COMPUTATIONAL MODELING AND SIMULATION AS ENABLERS FOR BIOLOGICAL DISCOVERY 187
least constrained, are least understood, and have the greatest impact on synaptic function. Specifically,
the results clearly demonstrate that synaptic geometry, receptor distribution, and vesicle release loca-
tion each have a profound quantitative impact on the efficacy of the postsynaptic response. This means
that attention to accuracy in the model-building process must be a prime concern.
5.4.5.5 Neuropsychiatry^106
The field of computational neuropsychiatry has been exploding with applications of large-deforma-
tion brain mapping technology that provide mechanisms for discovering neuropsychiatric disorders of
many types. The hippocampus is a region of the brain (depicted in green in Figure 5.19) that has been
implicated in schizophrenia and other neurodegenerative diseases such as Alzheimer’s. Using large-
deformation brain mapping tools in computational anatomy, researchers can define, visualize, and
measure the volume and shape of the hippocampus. These methods allow for precise assessment of
changes in hippocampal formation.
Researchers at the Center for Imaging Science (CIS) used mapping tools to compare the left and
right hippocampi (Figure 5.20) in 15 pairs of schizophrenic and control subjects. In the schizophrenic
FIGURE 5.19 The hippocampus in situ. SOURCE: Courtesy of Michael Miller, Johns Hopkins University.
(^106) Section 5.4.5.5 is based on L. Wang, S.C. Joshi, M.I. Miller, and J.G. Csernansky, “Statistical Analysis of Hippocampal
Asymmetry in Schizophrenia,” Neuroimage 14(3):531-545, 2001; J.G. Csernansky, L. Wang, S. Joshi, J.P. Miller, M. Gado, D. Kido,
D. McKeel, et al., “Early DAT Is Distinguished from Aging by High-dimensional Mapping of the Hippocampus,” Neurology
55(11):1636-1643, 2000.