Effects of anxiety state on N400 event-related brain potential response to unexpected semantic stimuli.

Emotional states can influence how people use meaningful context to make predictions about what comes next. To measure whether state anxiety influences such prediction, we used the N400 event-related brain potential (ERP) response to semantic stimuli, whose amplitude is smaller (less negative) when the stimulus is more predicted based on preceding context. Participants (n = 28) were randomized to one of two groups, who underwent either an "anxious-uncertainty" procedure previously shown to increase anxiety, or a control procedure. Both before and after this procedure, participants' ERPs were recorded while they viewed category definitions (e.g., "a type of fruit"), each followed by a target word that was either a high-typicality category exemplar ("apple"), low-typicality exemplar ("cherry"), or non-exemplar ("clamp") of the category. Participants' task was to respond by pressing one of two buttons to indicate whether the target represented a member of the category. As expected, based on previous work, overall, N400 amplitudes were largest (most negative) in response to non-exemplars, intermediate to low-typicality exemplars, and smallest to high-typicality exemplars. N400 amplitudes were larger to non-exemplars after the anxious-uncertainty procedure than after the control procedure. N400 amplitudes to both types of exemplars did not differ after the anxious-uncertainty procedure versus the control procedure. The results are consistent with participants devoting more neural resources to processing contextually unexpected items under anxious states, rather than anxiety facilitating processing of expected items.

Neurofilament light-chain (NfL) and 18 kDa translocator protein in early psychosis and its putative high-risk.

Evidence of elevated peripheral Neurofilament light-chain (NfL) as a biomarker of neuronal injury can be utilized to reveal nonspecific axonal damage, which could reflect altered neuroimmune function. To date, only a few studies have investigated NfL as a fluid biomarker in schizophrenia primarily, though none in its putative prodrome (Clinical High-Risk, CHR) or in untreated first-episode psychosis (FEP). Further, it is unknown whether peripheral NfL is associated with 18 kDa translocator protein (TSPO), a validated neuroimmune marker. In this secondary study, we investigated for the first time (1) serum NfL in early stages of psychosis including CHR and FEP as compared to healthy controls, and (2) examined its association with brain TSPO, using [18F]FEPPA positron emission tomography (PET). Further, in the exploratory analyses, we aimed to assess associations between serum NfL and symptom severity in patient group and cognitive impairment in the combined cohort. A large cohort of 84 participants including 27 FEP (24 antipsychotic-naive), 41 CHR (34 antipsychotic-naive) and 16 healthy controls underwent structural brain MRI and [18F]FEPPA PET scan and their blood samples were obtained and assessed for serum NfL concentrations. We found no significant differences in serum NfL levels across clinical groups, controlling for age. We also found no significant association between NfL levels and brain TSPO in the entire cohort. We observed a negative association between serum NfL and negative symptom severity in CHR. Our findings suggest that neither active neuroaxonal deterioration as measured with NfL nor associated neuroimmune activation (TSPO) is clearly identifiable in an early mostly untreated psychosis sample including its putative high-risk.

N400 event-related brain potential index of semantic processing and two-year clinical outcomes in persons at high risk for psychosis: A longitudinal study.

The N400 event-related brain potential (ERP) semantic priming effect reflects greater activation of contextually related versus unrelated concepts in long-term semantic memory. Deficits in this measure have been found in persons with schizophrenia and those at clinical high risk (CHR) for this disorder. In CHR patients, we previously found that these deficits predict poorer social functional outcomes after 1 year. In the present study, we tested whether these deficits predicted greater psychosis-spectrum symptom severity and functional impairment over 2 years. We measured N400 semantic priming effects at baseline in CHR patients (n = 47) who viewed prime words each followed by a related/unrelated target word at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured psychosis-spectrum symptoms using the Structured Interview for Prodromal Symptoms and role and social functioning with the Global Functioning: Role and Social scales, at baseline, 1 (n = 29) and 2 years (n = 25). There was a significant interaction between the N400 semantic priming effect at the 300-ms SOA and time on GF:Role scores, indicating that, contrary to expectations, smaller baseline N400 semantic priming effects were associated with more improvement in role functioning from baseline to Year 1, but baseline N400 priming effects did not predict role functioning at Year 2. N400 priming effects were not significantly associated with different trajectories in psychosis-spectrum symptoms or social functioning. Thus, CHR patients' N400 semantic priming effects did not predict clinical outcomes over 2 years, suggesting that this ERP measure may have greater value as a state or short-term prognostic neurophysiological biomarker.

Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

Interaction between peripheral and central immune markers in clinical high risk for psychosis.

Neuroinflammatory events prior to the diagnosis of schizophrenia may play a role in transition to illness. To date only one in-vivo study has investigated this association between peripheral proinflammatory cytokines and brain markers of inflammation (e.g., mitochondrial 18 kDa translocator protein, TSPO) in schizophrenia, but none in its putative prodrome. In this study, we primarily aimed to (Barron et al., 2017) test study group (clinical high-risk (CHR) and healthy controls) differences in peripheral inflammatory markers and test for any associations with symptom measures, (Hafizi et al., 2017a) investigate the interaction between brain TSPO levels (dorsolateral prefrontal cortex (DLPFC) and hippocampus) and peripheral inflammatory clusters (entire cohort and (CHR) group independently) within a relatively large group of individuals at CHR for psychosis (N = 38) and healthy controls (N = 20). Participants underwent structural brain magnetic resonance imaging (MRI) and TSPO [18F]FEPPA positron emission tomography (PET) scans. Serum samples were assessed for peripheral inflammatory markers (i.e., CRP and interleukins). For exploratory analysis, we aimed to examine cluster differences for symptom measures and identify independent peripheral predictors of brain TSPO expression. Here, we report increased IL-8 levels that are positively correlated with prodromal general symptom severity and showed trend-level association with apathy in CHR. We identified distinct inflammatory clusters characterized by inflammatory markers (IL-1 ß, IL-2, IFN-γ) that were comparable between entire cohort and CHR. TSPO levels did not differ between inflammatory clusters (entire cohort or CHR). Finally, we show that CRP, IL-1 ß, TNF-α, and IFN-γ levels were the independent peripheral predictors of brain TSPO expression. Thus, alterations in brain TSPO expression in response to inflammatory processes are not evident in CHR. Taken together, clustering by inflammatory status is a promising strategy to characterize the interaction between brain TSPO and peripheral markers of inflammation.

Atypical prediction error learning is associated with prodromal symptoms in individuals at clinical high risk for psychosis.

Reductions in the auditory mismatch negativity (MMN) have been well-demonstrated in schizophrenia rendering it a promising biomarker for understanding the emergence of psychosis. According to the predictive coding theory of psychosis, MMN impairments may reflect disturbances in hierarchical information processing driven by maladaptive precision-weighted prediction errors (pwPEs) and enhanced belief updating. We applied a hierarchical Bayesian model of learning to single-trial EEG data from an auditory oddball paradigm in 31 help-seeking antipsychotic-naive high-risk individuals and 23 healthy controls to understand the computational mechanisms underlying the auditory MMN. We found that low-level sensory and high-level volatility pwPE expression correlated with EEG amplitudes, coinciding with the timing of the MMN. Furthermore, we found that prodromal positive symptom severity was associated with increased expression of sensory pwPEs and higher-level belief uncertainty. Our findings provide support for the role of pwPEs in auditory MMN generation, and suggest that increased sensory pwPEs driven by changes in belief uncertainty may render the environment seemingly unpredictable. This may predispose high-risk individuals to delusion-like ideation to explain this experience. These results highlight the value of computational models for understanding the pathophysiological mechanisms of psychosis.

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia.

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.

Distinct profiles of psychological and neuropsychological functions underlying goal-directed pursuit in schizophrenia.

OBJECTIVES: Several components are known to underlie goal-directed pursuit, including executive, motivational and volitional functions. These were explored in schizophrenia spectrum disorders in order to identify subgroups with distinct profiles. METHODS: Multiple executive, motivational and volitional tests were administered to a sample of outpatients with schizophrenia spectrum diagnoses (n = 59) and controls (n = 63). Research questions included whether distinct profiles exist and whether some functions are impacted disproportionately. These questions were addressed via cluster analysis and profile analysis, respectively. RESULTS: Some such functions were significantly altered in schizophrenia while others were unaffected. Two distinct profiles emerged, one characterized by energizing deficits, reduced reward sensitivity and few subjective complaints; while another was characterized by markedly increased punishment sensitivity, intact reward sensitivity and substantial subjective reporting of avolitional symptoms and boredom susceptibility. CONCLUSION: These findings highlight the importance of considering distinct patterns of strengths and deficits in functions governing goal-directed pursuit in schizophrenia that demarcate identifiable subtypes. These distinctions have implications for treatment, assessment and research.

N400 event-related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study.

