title: Unbiased cluster estimation of electrophysiological brain response.
abstract: Recent increase in the size and complexity of electrophysiological data from multidimensional electroencephalography (EEG) and magnetoencephalography (MEG) studies has prompted the development of sophisticated statistical frameworks for data analysis. One of the main challenges for such frameworks is the multiple comparisons problem, where the large number of statistical tests performed within a high-dimensional dataset lead to an increased risk of Type I errors (false positives). A solution to this problem, cluster analysis, applies the biologically-motivated knowledge of correlation between adjacent voxels in one or more dimensions of the dataset to correct for the multiple comparisons problem and detect true neurophysiological effects. Cluster-based methods provide increased sensitivity towards detecting neurophysiological events compared to conservative methods such as Bonferroni correction, but are limited by their dependency on an initial cluster-forming statistical threshold (e.g. t-score, alpha) obstructing precise comparisons of results across studies.
  
  
  
  Rather than selecting a single threshold value, unbiased cluster estimation (UCE) computes a significance distribution across all possible threshold values to provide an unbiased overall significance value.
  
  
  
  UCE functions as a novel extension to existing cluster analysis methods.
  
  
  
  Using data from EEG combined with brain stimulation study, we showed the impact of statistical threshold on outcome measures and introduction of bias. We showed the application of UCE for different study designs (e.g., within-group, between-group comparisons).
  
  
  
  We propose that researchers consider employing UCE for multidimensional EEG/MEG datasets toward an unbiased comparison of results between subjects, groups, and studies.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Frehlich
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Luis Garcia
authors.initials: LG
authors.lastname: Dominguez
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sravya
authors.initials: S
authors.lastname: Atluri
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Radhu
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yinming
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address: faranak.farzan@camh.ca.
authors.forename: Faranak
authors.initials: F
authors.lastname: Farzan
mesh_terms: D001921:Brain / Q000502:physiology*; D016000:Cluster Analysis; D004569:Electroencephalography / Q000379:methods*; D006801:Humans; D015225:Magnetoencephalography / Q000379:methods; D012107:Research Design; D012815:Signal Processing, Computer-Assisted; D018709:Statistics, Nonparametric; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
keywords: Brain mapping; Cluster analysis; Correction for multiple comparison; Electroencephalography; Magnetoencephalography; Statistical frameworks; Transcranial magnetic stimulation