalamic nucleus improves reactive inhibitory control of action impulses. Neuropsychologia 99:37-47
Slagter, H A; van Wouwe, N C; Kanoff, K et al. (2016) Dopamine and temporal attention: An attentional blink study in Parkinson's disease patients on and off medication. Neuropsychologia 91:407-414
van Wouwe, Nelleke C; Kanoff, Kristen E; Claassen, Daniel O et al. (2016) Dissociable Effects of Dopamine on the Initial Capture and the Reactive Inhibition of Impulsive Actions in Parkinson's Disease. J Cogn Neurosci 28:710-23
van Wouwe, Nelleke C; Kanoff, Kristen E; Claassen, Daniel O et al. (2016) The Allure of High-Risk Rewards in Huntington's disease. J Int Neuropsychol Soc 22:426-35
van Wouwe, N C; van den Wildenberg, W P M; Ridderinkhof, K R et al. (2015) Easy to learn, hard to suppress: The impact of learned stimulus-outcome associations on subsequent action control. Brain Cogn 101:17-34
Tramontana, Michael G; Molinari, Anna L; Konrad, Peter E et al. (2015) Neuropsychological effects of deep brain stimulation in subjects with early stage Parkinson's disease in a randomized clinical trial. J Parkinsons Dis 5:151-63
Claassen, Daniel O; van den Wildenberg, Wery P M; Harrison, Madaline B et al. (2015) Proficient motor impulse control in Parkinson disease patients with impulsive and compulsive behaviors. Pharmacol Biochem Behav 129:19-25
Bissett, Patrick G; Logan, Gordon D; van Wouwe, Nelleke C et al. (2015) Generalized motor inhibitory deficit in Parkinson's disease patients who freeze. J Neural Transm (Vienna) 122:1693-701

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