BACKGROUND: The N400 event-related brain potential (ERP) semantic priming effect is thought to reflect activation by meaningful stimuli of related concepts in semantic memory and has been found to be deficient in schizophrenia. We tested the hypothesis that, among individuals at clinical high risk (CHR) for psychosis, N400 semantic priming deficits predict worse symptomatic and functional outcomes after one year. METHODS: We measured N400 semantic priming at baseline in CHR patients (n = 47) and healthy control participants (n = 25) who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured patients' psychosis-like symptoms with the Scale of Prodromal Symptoms (SOPS) Positive subscale, and academic/occupational and social functioning with the Global Functioning (GF):Role and Social scales, respectively, at baseline and one-year follow-up (n = 29). RESULTS: CHR patients exhibited less N400 semantic priming than controls across SOAs; planned contrasts indicated this difference was significant at the 750-ms but not the 300-ms SOA. In patients, reduced N400 semantic priming at the 750-ms SOA was associated with lower GF:Social scores at follow-up, and greater GF:Social decrements from baseline to follow-up. Patients' N400 semantic priming was not associated with SOPS Positive or GF:Role scores at follow-up, or change in these from baseline to follow-up. CONCLUSIONS: In CHR patients, reduced N400 semantic priming at baseline predicted worse social functioning after one year, and greater decline in social functioning over this period. Thus, the N400 may be a useful prognostic biomarker of real-world functional outcome in CHR patients.

Decreased Gamma Auditory Steady-State Response Is Associated With Impaired Real-World Functioning in Unmedicated Patients at Clinical High Risk for Psychosis.

AIM: Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients' real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. METHODS: A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. RESULTS: In CHR patients, lower 40-Hz PLF correlated with lower social functioning. CONCLUSIONS: Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.

N400 event-related brain potential as an index of real-world and neurocognitive function in patients at clinical high risk for schizophrenia.

AIM: The N400 event-related potential is a neurophysiological index of cognitive processing of real-world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This 'N400 semantic priming effect' is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real-world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. METHODS: We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Decreased N400 semantic priming at the 300-ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750-ms SOA correlated with lower MCCB composite scores. CONCLUSIONS: Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.

Special Report on the Impact of the COVID-19 Pandemic on Clinical EEG and Research and Consensus Recommendations for the Safe Use of EEG.

INTRODUCTION: The global COVID-19 pandemic has affected the economy, daily life, and mental/physical health. The latter includes the use of electroencephalography (EEG) in clinical practice and research. We report a survey of the impact of COVID-19 on the use of clinical EEG in practice and research in several countries, and the recommendations of an international panel of experts for the safe application of EEG during and after this pandemic. METHODS: Fifteen clinicians from 8 different countries and 25 researchers from 13 different countries reported the impact of COVID-19 on their EEG activities, the procedures implemented in response to the COVID-19 pandemic, and precautions planned or already implemented during the reopening of EEG activities. RESULTS: Of the 15 clinical centers responding, 11 reported a total stoppage of all EEG activities, while 4 reduced the number of tests per day. In research settings, all 25 laboratories reported a complete stoppage of activity, with 7 laboratories reopening to some extent since initial closure. In both settings, recommended precautions for restarting or continuing EEG recording included strict hygienic rules, social distance, and assessment for infection symptoms among staff and patients/participants. CONCLUSIONS: The COVID-19 pandemic interfered with the use of EEG recordings in clinical practice and even more in clinical research. We suggest updated best practices to allow safe EEG recordings in both research and clinical settings. The continued use of EEG is important in those with psychiatric diseases, particularly in times of social alarm such as the COVID-19 pandemic.

Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.

BACKGROUND: The brain's endocannabinoid system, the primary target of cannabis, has been implicated in psychosis. The endocannabinoid anandamide is elevated in cerebrospinal fluid of patients with schizophrenia. Fatty acid amide hydrolase (FAAH) controls brain anandamide levels; however, it is unknown if FAAH is altered in vivo in psychosis or related to positive psychotic symptoms. METHODS: Twenty-seven patients with schizophrenia spectrum disorders and 36 healthy control subjects completed high-resolution positron emission tomography scans with the novel FAAH radioligand [11C]CURB and structural magnetic resonance imaging. Data were analyzed using the validated irreversible 2-tissue compartment model with a metabolite-corrected arterial input function. RESULTS: FAAH did not differ significantly between patients with psychotic disorders and healthy control subjects (F1,62.85 = 0.48, p = .49). In contrast, lower FAAH predicted greater positive psychotic symptom severity, with the strongest effect observed for the positive symptom dimension, which includes suspiciousness, delusions, unusual thought content, and hallucinations (F1,26.69 = 12.42, p = .002; Cohen's f = 0.42, large effect). Shorter duration of illness (F1,26.95 = 13.78, p = .001; Cohen's f = 0.39, medium to large effect) and duration of untreated psychosis predicted lower FAAH (F1,26.95 = 6.03, p = .021, Cohen's f = 0.27, medium effect). These results were not explained by past cannabis exposure or current intake of antipsychotic medications. FAAH exhibited marked differences across brain regions (F7,112.62 = 175.85, p < 1 × 10-56; Cohen's f > 1). Overall, FAAH was higher in female subjects than in male subjects (F1,62.84 = 10.05, p = .002; Cohen's f = 0.37). CONCLUSIONS: This first study of brain FAAH in psychosis indicates that FAAH may represent a biomarker of disease state of potential utility for clinical studies targeting psychotic symptoms or as a novel target for interventions to treat psychotic symptoms.

