The neurological diseases of aging lack reliable clinical markers in the physical and mental status examination. Differential diagnosis between normal aging and early senile dementia of the Alzheimer type (SDAT), between dementia and pseudodementia and between SDAT and multi-infarct dementia is problematic. The development of clinical criteria depends on a better understanding of brain function and of functional response to damage. Theories of higher cortical function, derived from studies of stroke, are dependent on localization of function and are thus not applicable to the diffuse diseases of aging. Connectionism is a method of neurologic modeling that uses distributed representations and parallel processing. These models are physiological in that they use several brain-like skills: learning, ability to generalize, disambiguation of inputs, retrieval of memory by content not location, and graceful degradation. The goal will be to use neural network models to adduce clinical markers for specific diseases and for prediction and testing of potential neurotransmitter therapies. These models will focus clinical trials by correlating neurotransmitter effects with clinical findings. A proposal is presented for a training program in connectionism oriented to basic research in the clinical neurology of aging. Phase I of the program will involve course work in biophysics, computer science, statistics and mathematics as well as laboratory exposure in neurophysiology, clinical work in dementia and experience with ongoing connectionist research in Dr. Sejnowski's laboratory. In phase II, connectionist methods will be used to design systems that reflect the specific diseases of aging. Clinical and neurophysiological data will be used to constrain the models. The design is expected to use diffuse associative connectivity with specific synaptic connectivity added. These models will be manipulated to simulate particular diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Physician Scientist Award (K11)
Project #
5K11AG000382-04
Application #
3084909
Study Section
Aging Review Committee (AGE)
Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Lytton, W W; Sejnowski, T J (1992) Computer model of ethosuximide's effect on a thalamic neuron. Ann Neurol 32:131-9
Lytton, W W (1991) Simulations of a phase comparing neuron of the electric fish Eigenmannia. J Comp Physiol A 169:117-25
Lytton, W W; Kristan, W B (1989) Localization of a leech inhibitory synapse by photo-ablation of individual dendrites. Brain Res 504:43-8