Association between abnormal brain oscillations and cognitive performance in patients with bipolar disorder: Molecular mechanisms and clinical evidence

Brain oscillations have gained great attention in neuroscience during recent decades as functional building blocks of cognitive-sensory processes. Research has shown that oscillations in "alpha," "beta," "gamma," "delta," and "theta" frequency windows are highly modified in brain pathology, including in patients with cognitive impairment like bipolar disorder (BD). The study of changes in brain oscillations can provide fundamental knowledge for exploring neurophysiological biomarkers in cognitive impairment. The present article reviews findings from the role and molecular basis of abnormal neural oscillation and synchronization in the symptoms of patients with BD. An overview of the results clearly demonstrates that, in cognitive-sensory processes, resting and evoked/event-related electroencephalogram (EEG) spectra in the delta, theta, alpha, beta, and gamma bands are abnormally changed in patients with BD showing psychotic features. Abnormal oscillations have been found to be associated with several neural dysfunctions and abnormalities contributing to BD, including abnormal GABAergic neurotransmission signaling, hippocampal cell discharge, abnormal hippocampal neurogenesis, impaired cadherin and synaptic contact-based cell adhesion processes, extended lateral ventricles, decreased prefrontal cortical gray matter, and decreased hippocampal volume. Mechanistically, impairment in calcium voltage-gated channel subunit alpha1 I, neurotrophic tyrosine receptor kinase proteins, genes involved in brain neurogenesis and synaptogenesis like WNT3 and ACTG2, genes involved in the cell adhesion process like CDH12 and DISC1, and gamma-aminobutyric acid (GABA) signaling have been reported as the main molecular contributors to the abnormalities in resting-state low-frequency oscillations in BD patients. Findings also showed the association of impaired synaptic connections and disrupted membrane potential with abnormal beta/gamma oscillatory activity in patients with BD. Of note, the synaptic GABA neurotransmitter has been found to be a fundamental requirement for the occurrence of long-distance synchronous gamma oscillations necessary for coordinating the activity of neural networks between various brain regions.