Religiosity is associated with less prediction of the typical: An event-related brain potential study.

Why are some people more religious than others? According to one hypothesis, people who strongly seek definitive explanations for situations with incomplete information are more likely to be religious. According to a different hypothesis, individuals with smaller "prediction error" responses to unexpected stimuli are more likely to discount evidence contradicting religious beliefs, predisposing them to maintain such beliefs. We sought neurophysiological evidence for these hypotheses using the N400 event-related potential (ERP), which is smaller to more contextually expected stimuli, reflecting prediction of probable completions for meaningful situations. We recorded ERPs from participants viewing category definitions followed by high-typicality category exemplar (HTE), low-typicality exemplar (LTE), or non-exemplar (NE) words. As expected, N400s were largest for NEs, intermediate for LTEs, and smallest for HTEs. Religiosity correlated with smaller N400 amplitude differences between HTEs and both LTEs and NEs. Less strong prediction of probable stimuli based on prior information may predispose to religiosity.

Negative symptoms in the clinical high-risk state for psychosis: Connection with cognition and primacy in impacting functioning.

AIM: In the clinical high-risk (CHR) state for psychosis, both negative symptoms and lower cognitive function have been associated with poorer daily functioning. Recent evidence suggests that negative symptoms share overlapping variability with cognition and may partially mediate the relationship between cognition and functioning. However, the nature of this overlap is unknown, and the reverse mediation model remains untested leaving the precise nature of these associations unclear. METHODS: In order to clarify these relationships, a sample of community-dwelling youth meeting CHR criteria was collected from a specialty CHR clinic (n = 91, mean age = 21, 63% male). Bootstrapping methods were then applied in a mediation analysis to test both negative symptoms and cognition as independent variables and mediating variables predicting social and role functioning in CHR individuals. Canonical correlation analysis was used to characterize the overlapping variability between negative symptoms and cognition. RESULTS: Support for a primary role of negative symptoms in predicting functioning and cognition was observed. Canonical correlation revealed a single dimension of overlap between the two symptom types (r = .62), represented by a strong correlation between negative symptoms in general and tasks involving verbal working memory, vigilance and social cognition specifically. A single cognitive factor composed primarily of these tasks was found to predict role functioning (adjusted R 2 = .04). CONCLUSIONS: The results highlight the importance of considering specific cognitive mechanisms overlapping with negative symptoms in research and rehabilitative practice in CHR populations, as well as the primary importance of targeting negative symptoms.

Relationships between cognitive event-related brain potential measures in patients at clinical high risk for psychosis.

Neurophysiological measures of cognitive functioning that are abnormal in patients with schizophrenia are promising candidate biomarkers for predicting development of psychosis in individuals at clinical high risk (CHR). We examined the relationships among event-related brain potential (ERP) measures of early sensory, pre-attentional, and attention-dependent cognition, in antipsychotic-naïve help-seeking CHR patients (n = 36) and healthy control participants (n = 22). These measures included the gamma auditory steady-state response (ASSR; early sensory); mismatch negativity (MMN) and P3a (pre-attentional); and N400 semantic priming effects - a measure of using meaningful context to predict related items - over a shorter and a longer time interval (attention-dependent). Compared to controls, CHR patients had significantly smaller P3a amplitudes (d = 0.62, p = 0.03) and N400 priming effects over the long interval (d = 0.64, p = 0.02). In CHR patients, gamma ASSR evoked power and phase-locking factor were correlated (r = 0.41, p = 0.03). Reductions in mismatch negativity (MMN) and P3a amplitudes were also correlated (r = -0.36, p = 0.04). Moreover, lower gamma ASSR evoked power correlated with smaller MMN amplitudes (r = -0.45, p = 0.02). MMN amplitude reduction was also associated with reduced N400 semantic priming over the shorter but not the longer interval (r = 0.52, p < 0.002). This pattern of results suggests that, in a subset of CHR patients, impairment in pre-attentional measures of early information processing may contribute to deficits in attention-dependent cognition involving rapid, more automatic processing, but may be independent from pathological processes affecting more controlled or strategic processing. Thus, combining neurophysiological indices of cognitive deficits in different domains offers promise for improving their predictive power as prognostic biomarkers of clinical outcome.

