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Thomas Nichols

Publications and source records attributed to Thomas Nichols.

6 recordsLinked to original sources

Lesion probability maps of white matter hyperintensities in elderly individuals: results of the Austrian stroke prevention study.

OBJECTIVE: White matter hyperintensities (WMH) are common on brain MRI of the elderly. Their size ranges from punctate to early confluent to confluent lesions. While this increase in extension is frequently seen as evidence for a continuum of changes, histological data and clinical follow-up suggest differences in underlying pathology and their progression. METHODS: We tested this hypothesis by exploring the distributions of punctuate and confluent lesions using lesion probability maps (LPM) generated from MRI scans of 189 participants (mean age 60.8+/-6.2 years) in the Austrian Stroke Prevention Study. We dichotomised WMH according to the classification by Fazekas et al. [punctate (n=143) vs. early confluent and confluent (n=33)] to run voxel-based t-tests using permutation-based nonparametric inference. To test alternative hypotheses, we created similar LPM for age and arterial hypertension. RESULTS: We observed significant differences in the spatial distribution of lesions for the two WMH groups (p<0.01). Punctate lesions were more diffusely distributed throughout the cerebral white matter (peak probability approximately 5%) relative to confluent lesions (peak probability 45%). Confluent lesions had greatest likelihood of being found in perfusion "watershed" regions. These differences in distribution could not be explained by differences in age or hypertension only, as both greater age and the diagnosis of hypertension were associated with WMH abutting the occipital horns. CONCLUSIONS: Punctate and early confluent to confluent WMH show distinguishable differences in their spatial distribution within a normal elderly population. The pattern of punctate WMH is probably a consequence of mixed etiologies. Preferential localization of the more confluent WMH with arterial watershed areas implies a stronger ischemic component in their development.

Age Factors↗

Valid conjunction inference with the minimum statistic.

In logic a conjunction is defined as an AND between truth statements. In neuroimaging, investigators may look for brain areas activated by task A AND by task B, or a conjunction of tasks (Price, C.J., Friston, K.J., 1997. Cognitive conjunction: a new approach to brain activation experiments. NeuroImage 5, 261-270). Friston et al. (Friston, K., Holmes, A., Price, C., Buchel, C., Worsley, K., 1999. Multisubject fMRI studies and conjunction analyses. NeuroImage 10, 85-396) introduced a minimum statistic test for conjunction. We refer to this method as the minimum statistic compared to the global null (MS/GN). The MS/GN is implemented in SPM2 and SPM99 software, and has been widely used as a test of conjunction. However, we assert that it does not have the correct null hypothesis for a test of logical AND, and further, this has led to confusion in the neuroimaging community. In this paper, we define a conjunction and explain the problem with the MS/GN test as a conjunction method. We present a survey of recent practice in neuroimaging which reveals that the MS/GN test is very often misinterpreted as evidence of a logical AND. We show that a correct test for a logical AND requires that all the comparisons in the conjunction are individually significant. This result holds even if the comparisons are not independent. We suggest that the revised test proposed here is the appropriate means for conjunction inference in neuroimaging.

Arousal↗

Controlling the familywise error rate in functional neuroimaging: a comparative review.

Functional neuroimaging data embodies a massive multiple testing problem, where 100,000 correlated test statistics must be assessed. The familywise error rate, the chance of any false positives is the standard measure of Type I errors in multiple testing. In this paper we review and evaluate three approaches to thresholding images of test statistics: Bonferroni, random field and the permutation test. Owing to recent developments, improved Bonferroni procedures, such as Hochberg's methods, are now applicable to dependent data. Continuous random field methods use the smoothness of the image to adapt to the severity of the multiple testing problem. Also, increased computing power has made both permutation and bootstrap methods applicable to functional neuroimaging. We evaluate these approaches on t images using simulations and a collection of real datasets. We find that Bonferroni-related tests offer little improvement over Bonferroni, while the permutation method offers substantial improvement over the random field method for low smoothness and low degrees of freedom. We also show the limitations of trying to find an equivalent number of independent tests for an image of correlated test statistics.

Brain↗

Thresholding of statistical maps in functional neuroimaging using the false discovery rate.

Finding objective and effective thresholds for voxelwise statistics derived from neuroimaging data has been a long-standing problem. With at least one test performed for every voxel in an image, some correction of the thresholds is needed to control the error rates, but standard procedures for multiple hypothesis testing (e.g., Bonferroni) tend to not be sensitive enough to be useful in this context. This paper introduces to the neuroscience literature statistical procedures for controlling the false discovery rate (FDR). Recent theoretical work in statistics suggests that FDR-controlling procedures will be effective for the analysis of neuroimaging data. These procedures operate simultaneously on all voxelwise test statistics to determine which tests should be considered statistically significant. The innovation of the procedures is that they control the expected proportion of the rejected hypotheses that are falsely rejected. We demonstrate this approach using both simulations and functional magnetic resonance imaging data from two simple experiments.

Adult↗

Trends in fluoroquinolone (ciprofloxacin) resistance in enterobacteriaceae from bacteremias, England and Wales, 1990-1999.

The Public Health Laboratory Service receives antibiotic susceptibility data for bacteria from bloodstream infections from most hospitals in England and Wales. These data were used to ascertain resistance trends to ciprofloxacin from 1990 through 1999 for the most prevalent gram-negative agents: Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus mirabilis. Significant increases in resistance were observed for all four species groups. For E. coli, ciprofloxacin resistance rose from 0.8% in 1990 to 3.7% in 1999 and became widely scattered among reporting hospitals. The prevalence of resistance in Klebsiella spp. rose from 3.5% in 1990, to 9.5% in 1996 and 7.1% in 1999, while that in Enterobacter spp. rose from 2.1% in 1990 to 10.5% in 1996 and 10.9% in 1999. For both Klebsiella and Enterobacter spp., most resistance was localized in a few centers. Resistance was infrequent and scattered in P. mirabilis, but reached a prevalence of 3.3% in 1999.

Bacteremia↗