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

Abstract

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.

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

“…Alterations in processes that regulate synaptic plasticity and PSD architecture may affect brain connectivity, disrupting the synchronized firing of those neurons organized in a high-frequency oscillation network (30–90 Hz/s), known as gamma waves, involved in cognition and memory functions [ 33 , 34 , 35 ]. Studies have associated altered gamma oscillations with neurological and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia [ 36 , 37 ]. Moreover, gamma oscillations were demonstrated to be modulated by antipsychotic treatment in preclinical studies [ 38 , 39 , 40 ].…”

Node centrality in MEG resting-state networks co-varies with neurotransmitter receptor and transporter density

“…2 E-J), Spearman’s correlation coefficient between node strength and each receptor’s or transporter’s density across parcels. We first assessed the GABA A and NMDA receptors, which through fast ionotropic transmission shape the generation of oscillations in local circuits of interacting glutamatergic excitatory pyramidal cells (PCs) and inhibitory GABAergic interneurons (INs) (Batista-Brito et al, 2018; Liley & Muthukumaraswamy, 2020; Lozano-Soldevilla et al, 2014; Lu et al, 2022; Middleton et al, 2008; Roopun, 2008). We found that both GABAa and NMDA receptor densities covaried positively with the PS node centrality in δ to α and γ bands, but with AC node centrality only in γ band (Fig.…”

“…We specifically established how the heterogeneity in receptor and transmitter densities influences networks of phase synchrony and amplitude correlations. One limitation of the current study is the lack of usable density maps for some important receptors such as GABA B that are known to be important for the generation of cortical oscillations in microcircuits (Liley & Muthukumaraswamy, 2020; Lozano-Soldevilla et al, 2014; Lu et al, 2022). Future studies will need to investigate how these microcircuits are influenced by the underlying neurotransmitter receptor and transmitter densities not only in resting state, but also during task (Boot et al, 2017; Cools, 2008; Puig & Gulledge, 2011).…”

Frequency-specific changes in prefrontal activity associated with maladaptive belief updating in volatile environments in euthymic bipolar disorder

“…Insufficient GABAergic neurotransmission and excessive glutamatergic system activity have previously been linked to electrophysiological alterations in BD [92]. Considering that mood stabilisers for BD, such as valproate and lithium, may have opposing effects on beta activity and potentially on beta/gamma connectivity [92,93], a promising avenue for future research is to assess the modulation of alpha-beta and gamma amplitude and connectivity during pwPE encoding in BD as potential markers for tracking treatment response and for diagnostic purposes. A key limitation of our study is the inclusion of patients on diverse psychiatric medications, including mood stabilisers, antipsychotics, and antidepressants.…”