15 Years of Microstate Research in Schizophrenia - Where Are We? A Meta-Analysis

Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.

Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia

Patients with schizophrenia show abnormal dynamics and structure of temporally ­coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs – default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) – and three EEG bands – theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback ­targeting prestates could be beneficial as task performance relies on the preparatory state of the brain.

Internet-based self-help for schizophrenia – risks and chances

Purpose: Schizophrenia is a severe mental disorder which is accompanied by an enormous individual and societal burden. Despite established efficacy of cognitive behavioral therapy (CBT) for schizophrenia, its dissemination into routine mental health care remains poor. Internet-based cognitive behavioral therapy in a self-help format helps to narrow the treatment gap in many mental disorders. Are Internet-based self-help programs, which are based on the principles of CBT, also feasible and viable for patients with schizophrenia? Methods: Mental health professionals (target N=50) as well as individuals with schizophrenia spectrum disorders (target N=50) reported their opinion regarding potential chances and risks of Internet-based self-help for schizophrenia in an online survey. Results: The preliminary data analysis of n=30 health professionals revealed a general acceptance of Internet-based programs for schizophrenia (53% acceptable, 47% acceptable after empirical evaluation) and specific contraindications (e.g., severe psychotic symptoms; 73%). People with schizophrenia highlighted the attractiveness of self-help interventions due to a wish for empowerment and for opportunities to strengthen self-efficacy. Conclusions: Risks, limitations and chances of Internet-based programs for patients with schizophrenia will be discussed.

Structural brain correlates of defective gesture performance in schizophrenia

INTRODUCTION The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS Patients performed poorer than controls in each gesture category (p < .001). Patients with deficits in producing meaningful gestures on command had reduced GM predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe (IPL) and superior temporal gyrus. CONCLUSIONS Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations. However, few associations between behavioral impairment and structural brain alterations appear specific to schizophrenia.

Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology scale and the five-factor model of the Positive and Negative Syndrome Scale

The aim was to examine to what extent the dimensions of the BPS map the five factors derived from the PANSS in order to explore the level of agreement of these alternative dimensional approaches in patients with schizophrenia. 149 inpatients with schizophrenia spectrum disorders were recruited. Psychopathological symptoms were assessed with the Bern Psychopathology Scale (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted to explore the association between the factors and the items of the BPS. The robustness of patterns was evaluated. An understandable overlap of both approaches was found for positive and negative symptoms and excitement. The PANSS positive factor was associated with symptoms of the affect domain in terms of both inhibition and disinhibition, the PANSS negative factor with symptoms of all three domains of the BPS as an inhibition and the PANSS excitement factor with an inhibition of the affect domain and a disinhibition of the language and motor domains. The results show that here is only a partial overlap between the system-specific approach of the BPS and the five-factor PANSS model. A longitudinal assessment of psychopathological symptoms would therefore be of interest.

Gesture performance in first- and multiple-episode patients with schizophrenia spectrum disorders

BACKGROUND/AIM Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. METHODS In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. RESULTS Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. CONCLUSIONS Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Disturbances of agency and ownership in schizophrenia: An auditory verbal event related potentials study

A ‘sense of self’ is essentially the ability to distinguish between self-generated and external stimuli. It consists of at least two very basic senses: a sense of agency and a sense of ownership. Disturbances seem to provide a basic deficit in many psychiatric diseases. The aim of our study was to manipulate those qualities separately in 28 patients with schizophrenia (14 auditory hallucinators and 14 non-hallucinators) and 28 healthy controls (HC) and to investigate the effects on the topographies and the power of the event-related potential (ERP). We performed a 76-channel EEG while the participants performed the task as in our previous paper. We computed ERPs and difference maps for the conditions and compared the amount of agency and ownership between the HC and the patients. Furthermore, we compared the global field power and the topographies of these effects. Our data showed effects of agency and ownership in the healthy controls and the hallucinator group and to a lesser degree in the non-hallucinator group. We found a reduction of the N100 during the presence of agency, and a bilateral temporal negativity related to the presence of ownership. For the agency effects, we found significant differences between HC and the patients. Contrary to the expectations, our findings were more pronounced in non-hallucinators, suggesting a more profoundly disturbed sense of agency compared to hallucinators. A contemporary increase of global field power in both patient groups indicates a compensatory recruitment of other mechanisms not normally associated with the processing of agency and ownership.