Disruption of gamma-delta relationship related to working memory deficits in first-episode psychosis.

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45 Hz) and delta (0.5-4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.

Differences of temporal dynamics and signal complexity of gamma band oscillations in first-episode psychosis during a working memory task.

Gamma band oscillations participate in the temporal binding needed to synchronize cortical networks, involved in early sensory and short term memory processes. In earlier studies, alterations of these neurophysiological parameters have been found in psychotic disorders. To date no study has explored the temporal dynamics and signal complexity of gamma band oscillations in first episode psychosis (FEP). To address this issue, gamma band analysis was performed in 15 FEP patients and 18 healthy controls who successfully performed an adapted 2-back working memory task. Multiple linear and logistic regression models were computed to explore the relationship between the cognitive status and gamma oscillation changes over time. Based on regression model results, phase diagrams were constructed and their complexity was estimated using fractal dimension, a mathematical tool that describes shapes as numeric values. When adjusted for gamma values at time lags -3 to -4 ms and -15 to -16 ms, FEP patients displayed significantly higher time-dependent changes than controls, independently of the nature of the task. The present results are consistent with a discoordination of the activity of cortical generators engaged by the stimulus apparition in FEP patients, leading to a global binding deficit. In addition, fractal analysis showing higher complexity of gamma signal, confirmed this deficit. Our results provide evidence for recruitment of supplementary cortical generators as compensating mechanisms and yield further understanding for the pathophysiology cognitive impairments in FEP.

Effectiveness of a brief group cognitive behavioral therapy for auditory verbal hallucinations: a 6-month follow-up study.

The current study investigated the effectiveness of a group cognitive behavioral therapy for auditory verbal hallucinations (AVHs), the Voices Group. This consists of seven specific sessions. Forty-one participants with schizophrenic or schizoaffective disorders completed a battery of questionnaires. The severity of psychiatric symptoms, beliefs about voices, quality of life, self-esteem, clinical global impression, and functioning were assessed at baseline, before and after intervention, and at the 6-month follow-up. After intervention, there was a statistically significant reduction in the severity of AVHs. This result remained stable at follow-up. The dropout rate was high. Some differences were found in subjective experience of AVHs between the patients who completed the intervention and those who dropped out. Altogether, these findings suggest that a brief intervention has some positive benefits in patients struggling with voices, which remain stable over time.

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

BACKGROUND: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. METHODS: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. RESULTS: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. LIMITATIONS: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. CONCLUSION: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Persistence of Neuronal Alterations in Alcohol-Dependent Patients at Conclusion of the Gold Standard Withdrawal Treatment: Evidence From ERPs.

Background: One of the main challenges for clinicians is to ensure that alcohol withdrawal treatment is the most effective possible after discharge. To address this issue, we designed a pilot study to investigate the efficacy of the rehabilitation treatment on the main stages of information processing, using an electroencephalographic method. This topic is of main importance as relapse rates after alcohol withdrawal treatment remain very high, indicating that established treatment methods are not fully effective in all patients in the long run. Method: We examined in alcohol-dependent patients (ADP) the effects of the benzodiazepine-based standard detoxification program on event-related potential components at incoming (D0) and completion (D15) of the treatment, using tasks of increasing difficulty (with and without workload) during an auditory oddball target paradigm. Untreated non-alcohol-dependent-volunteers were used as matching controls. Results: At D0, ADP displayed significantly lower amplitude for all ERP components in both tasks, as compared to controls. At D15, this difference disappeared for the amplitude of the N1 component during the workload-free task, as well as the amplitude of the P3b for both tasks. Meanwhile, the amplitude of the N2 remained lower in both tasks for ADP. At D0, latencies of N2 and P3b in both task conditions were longer in ADP, as compared to controls, whilst the latency of N1 was unchanged. At D15, the N2 latency remained longer for the workload condition only, whereas the P3b latency remained longer for the workload-free task only. Conclusion: The present pilot results provide evidence for a persistence of impaired parameters of ERP components, especially the N2 component. This suggests that neural networks related to attention processing remain dysfunctional. Longitudinal long-term follow-up of these patients is mandatory for further assessment of a link between ERP alterations and a later risk of relapse.

