Non-invasive quantification of drug-related EEG changes in non-human primates

Ann Iturra-Mena, PhD

McLean Hospital
Non-invasive quantification of drug-related EEG changes in non-human primates

Scientific Abstract

Background: The use of electroencephalography (EEG) in pharmacology offers sensitive methods to detect the influence of drugs on brain functioning, either for monitoring of drug toxicity in the central nervous system or for predicting clinical response to treatment. Unfortunately, despite the increasing sophistication of in-vivo electrophysiology in preclinical research, its use in behavioral pharmacology has been limited.

Methods: The aim of the present study was to design and to empirically test a novel non-invasive EEG methodology for the quantification of drug-related changes in the brain oscillatory activity of awake squirrel monkeys. In these experiments, bipolar surface electrodes located on the frontal area of the head were used to obtain passive EEG recording data. Once subjects were acclimated to the placement of scalp electrodes while seated in a customized primate chair, the effects of saline (0.3 ml) and two doses of the benzodiazepine midazolam, 0.3 mg/kg and 1 mg/kg, were studied in separate test sessions. Each session included a 10-min baseline recording before i.m. injection of the drug or saline and a 30-min recording period following the injection.

Results: The results showed dose-dependent and, following 1 mg/kg midazolam, consistent spectral changes from baseline in the theta, alpha and beta frequency bands.

Conclusions: Overall, these preliminary data indicate that this non-invasive EEG methodology provides a promising translational method to detect changes in electrical brain activity induced by pharmacological agents in non-human primates.

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Ann Iturra-Mena, PhD, Carol A. Paronis, PhD, Jack Bergman, PhD