SDM reference manual

Introduction

Signed Differential Mapping or SDM is a statistical technique for meta-analyzing studies on differences in brain activity or structure which used neuroimaging techniques such as fMRI, VBM or PET. It may also refer to a specific piece of software created by the SDM Project to carry out such meta-analyses.

Overview of the method

SDM adopted and combined various positive features from previous methods, such as Activation Likelihood Estimate (ALE) or Multilevel Kernel Density Analysis (MKDA), and introduced a series of improvements and novel features. One of the new features, introduced to avoid positive and negative findings in the same voxel as seen in previous methods, was the representation of both positive differences and negative differences in the same map, thus obtaining a signed differential map (SDM).

The method has three steps. First, studies and coordinates of cluster peaks (e.g. the voxels were the differences between patients and healthy controls were highest) are selected according to SDM inclusion criteria. Second, these coordinates are used to create an SDM map for each study. Finally, study maps are meta-analyzed using several different tests to complement the main outcome with sensitivity and heterogeneity analyses.

Inclusion criteria

It is not uncommon in neuroimaging studies that some regions (e.g. a priori regions of interest) are more liberally thresholded than the rest of the brain. However, a meta-analysis of studies with such regional differences in thresholds would be biased towards these regions, as they are more likely to be reported just because authors apply more liberal thresholds in them. In order to overcome this issue SDM introduced a criterion in the selection of the coordinates, which can be summarized as:

" ONLY include those RESULTS which were statistically significant at the WHOLE-BRAIN level and using the SAME THRESHOLD "

Another criterion introduced by SDM is the preference for results that are corrected for multiple comparisons, as far as they provide some information (i.e. at least one statistically significant coordinate).

Pre-processing of studies

After conversion of coordinates to Talairach space, an SDM map is created for each study. This consists in recreating the clusters of difference by means of an un-normalized Gaussian Kernel, so that voxels closer to the peak coordinate have higher values. A rather large full-width at half-maximum (FWHM) of 25mm is used to account for different sources of spatial error, e.g. coregistration mismatch in the studies, the size of the cluster or the location of the peak within the cluster. Within a study, values obtained by close Gaussian kernels are summed, though values are limited to [-1,1] to avoid a bias towards studies reporting various coordinates in close proximity, as voxels can achieve rather large values.

Statistical comparisons

SDM provides several different statistical analyses in order to complement the main outcome with sensitivity and heterogeneity analyses.

- The main statistical analysis is the mean analysis, which consists in calculating the mean of the voxel values in the different studies. This mean is weighted by the sample size so that studies with large sample sizes contribute more.

- The descriptive analysis of quartiles describes the weighted proportion of studies with strictly positive (or negative) values in a voxel, thus providing a p-value-free measure of the effect size.

- Subgroup analyses are mean analyses applied to groups of studies to allow the study of heterogeneity.

- Linear model analyses (e.g. meta-regression) are a generalization of the mean analysis to allow comparisons between groups and the study of possible confounds. It must be noted that a low variability of the regressor is critical in meta-regressions, so they are recommended to be understood as exploratory and to be more conservatively thresholded (e.g. a threshold of 0.0001 or 0.0002 has been proposed).

- Jack-knife analysis consists in repeating a test as many times as studies have been incl, discarding one different study each time, i.e. removing one study and repeating the analyses, then putting that study back and removing another study and repeating the analysis, and so on. The idea is that if a significant brain region remains significant in all or most of the combinations of studies it can be concluded that this finding is highly replicable.

The statistical significance of the analyses is checked by standard randomization tests. It is recommended to use uncorrected p-values = 0.001, as this significance has been found in this method to be approximately equivalent to a corrected p-value = 0.05. A false discovery rate (FDR) = 0.05 has been found in this method to be too conservative. Values in a Talairach label or coordinate can also be extracted for further processing or graphical presentation.

SDM software

SDM is software written by the SDM project to aid the meta-analysis of voxel-based neuroimaging data. It is distributed as freeware including both a command-line and a graphical interface.

The authors | IoP King's College London | NeuroImageN