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.

Association between electroencephalographic modulation, psychotic-like experiences and cognitive performance in the general population.

AIM: An association between deficit of electroencephalographic (EEG) modulation during an odd-ball task and psychotic symptoms has been described in clinical samples, in agreement with the proposed role for altered salience in psychosis. To discard the possible influence of medication, the relationship between psychotic-like experiences and EEG modulation in the general population was explored. METHODS: EEG and psychotic-like experiences were assessed in 194 healthy subjects during a P300 paradigm. EEG modulation was assessed as changes from pre-stimulus to response windows in spectral entropy (SE, a measurement of signal irregularity), median frequency (MF, a quantifier of the frequency distribution of oscillatory activity) and theta, alpha, beta-1, beta-2 and gamma relative power (RP, a summary of the distribution of spectral components). RESULTS: A significant widespread decrease in SE and MF from baseline to response was found, with a significant increase in RP for theta and a decrease for higher frequency bands, supporting an increase in EEG regularity and a slowing of brain oscillations during the response. Furthermore, a significant association was found between SE modulation and distress of negative psychotic-like experiences, as well as between verbal memory and RP modulation for beta-1. Performance in verbal fluency was associated with the increase in theta RP during the response. CONCLUSION: EEG irregularity of healthy subjects decreased at the expense of a larger contribution of theta RP and a decreased contribution of fast frequency bands. Subjects with smaller modulation showed poorer cognitive scores and greater distress of negative psychotic-like experiences.

Neurobiological underpinnings of cognitive subtypes in psychoses: A cross-diagnostic cluster analysis.

Schizophrenia and bipolar disorder include patients with different characteristics, which may hamper the definition of biomarkers. One of the dimensions with greater heterogeneity among these patients is cognition. Recent studies support the identification of different patients' subgroups along the cognitive domain using cluster analysis. Our aim was to validate clusters defined on the basis of patients' cognitive status and to assess its relation with demographic, clinical and biological measurements. We hypothesized that subgroups characterized by different cognitive profiles would show differences in an array of biological data. Cognitive data from 198 patients (127 with chronic schizophrenia, 42 first episodes of schizophrenia and 29 bipolar patients) were analyzed by a K-means cluster approach and were compared on several clinical and biological variables. We also included 155 healthy controls for further comparisons. A two-cluster solution was selected, including a severely impaired group and a moderately impaired group. The severely impaired group was associated with higher illness duration and symptoms scores, lower thalamus and hippocampus volume, lower frontal connectivity and basal hypersynchrony in comparison to controls and the moderately impaired group. Moreover, both patients' groups showed lower cortical thickness and smaller functional connectivity modulation than healthy controls. This study supports the existence of different cognitive subgroups within the psychoses with different neurobiological underpinnings.

Identificacion of MRI-based psychosis subtypes: Replication and refinement.

The identification of the cerebral substrates of psychoses such as schizophrenia and bipolar disorder is likely hampered by its biological heterogeneity, which may contribute to the low replication of results in the field. In this study we aimed to replicate in a completely new sample and supplement the results of a previous study with additional data on this topic. In the aforementioned study we identified a schizophrenia cluster characterized by high mean cortical curvature and low cortical thickness, subcortical hypometabolism and progressive negative symptoms. Here, we have used magnetic resonance images from 61 schizophrenia and 28 bipolar patients, as well as 51 healthy controls and a cluster analysis to search for possible subgroups primarily characterized by cerebral structural data. Diffusion tensor imaging (fractional anisotropy, FA), cognition, clinical data and electroencephalographic (EEG) modulation during a P300 task were used to validate the possible clusters. Two clusters of patients were identified. The first cluster (29 schizophrenia and 18 bipolar patients) showed decreased cortical thickness and area values, as well as lower subcortical volumes and higher cortical curvature in some regions, as compared to the second cluster. This first cluster also showed decreased FA in frontal lobe connections and worse cognitive performance. Although this cluster also showed longer illness duration, there were first episode patients in both clusters and treatment doses and types were not different between clusters. Both clusters of patients showed decreased EEG task-related modulation. In conclusion, our data give additional support to a distinct biologically based cluster encompassing schizophrenia and bipolar disorder patients with cortical and subcortical alterations, hampered cortical connectivity and lower cognitive performance.

[Relationship between subclinical psychotic symptoms and cognitive performance in the general population]. / Relaciones entre síntomas psicóticos subclínicos y rendimiento cognitivo en la población general.

