This is a continuing proposal to address a variety of biostatistical problems motivated by current issues in imaging neuroscience, as during the previous funding cycle.
New aims : the development of flexible semiparametric growth curve models for accelerated longitudinal designs; advancing methodology for replicated spatial point processes and 3-D brain brain cell assemblies; and new methods and algorithms for semiautomatic identification of human brain cells. We propose to generalize our proposed individual low-rank smooth regression methods to compositional data via a Iogit-Gaussian model within a hierarchical Bayes framework. We seek to produce practical guidelines for designing cost-effective longitudinal studies involving expensive outcomes measurements. We propose to advance Poisson random field methods for sparse processes, motivated by the multiple cell types and regional structures in the human brain. Empirical data analysis will continue to play a central role in the proposed research. Our human brain mapping research by magnetic resonance imaging (MRI) and positron emission tomography (PET) and human brain tissue microscopy again relates directly to the study of psychiatric and neurological outcomes in healthy and ill subjects, both young and old. Through our collaborating biostatistical and neuroscience institutions, our ongoing translational research develops and links modem biostatistical methods with complementary work in longitudinal anatomic human brain imaging, functional human brain imaging and human brain tissue microscopy. Brain diseases addressed are schizophrenia, bipolar disorder and Parkinson's disease. However, potential applications of our methods go well beyond human brain mapping to include longitudinal and spatial epidemiology, risk assessment, health policy and management, nutrition, and other fields in which cost and feasibility constraints impose restrictions on the numbers of subjects studied and on the numbers and timings of their repeated measurements.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS037483-06A1
Application #
6822365
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Gilbert, Peter R
Project Start
1998-04-01
Project End
2007-05-31
Budget Start
2004-09-01
Budget End
2005-05-31
Support Year
6
Fiscal Year
2004
Total Cost
$260,619
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Cataldo, Anne M; McPhie, Donna L; Lange, Nicholas T et al. (2010) Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol 177:575-85
Lange, Nicholas; Dubray, Molly B; Lee, Jee Eun et al. (2010) Atypical diffusion tensor hemispheric asymmetry in autism. Autism Res 3:350-8
Anderson, J S; Lange, N; Froehlich, A et al. (2010) Decreased left posterior insular activity during auditory language in autism. AJNR Am J Neuroradiol 31:131-9
Forester, Brent P; Berlow, Yosef A; Harper, David G et al. (2010) Age-related changes in brain energetics and phospholipid metabolism. NMR Biomed 23:242-50
Basu, A C; Tsai, G E; Ma, C-L et al. (2009) Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Mol Psychiatry 14:719-27
Sheth, Archana; Berretta, Sabina; Lange, Nicholas et al. (2008) The amygdala modulates neuronal activation in the hippocampus in response to spatial novelty. Hippocampus 18:169-81
Berretta, Sabina; Pantazopoulos, Harry; Lange, Nicholas (2007) Neuron numbers and volume of the amygdala in subjects diagnosed with bipolar disorder or schizophrenia. Biol Psychiatry 62:884-93
Pantazopoulos, Harry; Lange, Nicholas; Baldessarini, Ross J et al. (2007) Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia. Biol Psychiatry 61:640-52
Frazier, Jean A; Chiu, Sufen; Breeze, Janis L et al. (2005) Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Am J Psychiatry 162:1256-65
Harezlak, Jaroslaw; Ryan, Louise M; Giedd, Jay N et al. (2005) Individual and population penalized regression splines for accelerated longitudinal designs. Biometrics 61:1037-48

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