Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications

Abstract

The contemporary value of animal pharmaco-electroencephalography (p-EEG)-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. While p-EEG in humans and animals has been shown to be closely related in terms of underlying neuronal substrates, both translational and back-translational approaches are being used to address extrapolation issues and optimize the translational validity of preclinical animal p-EEG paradigms and data. Present applications build further on animal p-EEG and pharmaco-sleep EEG findings, but also on stimulation protocols, more specifically pharmaco-event-related potentials. Pharmaceutical research into novel treatments for neurological and psychiatric diseases has employed an increasing number of pharmacological as well as transgenic models to assess the potential therapeutic involvement of different neurochemical systems and novel drug targets as well as underlying neuronal connectivity and synaptic function. Consequently, p-EEG studies, now also readily applied in modeled animals, continue to have an important role in drug discovery and development, with progressively more emphasis on its potential as a central readout for target engagement and as a (translational) functional marker of neuronal circuit processes underlying normal and pathological brain functioning. In a similar vein as was done for human p-EEG studies, the contribution of animal p-EEG studies can further benefit by adherence to guidelines for methodological standardization, which are presently under construction by the International Pharmaco-EEG Society (IPEG).

TAK-071, a muscarinic M1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys

“…In line with the previous studies that reported significant suppression of the scopolamine-induced increase in delta power band by AChE inhibitors in rats [28, 29], this study also demonstrated that donepezil counteracted the scopolamine-induced increases in alpha, theta, and delta power bands (Fig 2). Furthermore, both xanomeline and TAK-071 showed the potential to inhibit the scopolamine-induced qEEG spectral changes (Figs 3 and 4).…”

TAK-071, a muscarinic M1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys

“…After scopolamine treatment, qEEG resting state studies revealed an increase in delta power band and decrease in alpha power band. Moreover, AChE inhibitors such as donepezil, rivastigmine, and tacrine decreased delta power band after treatment with scopolamine in freely moving rats [28, 29].…”

Neurophysiological signals as predictive translational biomarkers for Alzheimer’s disease treatment: effects of donepezil on neuronal network oscillations in TgF344-AD rats

“…In recent years, electroencephalography (EEG) methodologies have emerged as useful tools for screening novel therapeutics. With its applicability in different species, high temporal resolution, and similarities in read-outs from animals and humans, EEG offers the promise to provide surrogate measures of drug efficacy and also to predict the impact of developmental compounds on endophenotypes associated with the disease in both clinical and preclinical settings [ 4 , 5 ]. Moreover, the relation of EEG measures in particular brain regions to certain functions, such as cognition, is suggested to be consistent between animals and humans [ 6 – 9 ].…”