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.

Relation between EEG resting-state power and modulation of P300 task-related activity in theta band in schizophrenia.

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.