Memory impairment is a common problem in Parkinson' disease (PD). This proposal investigates working memory (i.e. short-term memory) deficits in PD patients as compared to normal elderly.
My first aim i s to determine the nature of the working memory deficits in PD. 1 hypothesize an impairment in a specific component of working memory called the """"""""central executive system"""""""" (CBS), that is critical for allocating limited attentional resources. This hypothesis will be tested by performing dual- task paradigms designed to directly examine CBS functioning. An alternative hypothesis, that PD patients have weakened working memory representations rather than a defective CBS, will also be tested.
The second aim i s to define the neuroanatomical basis of working memory. Primate studies have shown that the caudal principal sulcus is critical for working memory. Physiological studies have not examined the CBS of working memory in either primates or humans. Cognitive activation studies during dual-task paradigms using PET and functional MRI will be performed in normal human subjects to define the neural network subserving the CBS of working memory. I hypothesize that the dorsolateral prefrontal cortex (Brodmann areas 9 and 46) will activate during dual-task paradigms. I will also examine PD patients with CBS deficits. I hypothesize that CBS impairments found """"""""off-line"""""""" in PD patients will correlate with resting hypoperfusion in the dorsolateral prefrontal cortex. Also, these patients will fail to activate the dorsolateral prefrontal cortex when performing these CBS tasks, suggesting that this region is functionally defective in this disease.
The third aim i s to determine the neurochemical basis of working memory. The role of dopamine in human working memory will be tested by studying PD patients """"""""on"""""""" and """"""""off' medications and investigating the effect of administering a dopaminergic agonist to normal elderly subjects. I hypothesize that the CBS of working memory will improve during the """"""""on"""""""" state in PD patients and after dopamine stimulation in normal elderly subjects. In this fashion, a multi-factorial model characterizing the cognitive, neuroanatomical and neurochemical basis for working memory will be defined. These studies will improve our knowledge of working memory and provide a rational basis for diagnostic and therapeutic intervention in patients with working memory impairments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001762-04
Application #
2714375
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Tom P
Project Start
1995-06-01
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Postle, Bradley R; Awh, Edward; Serences, John T et al. (2013) The positional-specificity effect reveals a passive-trace contribution to visual short-term memory. PLoS One 8:e83483
Postle, Bradley R; Desposito, Mark; Corkin, Suzanne (2005) Effects of verbal and nonverbal interference on spatial and object visual working memory. Mem Cognit 33:203-12
Postle, B R; Awh, E; Jonides, J et al. (2004) The where and how of attention-based rehearsal in spatial working memory. Brain Res Cogn Brain Res 20:194-205
Postle, Bradley R; Druzgal, T Jason; D'Esposito, Mark (2003) Seeking the neural substrates of visual working memory storage. Cortex 39:927-46
Postle, Bradley R; D'Esposito, Mark (2003) Spatial working memory activity of the caudate nucleus is sensitive to frame of reference. Cogn Affect Behav Neurosci 3:133-44
Druzgal, T J; D'Esposito, M (2001) A neural network reflecting decisions about human faces. Neuron 32:947-55
Postle, B R; Berger, J S; Goldstein, J H et al. (2001) Behavioral and neurophysiological correlates of episodic coding, proactive interference, and list length effects in a running span verbal working memory task. Cogn Affect Behav Neurosci 1:10-21
Druzgal, T J; D'Esposito, M (2001) Activity in fusiform face area modulated as a function of working memory load. Brain Res Cogn Brain Res 10:355-64
Rypma, B; D'Esposito, M (2000) Isolating the neural mechanisms of age-related changes in human working memory. Nat Neurosci 3:509-15
D'Esposito, M; Postle, B R; Rypma, B (2000) Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies. Exp Brain Res 133:11-Mar

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