Sleep Organisation in Depression and Schizophrenia: Index of Endogenous Periodicity of Sleep as a State Marker [Retracted]

Background: Sleep disorders are frequent symptoms described in psychiatric patients with major depression or schizophrenia. These patients also exhibit changes in the sleep architecture measured by polysomnography (PSG) during sleep. The aim of the present study was to identify potential biomarkers that would facilitate the diagnosis based on polysomnography (PSG) measurements.Subjects and Methods: 30 patients with schizophrenia, 30 patients with major depression and 30 healthy control subjects were investigated in the present study. The mean age in the group with schizophrenia was 36.73 (SD 6.43), in the group of patients with depression 40.77 (SD 7.66), in the healthy controls group 34.40 (SD 5.70). The gender distribution was as follows: 18 male, 12 female in the group with schizophrenia; in the group of patients with depression 11 male, 19 female; in the control group 16 male and 14 female. All subjects underwent polysomnography (PSG) for a minimum time of 8 hours according to the criteria of Rechtschaffen & Kales (1968). The following polysomnographic (PSG) parameters were analyzed: sleep latency (SL), total sleep time (TST), waking time after sleep onset (WTASO), number of awakenings (NAW), slow wave sleep (SWS), rapid eye movement sleep (REM), rapid eye movement sleep latency (REML), first REM period (REM 1), and first NREM period (NREM 1). We tested the potential of multiple sleep variables to predict diagnosis in different groups by using linear discriminate analysis (LDA).Results: There were significant differences in polysomnography (PSG) variables between healthy control subjects and psychiatric patients (total sleep time, sleep latency, number of awakenings, time of awakening after sleep onset, REM 1 latency, REM 1 and index of endogenous periodicity). Importantly, LDA was able to predict the correct diagnosis in 88% of all cases.Conclusions: The presented analysis showed commonalities and differences in polysomnography (PSG) changes in patients with major depressive disorder and in patients with schizophrenia. Our results underline the potential of polysomnography (PSG) measurements to facilitate diagnostic processes

Aufmerksamkeitskontrolle von Attributionsprozessen in Schizophrenie

In patients with schizophrenia, the misattribution of self-generated events to an external source is associated with self-recognition deficits and the presence of psychotic symptoms. The aim of the present study was to investigate how this misattribution is influenced by dysfunction of attentional processing, which is also impaired in schizophrenia. I conducted two different studies. In both studies participant’s expectancies were manipulated using visual cues that were either congruent (valid) or incongruent (invalid) with the speech. The source (self/alien) and the acoustic quality (undistorted/distorted) of the speech were also manipulated. First, twentythree patients with schizophrenia, with hallucinations and delusions (H/D patients) and twentythree matched healthy controls (HC) were tested for the behavioral study. Later on, twenty patients with first episode psychosis (FEP) and twenty matched healthy controls (HC) underwent functional Magnetic Resonance Imaging (fMRI) while listening to prerecorded speech. The results of the behavioral part of the study showed that H/D patients exhibited increased error rates comparing to HC, when listening to the distorted self spoken words, misidentifying their own speech as produced by others. Importantly, patients made significantly more errors across all the invalid cue conditions. This suggested not only the presence of pathological misattribution bias, but also an inadequate balance between top-down and bottom-up attentional processes in patients, which could be responsible for misattribution of the ambiguous sensory material. Analysis of fMRI data showed that FEP patients when listening to self-generated speech preceded by an invalid (alien) cue, relative to HC showed a strong trend to misidentify their own speech as an other person's. The patient group had reduced activation in the right middle temporal gyrus (MTG) and left precuneus (Pc) relative to HC. Within the FEP group, the level of activation in the right MTG was negatively correlated with the severity of their positive psychotic symptoms. I conclude that impaired attentional modulation in schizophrenia may contribute to the tendency for FEP patients to misattribute the source of self-generated material, and this may be mediated through the right MTG and Pc, regions that are involved in both self-referential processing and the integration of sensory information.Schizophrene Patienten neigen dazu selbstgenerierte Handlungen auf externe Quellen zu misattribuieren. Dieser Bias ist assoziiert mit kognitiven Defiziten im Bereich der Selbsterkennung sowie mit psychotischen Symptomen. Das Ziel der präsentierten Studien ist es, zu untersuchen in wie weit dieser Misattributionsbias durch Aufmerksamkeitsprozesse beeinflusst wird, welche ebenfalls in schizophrenen Patienten beeinträchtigt sind. Ich führte zwei Studien durch in welchen die Probanden unterscheiden sollten, ob ein auditiv präsentiertes Wort in der eigenen Stimme oder einer fremden Stimme dargeboten wurde. Dabei wurden die Erwartungen der Probanden manipuliert durch visuelle Hinweisreize die entweder kongruent oder inkongruent zu einem auditiven Stimulus waren. Zudem wurde die akustische Qualität (unverzerrt / verzerrt) manipuliert. In der ersten Studie wurden 23 Patienten mit Schizophrenie sowie 23 gesunde Probanden in einem behavioralen Design untersucht. In der zweiten Studie wurden bei 20 Patienten mit Schizophrenie sowie bei 20 gesunden Probanden das gleiche Paradigma mittels fMRT untersucht. In der behavioralen Studie zeigte sich bei Patienten mit Schizophrenie im Vergleich zu gesunden Probanden eine erhöhte Fehlerrate und somit eine Tendenz die eigene Stimme zu missattribuieren, wenn selbstgesprochene Wörter verzerrt präsentiert wurden. Interessanterweise zeigten Patienten in allen Bedingungen mit inkongruenten Hinweisreizen eine signifikant erhöhte Fehlerrate. Dies lässt vermuten, dass bei schizophrenen Patienten ein generelles Muster kognitiver Beeinträchtigung vorliegt. Möglicherweise zeigen Patienten auf Grund einer Dysbalance von top-down und bottom-up gesteuerten Aufmerksamkeitsprozessen, eine beeinträchtigte Leistung bei der Attribuierung inkongruenter Stimuli. In der fMRT-Studie zeigten schizophrene Patienten eine ausgeprägte Tendenz ihre eigene Stimme als eine fremde Stimme zu misattribuieren, wenn inkongruente Hinweisreize präsentiert wurden. Dabei zeigten Patienten eine reduzierte Aktivität im rechten mittleren Temporallappen sowie im linken Precuneus. Zudem zeigte sich eine negative Korrelation zwischen der Aktivität im rechten mittleren Temporallappen und der Ausprägung der positiven Symptomatik. Daher ist anzunehmen, dass möglichweise eine beeinträchtigte Balance zwischen top-down und bottom-up gesteuerten Aufmerksamkeitsprozessen zum Misattributionbias in schizophrenen Patienten beiträgt. Zudem ist dieser Einfluss assoziiert mit Aktivität in Hirnregionen, die in der Integration sensorischer Information sowie in der Verabeitung selbstreferentieller Information involviert sind, wie der rechte mittlere Temporallappen sowie der Precuneu

