EEG Topography and Tomography (LORETA) in the Classification and Evaluation of the Pharmacodynamics of Psychotropic Drugs

Abstract

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

Influence of bromazepam on cortical interhemispheric coherence

“…In other words, electroenchephalography is responsive to the unique characteristics of psychoactive substances 1 . In this context, the EEG has been widely employed in the assessment of electrophysiological changes induced by distinct medications.…”

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

“…The empirical validity of LORETA has been established in a large number of studies [86] covering various EEG research fields, such as psychiatry [87,88], neurology [89,90], neuropsychopharmacology [91] and sleep medicine [92]. Further, the co-registration of LORETA with other neuroimaging methods has shown good correspondence of effects [93,94].…”

The influence of bromazepam on cortical power distribution

“…The effects of single oral doses of bromazepam (9 mg) and diazepam (10 mg) in EEG data were analyzed for thirteen male adult volunteers and an analogous result was reached: increased beta and decreased alpha activity. Such changes seem to be characteristic for benzodiazepines (Saletu et al 2006). Ohtani et al (2002) conducted one of the few studies that specifically analyzed the effects of 3 mg bromazepam, on a sample of 12 healthy male volunteers.…”