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Hum Brain Mapp. 2018 Jun;39(6):2289-2302. doi: 10.1002/hbm.24007. Epub 2018 Feb 15.

Statistical inference in brain graphs using threshold-free network-based statistics.

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Medical Psychology Unit, Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Catalonia, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic de Barcelona, Barcelona, Catalonia, Spain.
Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona. Institute of Neuroscience, University of Barcelona, Barcelona, Catalonia, Spain.
Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.


The description of brain networks as graphs where nodes represent different brain regions and edges represent a measure of connectivity between a pair of nodes is an increasingly used approach in neuroimaging research. The development of powerful methods for edge-wise group-level statistical inference in brain graphs while controlling for multiple-testing associated false-positive rates, however, remains a difficult task. In this study, we use simulated data to assess the properties of threshold-free network-based statistics (TFNBS). The TFNBS combines threshold-free cluster enhancement, a method commonly used in voxel-wise statistical inference, and network-based statistic (NBS), which is frequently used for statistical analysis of brain graphs. Unlike the NBS, TFNBS generates edge-wise significance values and does not require the a priori definition of a hard cluster-defining threshold. Other test parameters, nonetheless, need to be set. We show that it is possible to find parameters that make TFNBS sensitive to strong and topologically clustered effects, while appropriately controlling false-positive rates. Our results show that the TFNBS is an adequate technique for the statistical assessment of brain graphs.


connectomics; functional connectivity; network-based statistic; structural connectivity; threshold-free cluster enhancement

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