Validating mitochondrial electron transport chain content in individuals at clinical high risk for psychosis.

Altered mitochondrial electron transport chain function has been implicated in the pathophysiology and etiology of schizophrenia. To date, our previously published study (i.e. first cohort) is still the only study to demonstrate that mitochondrial electron transport chain is not altered in white blood cells from individuals at clinical high risk for psychosis. Here, we aimed to replicate our previous findings with an independent set of samples and validate the levels of mitochondrial complex I-V content in individuals at clinical high risk for psychosis. We demonstrated that the second cohort (i.e. validation cohort) expressed similar results as the first cohort. We combined the first cohort study with the second cohort and once more validated a lack of differential levels in mitochondrial complex I-V content between the two groups. In addition, we were able to validate a correlation between complex III content and prodromal negative symptom severity when the two cohorts studies were combined. Additionally, a correlation between complex V content and prodromal disorganization symptom severity was found when the two cohorts were combined. In conclusion, our results showed that dysfunction of the mitochondrial electron transport chain is not detected in peripheral blood mononuclear cells of individuals in the putative prodromal stage of schizophrenia.

Stress precedes negative symptom exacerbations in clinical high risk and early psychosis: A time-lagged experience sampling study.

The experience sampling method (ESM) has revealed associations between fluctuations in stress and positive symptoms in psychosis. It is unknown, however, how negative symptoms including anhedonia respond to stress. Stress is divided according to its source: event-related stress stemming from negative events, and activity-related stress stemming from engaging in tasks beyond one's skill or control. Anhedonia is divided into consummatory and anticipatory anhedonia, reflecting a lack of pleasure in current and expected activities. This study uses ESM to determine whether each form of anhedonia increases in response to stress. Antipsychotic-naïve individuals with first episode psychosis (n = 39), clinical high-risk states for psychosis (n = 44), and healthy controls (n = 34) responded to daily prompts on a palmtop computer for up to ten days by indicating levels of stress and anhedonia. Time-lagged multilevel modelling was employed to explore increases in anhedonia following increases in stress while controlling for prior levels of anhedonia. Mean levels of anhedonia were also compared across groups. Only activity-related stress produced increases in anhedonia. This effect did not vary between groups. Clinical groups showed greater overall levels of anhedonia than healthy controls, but did not differ from each other. Anhedonia responds only to activity-related stressors, suggesting that this form of stress has a specific causal role in anhedonia. The results also provide further evidence for global increases in anhedonia in antipsychotic-naïve psychosis spectrum individuals.

Spontaneous spatial navigation circuitry in schizophrenia spectrum disorders.

Spatial memory is core to wayfinding and everyday memory. Interestingly, individuals with schizophrenia using spatial navigation strategies (cognitive mapping) are impaired, whereas those using response-based (e.g., single-landmark) strategies show relatively intact memory performance. We observed abnormal brain communication in schizophrenia participants who used a spatial strategy during a virtual-reality navigation task, particularly between temporal and frontal brain regions. In contrast, schizophrenia participants using a response strategy recruited similar brain systems to healthy participants, but to a greater extent to support memory performance. These findings highlight that strategy use is an important consideration for understanding memory systems and navigation in schizophrenia.

The N400 event-related brain potential response: A window on deficits in predicting meaning in schizophrenia.

Schizophrenia is characterized by impairments in using past experience to predict what will happen next, at multiple levels of cognitive processing. The N400 event-related brain potential (ERP) waveform indexes our ability to use contextual information in combination with world knowledge to predict upcoming meaningful or semantic stimuli. N400 studies have provided evidence that patients with schizophrenia have deficits in such prediction. Some studies of schizophrenia patients have found these N400 semantic priming deficits to correlate with delusions, which frequently involve misinterpretations of meaningful relationships between objects or events, and to improve with antipsychotic treatment. Thus, these semantic priming deficits may reflect a neurocognitive mechanism of delusions, paralleling other cognitive domains in which prediction deficits are a proposed cause of schizophrenia symptoms.