Evaluation of thresholding methods for activation likelihood estimation meta‐analysis via large‐scale simulations

Human Brain Mapping, vol. 43, pp. 3987–3997

Abstract

In recent neuroimaging studies, threshold-free cluster enhancement (TFCE) gained popularity as a sophisticated thresholding method for statistical inference. It was shown to feature higher sensitivity than the frequently used approach of controlling the cluster-level family-wise error (cFWE) and it does not require setting a cluster-forming threshold at voxel level. Here, we examined the applicability of TFCE to a widely used method for coordinate-based neuroimaging meta-analysis, Activation Likelihood Estimation (ALE), by means of large-scale simulations. We created over 200,000 artificial meta-analysis datasets by independently varying the total number of experiments included and the amount of spatial convergence across experiments. Next, we applied ALE to all datasets and compared the performance of TFCE to both voxel-level and cluster-level FWE correction approaches. All three multiple-comparison correction methods yielded valid results, with only about 5% of the significant clusters being based on spurious convergence, which corresponds to the nominal level the methods were controlling for. On average, TFCE's sensitivity was comparable to that of cFWE correction, but it was slightly worse for a subset of parameter combinations, even after TFCE parameter optimization. cFWE yielded the largest significant clusters, closely followed by TFCE, while voxel-level FWE correction yielded substantially smaller clusters, showcasing its high spatial specificity. Given that TFCE does not outperform the standard cFWE correction but is computationally much more expensive, we conclude that employing TFCE for ALE cannot be recommended to the general user.

Authors 7

1. Lennart Frahm corresponding Aachen Department of Psychiatry, Psychotherapy and Psychosomatics School of Medicine

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, School of Medicine RWTH Aachen University Aachen Germany

   Institute of Neuroscience and Medicine (INM7: Brain and Behavior), Research Centre Jülich Jülich Germany

   Department of Psychiatry, Psychotherapy and Psychosomatics, School of Medicine, RWTH Aachen University, Aachen, Germany

2. Edna C. Cieslik

   Forschungszentrum Jülich · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM7: Brain and Behavior), Research Centre Jülich Jülich Germany

   Institute of Systems Neuroscience, Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

3. Felix Hoffstaedter

   Forschungszentrum Jülich · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM7: Brain and Behavior), Research Centre Jülich Jülich Germany

   Institute of Systems Neuroscience, Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

4. Theodore Daniel Satterthwaite

   University of Pennsylvania

   Affiliation as printed

   Department of Psychiatry, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

   Penn Lifespan Informatics and Neuroimaging Center, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

   Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

   Penn Lifespan Informatics and Neuroimaging Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

5. Peter T. Fox

   The University of Texas at San Antonio Health Science Center

   Affiliation as printed

   Research Imaging Institute University of Texas Health Science Center San Antonio Texas USA

   Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas, USA

6. Robert Langner

   Forschungszentrum Jülich · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM7: Brain and Behavior), Research Centre Jülich Jülich Germany

   Institute of Systems Neuroscience, Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

7. Simon Bodo Eickhoff

   Forschungszentrum Jülich · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM7: Brain and Behavior), Research Centre Jülich Jülich Germany

   Institute of Systems Neuroscience, Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany