Neural Substrates of Switching in Parkinson's Disease

  • Disbrow, Elizabeth, (PI)

Project: Research project

Description

The focus of the proposed work is to determine the underlying neural substrates of task switching
deficits in Parkinson's disease (PD) and to link these dysfunctions with behavioral impairments in
everyday life. Although PD was initially considered a motor disorder, deficits in cognitive function
contribute significantly to the hallmark signs of PD. However, there is a lack of consensus
regarding the pathophysiology of these deficits primarily because of the diversity of tasks
previously studied and the challenge of separating the cognitive aspects, such as task switching,
from motor execution. Task switching is the ability to make a change in the plan (switching from
one response option to another, e.g. pressing one button vs. another) and switching can be
externally generated, based on environmental stimuli, or internally or self-generated. We have
chosen to study motor planning, specifically switching, because it is a critical part of normal motor
behavior and is intimately intertwined with the motor deficits associated with PD. Our
HYPOTHESIS is that the planning of these aspects of switching behavior relies on separate basal
ganglia (BG)-thalamocortical circuits that are differentially affected by PD. SPECIFIC AIM 1 is to
test the prediction that PD-related behavioral deficits in internally generated and externally cued
switching are correlated with individual BG-thalamocortical circuits that are differentially affected by
PD. SPECIFIC AIM 2 is to determine if parkinsonian switching deficits and related abnormalities in
BG-thalamocortical activity are correlated with the hallmark signs of PD such as bradykinesia, as
well as impairments in daily activities including verbal fluency and gait initiation. We have
designed a behavioral task that will allow us to dissociate not only motor planning from execution,
but also internally vs. externally generated switching. We will measure patterns of cortical
activation and synchronization with functional magnetic resonance imaging and
magnetoencephalography, respectively, to obtain complimentary anatomic and physiologic views
of switching dysfunctions in PD. Further, we propose to provide a link between the abnormal brain
activity of PD and difficulties in everyday life. SIGNIFICANCE: While cognitive abilities are an
integral part of normal motor behavior, our developing appreciation of cognitive dysfunction in PD
has not yet been incorporated into standard clinical practice. Cognitive symptoms differ among
parkinsonian patients, change over the course of the disease, and may be differentially affected by
dopamine replacement, yet the treatment across patients is similar. Our results can be used to
inform target-specific drug development, direct tailored cognitive neuro-rehabilitation, and evaluate
emerging PD treatment options.
2.
StatusFinished
Effective start/end date7/25/096/30/13

Funding

  • National Institutes of Health: $615,466.00
  • National Institutes of Health: $608,390.00

Fingerprint

Parkinson Disease
Aptitude
Hypokinesia
Neurobehavioral Manifestations
Gait
Rehabilitation
Magnetic Resonance Imaging
Therapeutics
Pharmaceutical Preparations

Keywords

  • Medicine(all)
  • Neuroscience(all)