Modeling Social Sensory Processing During Social Computerized Cognitive Training for Psychosis Spectrum: The Resting-State Approach

Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. Here, we investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are (1) related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and (2) associated with unique resting-state functional connectivity (rsFC). Methods: Twenty-six ROP patients completed 10 h of CCT over the period of 4–6 weeks. Subject-specific improvement in one CCT exercise targeting early sensory processing—a speeded facial Emotion Matching Task (EMT)—was studied as potential proxy for target engagement. Based on the median split of SPC from the EMT, two patient groups were created. Resting-state activity was collected at baseline, and bold time series were extracted from two major default mode network (DMN) hubs: left medial prefrontal cortex (mPFC) and left posterior cingulate cortex (PCC). Seed rsFC analysis was performed using standardized Pearson correlation matrices, generated between the average time course for each seed and each voxel in the brain. Results: Based on SPC, we distinguished improvers—i.e., participants who showed impaired performance at baseline and reached the EMT psychophysical threshold during CCT—from maintainers—i.e., those who showed intact EMT performance at baseline and sustained the EMT psychophysical threshold throughout CCT. Compared to maintainers, improvers showed an increase of rsFC at rest between PCC and left superior and medial frontal regions and the cerebellum. Compared to improvers, maintainers showed increased rsFC at baseline between PCC and superior temporal and insular regions bilaterally. Conclusions: In ROP patients with an increase of connectivity at rest in the default mode network, social CCT is still able to induce sensory processing changes that however do not translate into social cognitive gains. Future studies should investigate if impairments in short-term synaptic plasticity are responsible for this lack of response and can be remediated by pharmacological augmentation during CCT

Detecting the Psychosis Prodrome Across High-Risk Populations Using Neuroanatomical Biomarkers

To date, the MRI-based individualized prediction of psychosis has only been demonstrated in single-site studies. It remains unclear if MRI biomarkers generalize across different centers and MR scanners and represent accurate surrogates of the risk for developing this devastating illness. Therefore, we assessed whether a MRI-based prediction system identified patients with a later disease transition among 73 clinically defined high-risk persons recruited at two different early recognition centers. Prognostic performance was measured using cross-validation, independent test validation, and Kaplan-Meier survival analysis. Transition outcomes were correctly predicted in 80% of test cases (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given a 54-month transition risk of 45% across both centers, MRI-based predictors provided a 36%-increase of prognostic certainty. After stratifying individuals into low-, intermediate-, and high-risk groups using the predictor's decision score, the high- vs low-risk groups had median psychosis-free survival times of 5 vs 51 months and transition rates of 88% vs 8%. The predictor's decision function involved gray matter volume alterations in prefrontal, perisylvian, and subcortical structures. Our results support the existence of a cross-center neuroanatomical signature of emerging psychosis enabling individualized risk staging across different high-risk populations. Supplementary results revealed that (1) potentially confounding between-site differences were effectively mitigated using statistical correction methods, and (2) the detection of the prodromal signature considerably depended on the available sample sizes. These observations pave the way for future multicenter studies, which may ultimately facilitate the neurobiological refinement of risk criteria and personalized preventive therapies based on individualized risk profiling tool

