Title:
Brain oscillations as biomarkers in neuropsychiatric disorders: following an interactive panel discussion and synopsis.

Abstract:
This survey covers the potential use of neurophysiological changes as a biomarker in four neuropsychiatric diseases (attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), bipolar disorder (BD), and schizophrenia (SZ)). Great developments have been made in the search of biomarkers in these disorders, especially in AD. Nevertheless, there is a tremendous need to develop an efficient, low-cost, potentially portable, non-invasive biomarker in the diagnosis, course, or treatment of the above-mentioned disorders. Electrophysiological methods would provide a tool that would reflect functional brain dynamic changes within milliseconds and also may be used as an ensemble of biomarkers that is greatly needed in the evaluation of cognitive changes seen in these disorders. The strategies for measuring cognitive changes include spontaneous electroencephalography (EEG), sensory evoked oscillation (SEO), and event-related oscillations (ERO). Further selective connectivity deficit in sensory or cognitive networks is reflected by coherence measurements. Possible candidate biomarkers discussed in an interactive panel can be summarized as follows: for ADHD: (a) elevation of delta and theta, (b) diminished alpha and beta responses in spontaneous EEG; for SZ: (a) decrease of ERO gamma responses, (b) decreased ERO in all other frequency ranges, (c) invariant ERO gamma response in relation to working memory demand; for euthymic BD: (a) decreased event-related gamma coherence, (b) decreased alpha in ERO and in spontaneous EEG; for manic BD: (a) lower alpha and higher beta in ERO, (b) decreased event-related gamma coherence, (c) lower alpha and beta in ERO after valproate; and for AD: (a) decreased alpha and beta, and increased theta and delta in spontaneous EEG, (b) hyperexcitability of motor cortices as shown by transcortical magnetic stimulation, (c) hyperexcitability of visual sensory cortex as indicated by increased SEO theta responses, (d) lower delta ERO, (e) lower delta, theta, and alpha event-related coherence, (f) higher theta synchrony and higher alpha event-related coherence in cholinergically treated AD subjects. In further research in the search for biomarkers, multimodal methods should be introduced to electrophysiology for validation purposes. Also, providing the protocols for standardization and harmonization of user-friendly acquisition or analysis methods that would be applied in larger cohort populations should be used to incorporate these electrophysiologic methods into the clinical criteria. In an extension to conventional anatomical, biochemical and brain imaging biomarkers, the use of neurophysiologic markers may lead to new applications for functional interpretrations and also the possibility to monitor treatments tailored for individuals.