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Abstract:
False discovery rate (FDR) control has become a standard technique in
neuroimaging. Recent work has shown that a finer grained estimate of the FDR is
obtained by estimating, at a specific value of the test statistic, the scaled
ratio of the null density to the observed density of the test statistic. The
method can be extended by allowing an external covariate, also measured on the
points where the hypothesis was tested, to modulate estimation of this local
FDR. The current work, in addition to demonstrating these methods by
re-analyzing results from two previously published investigations of cortical
thickness, presents a method to test if the covariate modulation differs
significantly from chance. The first study compared schizophrenia patients to
healthy controls and the second compared genotypes of the -633 T/A polymorphism
of the gene coding the brain derived neurotrophic factor (BDNF) protein in a
subset of the subjects from the case/control study. Local FDR estimates
increased findings over FDR in both studies. Using p-values from the
case/control study to modulate local FDR estimation in the BDNF study further
increased findings. The relationship between case/control related and BDNF
related cortical thickness variation was found to be highly significant,
providing support for this gene's involvement in the etiology of the disease.
The increased statistical precision from more accurate models of the
distribution of the test statistic demonstrates the potential of these methods
for neuroimaging and suggests the possibility to test novel hypothesis.
