title: False positive rates in Voxel-based Morphometry studies of the human brain: should we be worried?
abstract: Voxel-based Morphometry (VBM) is a widely used automated technique for the analysis of neuroanatomical images. Despite its popularity within the neuroimaging community, there are outstanding concerns about its potential susceptibility to false positive findings. Here we review the main methodological factors that are known to influence the results of VBM studies comparing two groups of subjects. We then use two large, open-access data sets to empirically estimate false positive rates and how these depend on sample size, degree of smoothing and modulation. Our review and investigation provide three main results: (i) when groups of equal size are compared false positive rate is not higher than expected, i.e. about 5%; (ii) the sample size, degree of smoothing and modulation do not appear to influence false positive rate; (iii) when they exist, false positive findings are randomly distributed across the brain. These results provide reassurance that VBM studies comparing groups are not vulnerable to the higher than expected false positive rates that are evident in single case VBM.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom; Center for Studies and Research in Cognitive Neuroscience (CSRNC), University of Bologna, Viale Europa 980, 47023 Cesena, Italy. Electronic address: cristina.scarpazza@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scarpazza
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tognin
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom; Department of Psychology, University of Padua, Via Venezia 12, 35131 Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Frisciata
authors.affiliation: Department of Psychology, University of Padua, Via Venezia 12, 35131 Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sartori
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
mesh_terms: D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D001931:Brain Mapping; D005189:False Positive Reactions; D006801:Humans; D059906:Neuroimaging
keywords: Balanced design; False positive rate; Neuroimaging; Unbalanced design; Voxel-based Morphometry