False memory production in schizophrenia: A neurophysiological investigation.

BACKGROUND: The topic of false memory in schizophrenia has been well documented in earlier research contributions. To date, there is no study exploring the implications of specific neural networks during this phenomenon in patients suffering from schizophrenia. METHODS: We compared 17 patients suffering from psychosis (SCZ) to 33 healthy controls (HC) performing a verbal memory task designed to produce false memories, i.e. the Deese-Roediger-McDermott paradigm (DRM). Electroencephalography was used to specifically analyze the P2 and N400 event-related potentials components. RESULTS: The SCZ patients showed a reduced ability to distinguish between true and false memories as assessed by the A' index which was calculated based on the false and true memory rates. The morphology of the P2 differed in frontal electrode region with a lower amplitude in SCZ. In addition, the amplitude of N400 was more pronounced (more negative) in HC than in SCZ in centro-parietal electrode site. CONCLUSIONS: We suggest that the differences found in P2 amplitude are associated with difficulties of SCZ patients to efficiently compare item-specific features of a mnesic elements to incoming stimuli which impair the subsequent verbal memory information processing reflected by the N400 component amplitude decrease. These results are consistent with the idea that SCZ use a different strategy while they perform the DRM paradigm.

Asymmetric learning transfer between imagined viewer- and object-rotations: evidence of a hierarchical organization of spatial reference frames.

Neural resources subserving spatial processing in either egocentric or allocentric reference frames are, at least partly, dissociated. However, it is unclear whether these two types of representations are independent or whether they interact. We investigated this question using a learning transfer paradigm. The experiment and material were designed so that they could be used in a clinical setting. Here, we tested healthy subjects in an imagined viewer-rotation task and an imagined object-rotation task. The order of the tasks was counterbalanced across subjects. The results showed that subjects who did the viewer-rotation task first had fewer errors and shorter latencies of response in the object-rotation task, whereas subjects who did the object-rotation task first had little if any advantage in the viewer-rotation task. In other words, the results revealed an asymmetric learning transfer between tasks, which suggests that spatial representations are hierarchically organized. Specifically, the results indicate that the viewer-rotation task engaged allocentric representations and egocentric representations, whereas the object-rotation task engaged only egocentric representations.

Working memory impairments in first-episode psychosis and chronic schizophrenia.

Working memory (WM) impairments are core cognitive deficits in patients with schizophrenia linked to prefrontal cortical dysfunctions. Determining the differences between early phases of illness allows a better understanding of its course and constitutes an important guide for treatment. The present cross-sectional study examined differences of working memory functions between 33 first-episode and 29 chronic schizophrenic patients, as well as 64 healthy controls. On the basis of a two-back visual-verbal computerized working memory task, reaction time was slower and accuracy was worse in both patient groups than in controls. Test variables, however, were not significantly different between the patient groups, suggesting stability of the deficits over time. Effect size accuracy variables nevertheless showed larger deficits in chronic patients.

Comparing Mental Health across Distinct Groups of Users of Psychedelics, MDMA, Psychostimulants, and Cannabis.

Differences in mental health (MH) of users of distinct psychoactive substances have been shown. Both substance use (SU) and MH in users are influenced by stressful life events. This study compared MH parameters in distinct groups of substance users and evaluated the impact of stress factors on these outcomes. Data stem from the longitudinal Swiss Cohort Study on Substance Use Risk Factors (C-SURF) involving 4,475 young adult men. Distinct groups were created for the past 12 months' use of psychedelics, MDMA, psychostimulants, and cannabis. MH measurements (depressive symptoms, overall MH, perceived stress, life satisfaction) were used as outcome variables, while indicators of past family functioning and stressful life events served as covariates. The MH of psychedelics users was not significantly different from the no-drug-use group, whereas poorer MH was found in the other SU groups. Observed effects were influenced by the tested stress factors. The absence of association between use of psychedelics and worsening of MH deserves further investigation in male and female samples. Stressful life experiences must be considered when assessing the MH of users of illicit substances. These findings suggest that some men practice SU as self-medication to cope with life adversity.

