EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil

Abstract

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Guidelines for the Recording and Evaluation of Pharmaco-Sleep Studies in Man: The International Pharmaco-EEG Society (IPEG)

“…Most interesting from a methodological point of view is the finding that all 4 source localisation methods revealed similar results. The similar findings for the various inverse solutions and the physiologically meaningful results obtained from source localisation based not only on high-density but also on rather low-density EEG recordings [103,255,262] clearly justify the utilisation of these methods in pharmaco-sleep studies. However, it needs to be stressed that full details of the applied source localisation method with all its underlying assumptions (e.g.…”

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

“…Functional imaging of modafinil A Gozzi et al activation of fronto-cortical areas is relevant for translational research, as it reconciles preclinical functional mapping data, in which the involvement of fronto-cortical areas has not been consistently observed (Lin et al, 1996;Fiocchi et al, 2009;Engber et al, 1998;Scammell et al, 2000), with the increasing evidence in humans of a cortical modulation by the drug in normal (Saletu et al, 2007;Joo et al, 2008) and impaired states (Hunter et al, 2006;Spence et al, 2005;Saletu et al, 2004;Thomas and Kwong, 2006). The fronto-cortical activation is also consistent with the improved cognitive performance observed in rodent behavioral tasks upon MOD administration at doses similar to those employed in the present study (Tsanov et al, 2007;Beracochea et al, 2001Beracochea et al, , 2003Dawson et al, 2010).…”

Identifying target regions for vigilance improvement under hormone replacement therapy in postmenopausal syndrome patients by means of electroencephalographic tomography (LORETA)

“…In this new version, the solution space is restricted to cortical gray matter and the hippocampus, as determined in the Digitized Probability Atlas (Brain Imaging Center, Montreal, Neurologic Institute) based on the Talairach Human Brain Atlas. Thus, LORETA combines the high time resolution of the EEG with source localization methods that permit a truly threedimensional tomography of electrical brain activity, which makes it possible to answer the question whether a drug works within the brain (Anderer et al 2000;Saletu et al 2002aSaletu et al , 2004.…”