The proposed research career award is designed to develop the candidate's clinical research skills in order to prepare him for a career as an independent investigator in the application of functional brain imaging methods to the field of experimental therapeutics for neurodegenerative diseases. Research plan: Parkinson's disease (PD) and Huntington's disease (HD) may be viewed respectively as prototypic examples of degenerative hypokinetic and hyperkinetic movement disorders. Great strides have been made in the-understanding of the pathophysiological mechanisms underlying the neurodegenerative processes in both PD and HD, prompting clinical trials of new therapies aimed at slowing or halting the progression of these diseases. To assess these new therapies, reliable in vivo markers of neuronal loss are needed. Currently available clinical and functional measures of disease progression are relatively insensitive, and may not accurately reflect the extent of neuropathological change. Alternatively, quantitative biologically relevant brain imaging markers now exist which may be suitable as outcome measures for clinical trials. The goal of the proposed project is to assess the extent to which neurochemical and metabolic positron emission tomography (PET) imaging markers are sensitive to change in PD and HD, and to compare these measures to standard clinical indices of disease progression. We hypothesize that PET measures will be more sensitive to disease progression than clinical measures. If this is the case, clinical trials designed to assess potential neuroprotective therapies could require fewer patients and be completed in less time. Educational plan: By completing this project the candidate will gain extensive practical experience in functional brain imaging. In addition, the educational plan will focus on six main objectives: 1) The learning of PET imaging techniques; 2) The development of skills in brain network analysis and modeling; 3) The advancement of the candidate's knowledge of statistical methods; 4) The learning of the principals of functional magnetic resonance imaging (fMRI); 5) The development of the applicant's skills in laboratory management and supervision; and 6) The preparation of manuscripts and scientific presentations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS002011-03
Application #
6187036
Study Section
NST-2 Subcommittee (NST)
Program Officer
Sheehy, Paul A
Project Start
1998-07-01
Project End
2001-12-14
Budget Start
2000-07-01
Budget End
2001-12-14
Support Year
3
Fiscal Year
2000
Total Cost
$120,879
Indirect Cost
Name
North Shore University Hospital
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Feigin, A; Tang, C; Ma, Y et al. (2007) Thalamic metabolism and symptom onset in preclinical Huntington's disease. Brain 130:2858-67
Zgaljardic, Dennis J; Borod, Joan C; Foldi, Nancy S et al. (2007) Relationship between self-reported apathy and executive dysfunction in nondemented patients with Parkinson disease. Cogn Behav Neurol 20:184-92
Zgaljardic, Dennis J; Borod, Joan C; Foldi, Nancy S et al. (2006) An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease. J Clin Exp Neuropsychol 28:1127-44
Billingsley-Marshall, Rebecca L; Simos, Panagiotis G; Papanicolaou, Andrew C (2004) Reliability and validity of functional neuroimaging techniques for identifying language-critical areas in children and adults. Dev Neuropsychol 26:541-63
Feigin, A; Ghilardi, M F; Carbon, M et al. (2003) Effects of levodopa on motor sequence learning in Parkinson's disease. Neurology 60:1744-9
Carbon, Maren; Ghilardi, Maria Felice; Feigin, Andrew et al. (2003) Learning networks in health and Parkinson's disease: reproducibility and treatment effects. Hum Brain Mapp 19:197-211
Mentis, Marc J; McIntosh, Anthony R; Perrine, Kenneth et al. (2002) Relationships among the metabolic patterns that correlate with mnemonic, visuospatial, and mood symptoms in Parkinson's disease. Am J Psychiatry 159:746-54
Feigin, Andrew; Antonini, Angelo; Fukuda, Masafumi et al. (2002) Tc-99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism. Mov Disord 17:1265-70
Feigin, A; Ghilardi, M F; Fukuda, M et al. (2002) Effects of levodopa infusion on motor activation responses in Parkinson's disease. Neurology 59:220-6
Feigin, A; Leenders, K L; Moeller, J R et al. (2001) Metabolic network abnormalities in early Huntington's disease: an [(18)F]FDG PET study. J Nucl Med 42:1591-5

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