Deficits in neurocognition, theory of mind, and social functioning in patients with schizophrenic disorders: are they related?

In schizophrenic disorders, impairments in social functioning, neurocognition, and theory of mind (ToM) are frequently reported but little is known about the relationships between them. The aim of this study is twofold: (a) to compare neurocognition, social-functioning, and ToM in patients and controls and (b) to investigate whether impairments in these domains are related to psychiatric symptoms. Participants were 16 outpatients with schizophrenic disorders (DSM-IV), and 16 healthy controls. We administered neuropsychological tests, ToM, social functioning, and psychopathology measures. Patients and controls differed on most neurocognitive variables (memory, attention, executive functions). We also found significant differences in 1 ToM factor and 2 social measures. The latter were the only 2 related to manic-hostility and negative symptoms subscores of Brief Psychiatric Rating Scale. Our findings suggest that there is no direct relation between neurocognitive impairments and social dysfunctions.

Impaired social cognition in schizophrenia during the Ultimatum Game: An EEG study.

BACKGROUND: Schizophrenia has a core feature of cognitive dysfunctions. Since these deficits are predictive for patients' functional outcome, understanding their origin is of great importance to improve their daily lives. A specific component of the deficit involves social decision-making, which can be studied using the Ultimatum Game (UG). In this task, a "proposer" proposes a share of money to a "responder", who can either accept or reject this offer. If the responder accepts the proposal, both win money. If the responder refuses, both players end up with nothing. Therefore, the UG evaluates decision-making strategies and social interaction. METHODS: We compared the neuronal bases of schizophrenic patients with healthy controls, while performing the UG. Electroencephalography (EEG) was used to find differences in the event-related potential (ERP) components typical for the UG, namely the P2 and feedback-related negativity (FRN). Source reconstruction was further used to define the origin of these differences. RESULTS: In the proposer condition, no differences were found in amplitude of the P2 and FRN components. In contrast, in the responder condition, significant differences were found for the amplitude of the FRN (p=0.009). Using source reconstruction, a different activation in a border zone of the dorsolateral and the medial prefrontal cortex was revealed in schizophrenic patients to underlie this component. CONCLUSIONS: We suggest that the difference found in the FRN amplitude is associated with difficulties of patients in interpreting another's behavior. Although schizophrenic patients correctly activate neuronal bases in the proposer condition, they were not able to activate the same networks in the responder condition, thereby exposing their difficulties in social interaction.

Differences in Social Decision-Making between Proposers and Responders during the Ultimatum Game: An EEG Study.

The Ultimatum Game (UG) is a typical paradigm to investigate social decision-making. Although the behavior of humans in this task is already well established, the underlying brain processes remain poorly understood. Previous investigations using event-related potentials (ERPs) revealed three major components related to cognitive processes in participants engaged in the responder condition, the early ERP component P2, the feedback-related negativity (FRN) and a late positive wave (late positive component, LPC). However, the comparison of the ERP waveforms between the responder and proposer conditions has never been studied. Therefore, to investigate condition-related electrophysiological changes, we applied the UG paradigm and compared parameters of the P2, LPC and FRN components in twenty healthy participants. For the responder condition, we found a significantly decreased amplitude and delayed latency for the P2 component, whereas the mean amplitudes of the LPC and FRN increased compared to the proposer condition. Additionally, the proposer condition elicited an early component consisting of a negative deflection around 190 ms, in the upward slope of the P2, probably as a result of early conflict-related processing. Using independent component analysis (ICA), we extracted one functional component time-locked to this deflection, and with source reconstruction (LAURA) we found the anterior cingulate cortex (ACC) as one of the underlying sources. Overall, our findings indicate that intensity and time-course of neuronal systems engaged in the decision-making processes diverge between both UG conditions, suggesting differential cognitive processes. Understanding the electrophysiological bases of decision-making and social interactions in controls could be useful to further detect which steps are impaired in psychiatric patients in their ability to attribute mental states (such as beliefs, intents, or desires) to oneself and others. This ability is called mentalizing (also known as theory of mind).

