Functional network properties in schizophrenia and bipolar disorder assessed with high-density electroencephalography.

BACKGROUND: The study of the cortical functional network properties in schizophrenia (SZ) may benefit from the use of graph theory parameters applied to high-density electroencephalography (EEG). Connectivity Strength (CS) assesses global synchrony of the network, and Shannon Graph Complexity (SGC) summarizes the network distribution of link weights and allows distinguishing between primary and secondary pathways. Their joint use may help in understanding the underpinnings of the functional network hyperactivation and task-related hypomodulation previously described in psychoses. METHODS: We used 64-sensor EEG recordings during a P300 oddball task in 128 SZ patients (96 chronic, CR, and 32 first episodes, FE), as well as 46 bipolar disorder (BD) patients, and 92 healthy controls (HC). Pre-stimulus and modulation (task-response minus pre-stimulus windows values) of CS and SGC were assessed in the theta band (4-8 Hz) and the broadband (4-70 Hz). RESULTS: Compared to HC, SZ patients (CR and FE) showed significantly higher pre-stimulus CS values in the broadband, and both SZ and BD patients showed lower theta-band CS modulation. SGC modulation values, both theta-band and broadband, were also abnormally reduced in CR patients. Statistically significant relationships were found in the theta band between SGC modulation and both CS pre-stimulus and modulation values in patients. CS altered measures in patients were additionally related to their cognitive outcome and negative symptoms. A primary role of antipsychotics in these results was ruled out. CONCLUSIONS: Our results linking SGC and CS alterations in psychotic patients supported a hyperactive and hypomodulatory network mainly involving connections in secondary pathways.

Search for schizophrenia and bipolar biotypes using functional network properties.

INTRODUCTION: Recent studies support the identification of valid subtypes within schizophrenia and bipolar disorder using cluster analysis. Our aim was to identify meaningful biotypes of psychosis based on network properties of the electroencephalogram. We hypothesized that these parameters would be more altered in a subgroup of patients also characterized by more severe deficits in other clinical, cognitive, and biological measurements. METHODS: A clustering analysis was performed using the electroencephalogram-based network parameters derived from graph-theory obtained during a P300 task of 137 schizophrenia (of them, 35 first episodes) and 46 bipolar patients. Both prestimulus and modulation of the electroencephalogram were included in the analysis. Demographic, clinical, cognitive, structural cerebral data, and the modulation of the spectral entropy of the electroencephalogram were compared between clusters. Data from 158 healthy controls were included for further comparisons. RESULTS: We identified two clusters of patients. One cluster presented higher prestimulus connectivity strength, clustering coefficient, path-length, and lower small-world index compared to controls. The modulation of clustering coefficient and path-length parameters was smaller in the former cluster, which also showed an altered structural connectivity network and a widespread cortical thinning. The other cluster of patients did not show significant differences with controls in the functional network properties. No significant differences were found between patients´ clusters in first episodes and bipolar proportions, symptoms scores, cognitive performance, or spectral entropy modulation. CONCLUSION: These data support the existence of a subgroup within psychosis with altered global properties of functional and structural connectivity.

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

Background: The synchronized activity of distributed neural assemblies ­ reflected in the electroencephalogram (EEG) ­ underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored. Methods: We assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 werein their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters. Results: We found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory. Limitations: All patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes. Conclusion: Spectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.