Topography of activation deficits in schizophrenia during P300 task related to cognition and structural connectivity.

BACKGROUND: The study of cerebral underpinnings of schizophrenia may benefit from the high temporal resolution of electromagnetic techniques, but its spatial resolution is low. However, source imaging approaches such as low-resolution brain electromagnetic tomography (LORETA) allow for an acceptable compromise between spatial and temporal resolutions. METHODS: We combined LORETA with 32 channels and 3-Tesla diffusion magnetic resonance (Dmr) to study cerebral dysfunction in 38 schizophrenia patients (17 first episodes, FE), compared to 53 healthy controls. The EEG was acquired with subjects performing an odd-ball task. Analyses included an adaptive window of interest to take into account the interindividual variability of P300 latency. We compared source activation patters to distractor (P3a) and target (P3b) tones within- and between-groups. RESULTS: Patients showed a reduced activation in anterior cingulate and lateral and medial prefrontal cortices, as well as inferior/orbital frontal regions. This was also found in the FE patients alone. The activation was directly related to IQ in the patients and controls and to working memory performance in controls. Symptoms were unrelated to source activation. Fractional anisotropy in the tracts connecting lateral prefrontal and anterior cingulate regions predicted source activation in these regions in the patients. CONCLUSIONS: These results replicate the source activation deficit found in a previous study with smaller sample size and a lower number of sensors and suggest an association between structural connectivity deficits and functional alterations.

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.

Social cognition in psychosis: Predictors and effects of META-cognitive training.

Social cognition deficits are found in schizophrenia and bipolar disorder, but its neural underpinnings are poorly understood. Given the complexity of psychological functions underlying this kind of cognition, we hypothesized that alterations in global structural connectivity could contribute to those deficits. To test this hypothesis, we studied a group of schizophrenia and bipolar patients with connectomics based on diffusion magnetic resonance imaging and assessments of general and social cognition. The latter was assessed using the Mayer, Salovey and Caruso Emotional Intelligence Test (MSCEIT) for emotional intelligence and the Spanish Group for Schizophrenia Treatment Optimization (Grupo Español para la OPtimización del Tratamiento de la Esquizofrenia, GEOPTE) test for behavioral aspects of social cognition. Graph theory applied to fractional anisotropy for the connections among cortical regions was used to obtain the small-world (SW) index of the structural connectivity network. In addition, we assessed the possibility of predicting the response of social cognition deficits to Meta-cognitive Training based on their possible underpinnings in a subgroup of patients. Patients showed lower scores in emotional intelligence and behavioral social cognition. MSCEIT scores were associated with SW index and working memory, and GEOPTE scores were related to verbal memory. Improvement in social cognition after Meta-cognitive Training was associated with lower scores of the social cognition in the baseline, according to the GEOPTE scale. Our findings support structural connectivity as one of the factors underlying emotional intelligence in schizophrenia, and the use of Meta-cognitive Training to improve social cognition in patients with larger deficits.

Structural connectivity in schizophrenia and bipolar disorder: Effects of chronicity and antipsychotic treatment.

Previous studies based on graph theory parameters applied to diffusion tensor imaging support an alteration of the global properties of structural connectivity network in schizophrenia. However, the specificity of this alteration and its possible relation with chronicity and treatment have received small attention. We have assessed small-world (SW) and connectivity strength indexes of the structural network built using fractional anisotropy values of the white matter tracts connecting 84 cortical and subcortical regions in 25 chronic and 18 first episode (FE) schizophrenia and 24 bipolar patients and 28 healthy controls. Chronic schizophrenia and bipolar patients showed significantly smaller SW and connectivity strength indexes in comparison with controls and FE patients. SW reduction was driven by increased averaged path-length (PL) values. Illness duration but not treatment doses were negatively associated with connectivity strength, SW and PL in patients. Bipolar patients exposed to antipsychotics did not differ in SW or connectivity strength from bipolar patients without such an exposure. Executive functions and social cognition were related to SW index in the schizophrenia group. Our results support a role for chronicity but not treatment in structural network alterations in major psychoses, which may not differ between schizophrenia and bipolar disorder, and may hamper cognition.