Assessment of mental workload: A new electrophysiological method based on intra-block averaging of ERP amplitudes.

The present study contributes to the current debate about electrophysiological measurements of mental workload. Specifically, the allocation of attentional resources during different complexity levels of tasks and its changes over time are of great interest. Therefore, we investigated mental workload using tasks varying in difficulty during an auditory oddball target paradigm. For data analysis, we applied a novel method to compute event-related potentials (ERPs) by intra-block epoch averaging of P2, P3a and P3b amplitude components for the infrequent target stimuli. We obtained eight consecutive blocks of 5 epochs each, which allowed us to develop an electrophysiological parameter to measure mental workload. In both the easy and the more constraining tasks, the amplitude of P2 decreased beginning with the second block of the sequence. In contrast, the amplitudes of P3a and P3b components linearly decreased following the repetition of the target in the more constraining task, but not in the easy task. Statistical analysis revealed intra-block differences on amplitudes of ERPs of interest between the easy and the more constraining tasks, confirming this method as a measure to assess mental workload. Since a subject is his own control, the present method represents an electrophysiological parameter for individual measurement of mental workload and may therefore be applicable in clinical routine.

Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning.

BACKGROUND: The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode, acutely psychotic patients. METHOD: In a double-blind, fixed-dose study, 49 acutely psychotic, neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were randomly assigned to 2 or 4 mg/day of risperidone. Treatment efficacy was measured using the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, The Clinical Global Impressions scale, and the Social and Occupational Functioning Assessment Scale. Fine motor functions were assessed using a computerized device (the Vienna Test System) and were compared with those of a control group of 20 healthy subjects who were matched for age, gender, and educational level. RESULTS: Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive (p < .0001) and negative (p < .01) symptoms at 8 weeks. Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale, computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks. No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions. CONCLUSION: The 2 doses of risperidone did not differ in terms of clinical improvement, but the 2-mg/day dose produced fewer fine motor dysfunctions. These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis.

The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression.

The 24-item Brief Psychiatric Rating Scale (BPRS, version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Visual scan paths in first-episode schizophrenia and cannabis-induced psychosis.

OBJECTIVE: Patterns of successive saccades and fixations (scan paths) that are made while viewing images are often spatially restricted in schizophrenia, but the relation with cannabis-induced psychosis has not been examined. We used higher-order statistical methods to examine spatiotemporal characteristics of scan paths to determine whether viewing behaviour was distinguishable on a continuum. METHODS: Patients with early acute first-episode paranoid schizophrenia (SCH; n = 11), cannabis-induced psychosis (CIP; n = 6) and unaffected control subjects (n = 22) undertook a task requiring free viewing of facial, fractal and landscape images for 5 seconds while their eye movements were recorded. Frequencies and distributions of saccades and fixations were calculated in relation to image regions examined during each trial. RESULTS: Findings were independent of image category, indicating generalized scanning deficits. Compared with control subjects, patients with SCH and CIP made fewer saccades and fewer fixations of longer duration. In turn, the spatial distribution of fixations in CIP patients was more clustered than in SCH and control subjects. The diversity of features fixated in subjects with CIP was also lower than in SCH patients and control subjects. CONCLUSION: A continuous approach to characterizing scan path changes in different phenotypes suggests that CIP shares some of the abnormalities of SCH but can be distinguished with measures that are sensitive to cognitive strategies active or inhibited during visual exploration.