INTRODUCTION: Subclinical psychotic symptoms are associated to negative life outcomes in the general population, but their relationship with cognitive performance is still not well understood. Assessing the relationship between performance in cognitive domains and subclinical psychotic symptoms in the general population may also help understand the handicap attributed to clinical psychosis, in which these alterations are present. METHODS: Subclinical and cognitive assessments were obtained in 203 participants from the general population by means of the Community Assessment of Psychic Experiences, the Brief Assessment of Cognition in Schizophrenia, the Wechsler Adults Intelligence Scale and the Wisconsin Card Sorting Test. The positive and negative subclinical symptoms and their relationship with age and cognition were examined, followed by assessing the influence of subclinical depression scores on the possible relationships between those subclinical psychotic symptoms and cognitive deficits. RESULTS: Inverse relationships were found between frequency in the Community Assessment of Psychic Experiences positive dimension and motor speed, and frequency and distress in the Community Assessment of Psychic Experiences negative dimension and motor speed. A direct relationship was also found between distress scores of the positive dimension and executive functions. Both positive and negative subclinical symptoms were related to depression scores. CONCLUSIONS: Psychotic symptoms, similar to those in the clinical population, may be associated with cognitive deficits in the general population.

Modulation of brain network parameters associated with subclinical psychotic symptoms.

OBJECTIVE: Static deficits in small-world properties of brain networks have been described in clinical psychosis, but task-related modulation of network properties has been scarcely studied. Our aim was to assess the modulation of those properties and its association with subclinical psychosis and cognition in the general population. METHOD: Closeness centrality and small-worldness were compared between pre-stimulus baseline and response windows of an odd-ball task in 200 healthy individuals. The correlation between modulation of network parameters and clinical (scores in the Community Assessment of Psychological Experiences) and cognitive measures (performance in the dimensions included in the Brief Assessment of Cognition in Schizophrenia battery) was analyzed, as well as between these measures and the corresponding network parameters during baseline and response windows during task performance. RESULTS: In the theta band, closeness centrality decreased and small-worldness increased in the response window. Centrality and small-worldness modulation were, respectively, directly and inversely associated with subclinical symptoms. CONCLUSIONS: A widespread modulation of network properties in theta band was observed, with a transient increase of small-worldness during the response window, compatible with a transiently more integrated cortical activity associated to cognition. This supports the relevance of electroencephalography to study of normal and altered cognition and its substrates. A relative deficit in the ability to reorganize brain networks may contribute to subclinical psychotic symptoms.

Relaciones entre síntomas psicóticos subclínicos y rendimiento cognitivo en la población general / Relationship between subclinical psychotic symptoms and cognitive performance in the general population

Introducción. En la población general, los síntomas psicóticos subclínicos se han asociado con mayores dificultades funcionales en la vida real, pero desconocemos si estos síntomas están asociados a un peor rendimiento cognitivo. El estudio de la relación entre las alteraciones cognitivas y estos síntomas puede, además, ayudarnos a comprender mejor las dificultades que presentan los pacientes con psicosis, en los que estas alteraciones cognitivas están presentes. Métodos. Realizamos evaluaciones clínicas y cognitivas en 203 sujetos de la población general mediante los instrumentos Community Assessment of Psychic Experiences, Brief Assessment of Cognition in Schizophrenia, Wechsler Adult Intelligence Scale y Wisconsin Card Sorting Test. Se evaluó la relación de los síntomas psicóticos subclínicos positivos y negativos con la edad y el rendimiento cognitivo. Además, se evaluó la influencia de los síntomas depresivos subclínicos sobre la posible relación entre síntomas positivos y negativos subclínicos y las alteraciones cognitivas. Resultados. Encontramos una relación inversa del rendimiento en la prueba de velocidad motora tanto con la frecuencia de síntomas positivos como con el distrés y la frecuencia de los síntomas negativos. También encontramos una relación directa entre el distrés de los síntomas positivos y el rendimiento en función ejecutiva. La puntuación en síntomas depresivos subclínicos se asoció con ambas escalas subclínicas, positiva y negativa. Conclusiones. Los síntomas psicóticos subclínicos están relacionados con déficits cognitivos en la población general, similares a los observados en poblaciones clínicas (AU)

Introduction. Subclinical psychotic symptoms are associated to negative life outcomes in the general population, but their relationship with cognitive performance is still not well understood. Assessing the relationship between performance in cognitive domains and subclinical psychotic symptoms in the general population may also help understand the handicap attributed to clinical psychosis, in which these alterations are present. Methods. Subclinical and cognitive assessments were obtained in 203 participants from the general population by means of the Community Assessment of Psychic Experiences, the Brief Assessment of Cognition in Schizophrenia, the Wechsler Adults Intelligence Scale and the Wisconsin Card Sorting Test. The positive and negative subclinical symptoms and their relationship with age and cognition were examined, followed by assessing the influence of subclinical depression scores on the possible relationships between those subclinical psychotic symptoms and cognitive deficits. Results. Inverse relationships were found between frequency in the Community Assessment of Psychic Experiences positive dimension and motor speed, and frequency and distress in the Community Assessment of Psychic Experiences negative dimension and motor speed. A direct relationship was also found between distress scores of the positive dimension and executive functions. Both positive and negative subclinical symptoms were related to depression scores. Conclusions. Psychotic symptoms, similar to those in the clinical population, may be associated with cognitive deficits in the general population (AU)