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 with drugelicited 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 9 volunteers who received single oral doses of alprazolam 0.25 mg, 0.5 mg and 1 mg, and placebo in a randomized cross-over 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 pharmacologicallyinduced changes in intracerebral current density.

On the Physiological Modulation and Potential Mechanisms Underlying Parieto-Occipital Alpha Oscillations

“…They bind to GABA A receptors and enhance chloride conductance by increasing its channel-opening frequency (Riss et al, 2008 ), as opposed to maintaining the channels open (as anesthetics and barbiturates do). Interestingly, a large variety of benzodiazepine type drugs using a wide range of dosages have been shown to produce a consistent decrease in parieto-occipital alpha power during resting state (Fink et al, 1976 ; Bond and Lader, 1982 ; Golombok and Lader, 1984 ; Koopmans et al, 1988 ; Van Steveninck et al, 1993 ; Feshchenko et al, 1997 ; Liley et al, 2003 ; Boeijinga et al, 2004 ; Fingelkurts et al, 2004 ; Schreckenberger et al, 2004 ; Connemann et al, 2005 ; Ahveninen et al, 2007 ; Yoto et al, 2012 ; Alonso et al, 2015 ; Nutt et al, 2015 ; Lozano-Soldevilla et al, 2016 ) and task conditions (van Leeuwen et al, 1995 ; Gevins et al, 2002 ; Muñoz-Torres et al, 2011 ; Saxena et al, 2013 ; Lozano-Soldevilla et al, 2014 ). Reports of benzodiazepine studies finding posterior alpha power increases (Tran et al, 2004 ; Nikulin et al, 2005 ; Hall et al, 2010 ; Nutt et al, 2015 ), frequency modulations (Liley et al, 2003 ), or just null results (Urata et al, 1996 ; Jensen et al, 2005 ; Muthukumaraswamy et al, 2013b ; Campbell et al, 2014 ) are less common within the literature.…”

Increased Temporal Lobe Beta Activity in Boys With Attention-Deficit Hyperactivity Disorder by LORETA Analysis

“…EEG is a non-invasive and convenient tool for studying brain function. Low-resolution electromagnetic tomography (LORETA) is an EEG source imaging technique that is frequently used to identify affected brain structures in patients with neurological diseases (Alonso et al, 2015 ), such as the seizure onset zone in patients with drug-resistant epilepsy (Staljanssens et al, 2017 ). In patients with moderate or severe obstructive sleep apnea, LORETA can be used to localize the generators of EEG activity in separate EEG frequency bands.…”

Delay Maturation in Occipital Lobe in Girls With Inattention Subtype of Attention-Deficit Hyperactivity Disorder

“…14 It is an EEG source imaging technique frequently used to identify brain structures affected by neurological diseases. 15 For example, Staljanssens et al 16 used LORETA to identify the seizure onset zone in patients with drug-resistant epilepsy. In patients with moderate or severe obstructive sleep apnea, LORETA was used to localize the generators of EEG activity in separate EEG frequency bands.…”