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EEG biomarkers of target engagement, therapeutic effect, and disease process
Author(s) -
Featherstone Robert E.,
McMullen Mary F.,
Ward Katelyn R.,
Bang Jakyung,
Xiao Jane,
Siegel Steven J.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12745
Subject(s) - neurochemical , neuroscience , electroencephalography , schizophrenia (object oriented programming) , excitatory postsynaptic potential , nmda receptor , inhibitory postsynaptic potential , glutamate receptor , psychology , epilepsy , medicine , receptor , psychiatry
Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event‐related potentials and event‐related power within specific frequency ranges. Furthermore, clinical studies suggest that a subset of EEG biomarkers is associated with symptoms. This review addresses the relationship between EEG and behavior in preclinical models of N ‐methyl‐ d ‐aspartate (NMDA)‐receptor hypofunction, as well as how these models can be used to screen therapies. Data from schizophrenia patients are juxtaposed with data from animal models, and EEG and behavioral data from mice with disruption of NMDA receptors in excitatory and/or inhibitory neurons are then compared to the pattern observed in schizophrenia. Also discussed are results following exposure to potential therapeutic agents, including GABA B agonists. Furthermore, evidence demonstrates that elevated resting gamma power is associated with deficits in social interactions. Consistent with elevated baseline noise, excitatory neurons from transgenic mice show increased intrinsic excitability in in vitro –slice patch‐clamp studies across model systems. GABA B receptor agonists reduce this excitability, improve gamma‐band responses, and reverse behavioral deficits in mice. Data suggest that baseline gamma power is associated with social function and GABA B agonists may be useful for schizophrenia. Translational EEG biomarkers reflect target engagement and can contribute to the design of more efficient drug trials, likely accelerating the development of new therapeutics for central nervous system disorders.