Reliability of PET activation across statistical methods, subject groups, and sample sizes

Abstract

Four pixel-based methods for estimating regional activation in positron emission tomography (PET) images were implemented so as to allow the comparison of their performances in the same dataset. Change distribution analysis, Worsley's method, a pixelwise general linear model, a nonparametric method, and several methods derived from them were investigated. Important technical factors, including the degree of smoothing, stereotactic transform, coregistration algorithm, search volume, and the volumetric alpha level, were held constant. The dataset, which was obtained with a verb generation paradigm, was large enough to permit assessment of concordance between independent samples of conventional size, as well assessment of within-cohort replicability. (Eighteen normal subjects performed four GENERATE-READ pairs each.) Same-task (noise) images were also analyzed.In noise datasets, type I errors (false positives) occurred at the nominal rate (in 5% of datasets). Detected regions of activation were highly likely to be internally replicated (93%). The detected activations were a superset of activations previously reported using the same paradigm. The methods were chiefly distinguished by type 11 error rates and by the stability of the location of activation clusters. Those methods dependent on local variance estimates were less powerful with small sample sizes and less stable with respect to the attributed location of task-induced changes. The use of pooled variance (Worsley's method) reduced these problems, but variance was not stationary. Overall, the power of all analyses was modest with samples of conventional size (nine subjects x one or two task-pairs). Modeling of the sources of variance, particularly improvement of anatomical standardization, is likely to improve the power of pixel-based analyses.have been applied to numerous problems in cognitive neuroscience over the last decade. Progress in functional neuroimaging was greatly accelerated by the advent of computerized image analysis, especially the application of "pixel-based' methods of statistical analysis to activation images generated by positron emission tomography (PET). These methods, in which the fundamental unit of analysis is the pixel (picture element) rather than a region of intercst (ROI), were attractive because they did not require a priori anatomi-0 1996 Wiley-Liss, Inc.

Phonology, semantics, and the role of the left inferior prefrontal cortex

“…Specifically, posterior temporal and fusiform activation has been found for other word and object naming tasks [Bookheimer et al, 1995;Howard et al, 1992;Vandenberghe et al, 1996], as well as more complex task conditions. For instance, posterior temporal activation during the verb generation has been reported Grabowski et al, 1996;Warburton et al, 1996], and greater activation in an inferior temporal/ fusiform region was found when subjects judged whether adjective-noun word pairs met a particular semantic constraint (small animals with ''positive'' attributes), than when they judged whether multi-r Fiez r r 80 r syllabic nonwords contained a particular phoneme sequence (/b/ preceded by /d/) [Demonet et al, 1992].…”

Activation pattern reproducibility: Measuring the effects of group size and data analysis models

“…A central problem in brain activation experiments is the reproducibility of the resulting functional activation patterns. To date this issue has been addressed only for spatially localized suprathreshold foci [e.g., Grabowski et al, 1996]. Moreover, comparison of activation patterns using the ''corner-cube environ-ment'' [Schaper et al, 1996] or ''functional volumes models'' [Fox et al, 1996], which provide a symbolic representation of activated foci, typically summarize only spatial information for suprathreshold signals.…”

Peer Review #2 of "We need to talk about reliability: making better use of test-retest studies for study design and interpretation (v0.2)"

“…Many previous articles on statistical power have thus used repeatability of effects as a criterion for determining the sample size instead of actual power analysis. There are various articles that deal with power in voxel-based functional neuroimaging (Grabowski et al, 1996;Andreasen et al, 1996;Van Horn et al, 1998;Petersson et al, 1999;Desmond and Glover, 2002), but all of them concern activation studies, not PET neuroreceptor studies.…”