Cortical surface-based threshold-free cluster enhancement and cortexwise mediation.
Threshold-free cluster enhancement (TFCE) is a sensitive means to incorporate spatial neighborhood information in neuroimaging studies without using arbitrary thresholds. The majority of methods have applied TFCE to voxelwise data. The need to understand the relationship among multiple variables and imaging modalities has become critical. We propose a new method of applying TFCE to vertexwise statistical images as well as cortexwise (either voxel- or vertexwise) mediation analysis. Here we present TFCE_mediation, a toolbox that can be used for cortexwise multiple regression analysis with TFCE, and additionally cortexwise mediation using TFCE. The toolbox is open source and publicly available (https://github.com/trislett/TFCE_mediation). We validated TFCE_mediation in healthy controls from two independent multimodal neuroimaging samples (N = 199 and N = 183). We found a consistent structure-function relationship between surface area and the first independent component (IC1) of the N-back task, that white matter fractional anisotropy is strongly associated with IC1 N-back, and that our voxel-based results are essentially identical to FSL randomise using TFCE (all PFWE<0.05). Using cortexwise mediation, we showed that the relationship between white matter FA and IC1 N-back is mediated by surface area in the right superior frontal cortex (PFWE< 0.05). We also demonstrated that the same mediation model is present using vertexwise mediation (PFWE< 0.05). In conclusion, cortexwise analysis with TFCE provides an effective analysis of multimodal neuroimaging data. Furthermore, cortexwise mediation analysis may identify or explain a mechanism that underlies an observed relationship among a predictor, intermediary, and dependent variables in which one of these variables is assessed at a whole-brain scale. Hum Brain Mapp 38:2795-2807, 2017. © 2017 Wiley Periodicals, Inc.
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Tristram A
TA
Lett
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Lea
L
Waller
Department of Psychiatry, University of Heidelberg, Heidelberg, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Heike
H
Tost
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Ilya M
IM
Veer
Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Canada.
Arash
A
Nazeri
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Susanne
S
Erk
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Eva J
EJ
Brandl
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Katrin
K
Charlet
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Anne
A
Beck
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Germany.
Sabine
S
Vollstädt-Klein
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Germany.
Anne
A
Jorde
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Germany.
Falk
F
Kiefer
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Andreas
A
Heinz
Department of Psychiatry, University of Heidelberg, Heidelberg, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Andreas
A
Meyer-Lindenberg
Cerebral Imaging Centre, Douglas Hospital Mental Health University Institute, Verdun, Canada.|Departments of Psychiatry, McGill University, Montreal, Canada.|Department of Biomedical Engineering, McGill University, Montreal, Canada.
M Mallar
0000-0002-0759-5508
MM
Chakravarty
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Henrik
H
Walter
D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D012044:Regression Analysis; D015203:Reproducibility of Results; D066127:White Matter / Q000000981:diagnostic imaging
TFCE_mediation; cortical thickness; diffusion magnetic resonance imaging; magnetic resonance imaging; mediation; nonparametric statistics; statistical data interpretation; surface area