Deciphering reward-based decision-making in schizophrenia: a meta-analysis and behavioral modeling of the Iowa Gambling Task

Background: Patients with schizophrenia (SZP) have been reported to exhibit impairments in reward-based decision-making, but results are heterogeneous with multiple potential confounds such as age, intelligence level, clinical symptoms or medication, making it difficult to evaluate the robustness of these impairments. Methods: We conducted a meta-analysis of studies comparing the performance of SZP and healthy controls (HC) in the Iowa Gambling Task (IGT) as well as comprehensive analyses based on subject-level data (n = 303 SZP, n = 188 HC) to investigate reward-based decision-making in SZP. To quantify differences in the influence of individual deck features (immediate gain, gain frequency, net loss) between SZP and HC, we additionally employed a least-squares model. Results: SZP showed statistically significant suboptimal decisions as indicated by disadvantageous deck choices (d from 0.51 to −0.62) and lower net scores (d from −0.35 to −1.03) in a meta-analysis of k = 29 samples (n = 1127 SZP, n = 1149 HC) and these results were confirmed in a complementary subject-level analysis. Moreover, decision-making in SZP was characterized by a relative overweighting of immediate gain and net losses and an underweighting of gain frequency. Moderator analyses revealed that in part, decision-making in the IGT was moderated by intelligence level, medication and general symptom scores. Conclusion: Our results indicate robust impairments in reward-based decision-making in SZP and suggest that decreased cognitive resources, such as working memory, may contribute to these alterations

Correspondence Between Resting-State and Episodic Memory-Task Related Networks in Elderly Subjects

Resting-state fMRI studies demonstrated temporally synchronous fluctuations in brain activity among ensembles of brain regions, suggesting the existence of intrinsic functional networks. A spatial match between some of the resting-state networks and regional brain activation during cognitive tasks has been noted, suggesting that resting-state networks support particular cognitive abilities. However, the spatial match and predictive value of any resting-state network and regional brain activation during episodic memory is only poorly understood. In order to address this research gap, we obtained fMRI acquired both during rest and a face-name association task in 38 healthy elderly subjects. In separate independent component analyses, networks of correlated brain activity during rest or the episodic memory task were identified. For the independent components identified for task-based fMRI, the design matrix of successful encoding or retrieval trials was regressed against the time course of each of the component to identify significantly activated networks. Spatial regression was used to assess the match of resting-state networks against those related to successful memory encoding or retrieval. We found that resting-state networks covering the medial temporal, middle temporal, and frontal areas showed increased activity during successful encoding. Resting-state networks located within posterior brain regions showed increased activity during successful recognition. However, the level of resting-state network connectivity was not predictive of the task-related activity in these networks. These results suggest that a circumscribed number of functional networks detectable during rest become engaged during successful episodic memory. However, higher intrinsic connectivity at rest may not translate into higher network expression during episodic memory

Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease

Introduction: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. Method: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). Results: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. Conclusions: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function

The left frontal cortex supports reserve in aging by enhancing functional network efficiency

Background: Recent evidence from fMRI studies suggests that functional hubs, i.e. highly connected brain regions, are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC-connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer’s disease. These results suggest that LFC-connectivity supports reserve capacity alleviating memory decline. An open question is, however, why LFC-connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFCconnectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities. Methods: We assessed fMRI during a face-name association learning task in 26 healthy cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC-connectivity to key memory networks including the default-mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses in order to test the association between LFC-connectivity to the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC-connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN smallworldness. Lastly, we tested network small-worldness as a predictor of memory performance. Results: We found that higher LFC-connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC-connectivity mediated the association between education and higher small-worldness in the DMN and DAN. Further, higher small-worldness of these networks predicted better performance in the memory task. Conclusions: The current results suggest that higher education-related LFC-connectivity to key memory networks during a memory task is associated with higher network efficiency and thus enhanced reserve of memory abilities in aging

General psychopathology links burden of recent life events and psychotic symptoms in a network approach

Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that general symptoms would mediate between recent life events and psychotic symptoms. We analyzed baseline data of patients at clinical high risk for psychosis and with recent-onset psychosis (n = 547) from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. In a network analysis, we modeled links between the burden of recent life events and all individual symptoms of the Positive and Negative Syndrome Scale before and after controlling for childhood trauma. To investigate the longitudinal associations between burden of recent life events and symptoms, we analyzed multiwave panel data from seven timepoints up to month 18. Corroborating our hypothesis, burden of recent life events was connected to positive and negative symptoms through general psychopathology, specifically depression, guilt feelings, anxiety and tension, even after controlling for childhood trauma. Longitudinal modeling indicated that on average, burden of recent life events preceded general psychopathology in the individual. In line with the theory of an affective pathway to psychosis, recent life events may lead to psychotic symptoms via heightened emotional distress. Life events may be one driving force of unspecific, general psychopathology described as characteristic of early phases of the psychosis spectrum, offering promising avenues for interventions