title: Evaluation of multiple comparison correction procedures in drug assessment studies using LORETA maps.
abstract: The identification of the brain regions involved in the neuropharmacological action is a potential procedure for drug development. These regions are commonly determined by the voxels showing significant statistical differences after comparing placebo-induced effects with drug-elicited effects. LORETA is an electroencephalography (EEG) source imaging technique frequently used to identify brain structures affected by the drug. The aim of the present study was to evaluate different methods for the correction of multiple comparisons in the LORETA maps. These methods which have been commonly used in neuroimaging and also simulated studies have been applied on a real case of pharmaco-EEG study where the effects of increasing benzodiazepine doses on the central nervous system measured by LORETA were investigated. Data consisted of EEG recordings obtained from nine volunteers who received single oral doses of alprazolam 0.25, 0.5, and 1 mg, and placebo in a randomized crossover double-blind design. The identification of active regions was highly dependent on the selected multiple test correction procedure. The combined criteria approach known as cluster mass was useful to reveal that increasing drug doses led to higher intensity and spread of the pharmacologically induced changes in intracerebral current density.
authors.affiliation: Department of Automatic Control, Biomedical Engineering Research Center, Universitat Politècnica de Catalunya. BarcelonaTech (UPC), Barcelona, Spain.|Barcelona College of Industrial Engineering (EUETIB), UPC, Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Joan Francesc
authors.initials: JF
authors.lastname: Alonso
authors.affiliation: Department of Automatic Control, Biomedical Engineering Research Center, Universitat Politècnica de Catalunya. BarcelonaTech (UPC), Barcelona, Spain. sergio.romero-lafuente@upc.edu.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. sergio.romero-lafuente@upc.edu.
authors.forename: Sergio
authors.initials: S
authors.lastname: Romero
authors.affiliation: Department of Automatic Control, Biomedical Engineering Research Center, Universitat Politècnica de Catalunya. BarcelonaTech (UPC), Barcelona, Spain.|Barcelona College of Industrial Engineering (EUETIB), UPC, Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Mañanas
authors.affiliation: Department of Automatic Control, Biomedical Engineering Research Center, Universitat Politècnica de Catalunya. BarcelonaTech (UPC), Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Drug Research Center, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Department of Pharmacology and Therapeutics, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|CIBER de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
authors.affiliation: Drug Research Center, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Department of Pharmacology and Therapeutics, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|CIBER de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Manel José
authors.initials: MJ
authors.lastname: Barbanoj
mesh_terms: D000328:Adult; D000465:Algorithms; D000525:Alprazolam / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D004569:Electroencephalography / Q000379:methods*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D002491:Central Nervous System Agents; D000525:Alprazolam
keywords: Alprazolam; Cluster mass; EEG tomography; LORETA; Multiple testing; Nonparametric permutation test