Metacognitive training for psychosis (MCT): past, present, and future.

This article provides an overview and retrospective on metacognitive training for psychosis (MCT), which first appeared approximately 2 decades ago. We recount how our empirical understanding of psychosis at that time led to the first preliminary version of the program. We describe setbacks and challenges that led to major changes, including revisions to existing modules (e.g., more focus on metacognitive variables, particularly on decision confidence as one of the primary targets of treatment) and the creation of new modules addressing mood, as well as attempts to improve sustainability of effects via homework exercises and a smartphone app ( www.uke.de/mct_app ). We have also enhanced dissemination efforts by creating new culturally sensitive language versions and facilitating low-threshold training through e-learning courses ( www.uke.de/e-mct ). Finally, we discuss several meta-analyses on the efficacy of MCT that have been published over the last decade. While reviews were initially inconsistent, possibly reflecting the insufficient statistical power and lower design quality of the first MCT studies, more recent meta-analyses have confirmed the efficacy of MCT on positive symptoms, insight, and cognitive biases, which has led to the inclusion of MCT in some national treatment guidelines for schizophrenia.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Functional Delineation of Prefrontal Networks Underlying Working Memory in Schizophrenia: A Cross-data-set Examination.

BACKGROUND: Working memory (WM) impairment in schizophrenia substantially impacts functional outcome. Although the dorsolateral pFC has been implicated in such impairment, a more comprehensive examination of brain networks comprising pFC is warranted. The present research used a whole-brain, multi-experiment analysis to delineate task-related networks comprising pFC. Activity was examined in schizophrenia patients across a variety of cognitive demands. METHODS: One hundred schizophrenia patients and 102 healthy controls completed one of four fMRI tasks: a Sternberg verbal WM task, a visuospatial WM task, a Stroop set-switching task, and a thought generation task (TGT). Task-related networks were identified using multi-experiment constrained PCA for fMRI. Effects of task conditions and group differences were examined using mixed-model ANOVA on the task-related time series. Correlations between task performance and network engagement were also performed. RESULTS: Four spatially and temporally distinct networks with pFC activation emerged and were postulated to subserve (1) internal attention, (2) auditory-motor attention, (3) motor responses, and (4) task energizing. The "energizing" network-engaged during WM encoding and diminished in patients-exhibited consistent trend relationships with WM capacity across different data sets. The dorsolateral-prefrontal-cortex-dominated "internal attention" network exhibited some evidence of hypoactivity in patients, but was not correlated with WM performance. CONCLUSIONS: Multi-experiment analysis allowed delineation of task-related, pFC-anchored networks across different cognitive constructs. Given the results with respect to the early-responding "energizing" network, WM deficits in schizophrenia may arise from disruption in the "energization" process described by Donald Stuss' model of pFC functions.

Stability and similarity of the pediatric connectome as developmental measures.

Patterns of functional connectivity are unique at the individual level, enabling test-retest matching algorithms to identify a subject from among a group using only their functional connectome. Recent findings show that accuracies of these algorithms in children increase with age. Relatedly, the persistence of functional connectivity (FC) patterns across tasks and rest also increases with age. This study investigated the hypothesis that within-subject stability and between-subject similarity of the whole-brain pediatric connectome are developmentally relevant outcomes. Using data from 210 help-seeking children and adolescents, ages 6-21 years (Healthy Brain Network Biobank), we computed whole-brain FC matrices for each participant during two different movies (MovieDM and MovieTP) and two runs of task-free rest (all from a single scan session) and fed these matrices to a test-retest matching algorithm. We replicated the finding that matching accuracies for children and youth (ages 6-21 years) are low (18-44%), and that cross-state and cross-movie accuracies were the lowest. Results also showed that parcellation resolution and the number of volumes used in each matrix affect fingerprinting accuracies. Next, we calculated three measures of whole-connectome stability for each subject: cross-rest (Rest1-Rest2), cross-state (MovieDM-Rest1), and cross-movie (MovieDM-MovieTP), and three measures of within-state between-subject connectome similarity for Rest1, MovieDM, and MovieTP. We show that stability and similarity were correlated, but that these measures were not related to age. A principal component analysis of these measures yielded two components that we used to test for brain-behavior correlations with IQ, general psychopathology, and social skills measures (n = 119). The first component was significantly correlated with the social skills measure (r=-0.26, p = 0.005). Post hoc correlations showed that the social skills measure correlated with both cross-rest stability (r=-0.29, p = 0.001) and with connectome similarity during MovieDM (r=-0.28, p = 0.002). These findings suggest that the stability and similarity of the whole-brain connectome relate to the development of social skills. We infer that the maturation of the functional connectome simultaneously achieves patterns of FC that are distinct at the individual subject level, that are shared across individuals, and that are persistent across states and across runs-features which presumably combine to optimize neural processing during development. Future longitudinal work could reveal the developmental trajectories of stability and similarity of the connectome.

Neurocognitive risk markers in pediatric obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has complex genetic underpinnings, particularly in its early-onset form, which places siblings at a 10-fold increased risk of developing the disorder. Examination for neurocognitive markers preceding pediatric OCD onset has not been conducted, although markers have been identified in adult OCD. This study compared neurocognition across groups of OCD-affected youth (n = 87), unaffected siblings of those with early-onset OCD (n = 67), and healthy controls (HC; n = 79). METHODS: A total of 233 participants aged 6-18 years old completed standardized neurocognitive tests of cognitive flexibility, decision making, planning, response inhibition, spatial working memory, attention, recognition nonverbal memory, and intelligence. They were administered the Anxiety Disorders Interview Schedule-Parent version (ADIS-P) and completed self-report anxiety and OCD questionnaires. Linear mixed-effects models tested for differences between groups, adjusting for age, gender, IQ, state anxiety, and ethnicity, and accounting for random effects of family membership. RESULTS: OCD-affected youth and unaffected siblings performed significantly worse on planning in comparison to HCs (Cohen's d = 0.74; 95% CI = [0.11, 1.36]; Cohen's d = 0.75; 95% CI = [0.12, 1.38], respectively; omnibus group effect p = .007). No other significant between-group differences were identified. CONCLUSIONS: Neurocognitive performance differences between groups identified planning as a preexisting trait marker of pediatric OCD, while no other domain presented as a marker of pediatric OCD. This differs from adult OCD, which is associated with broader cognitive impairments. Investigating longitudinal trajectories and predictive significance of neurocognition in those affected by, and at risk for, early-onset OCD is warranted. Ideally, this will enhance individualized risk stratification and inform future prevention and early intervention strategies.

Functional brain networks involved in lexical decision.

Functional magnetic resonance imaging (fMRI)5 studies on lexical decision (LD)6 attempting to isolate the brain network underlying access to lexical representations can be confounded by attentional and response processes. However, manipulating the "wordlikeness" of the LD stimuli can facilitate functional interpretation of each emerging brain network, providing principles for separation of attentional demand from linguistic processing. This is because activation of difficult-to-access lexical representations (for obscure real words), and avoidance of interfering word properties (for wordlike non-words), are both generally attentionally demanding. Therefore, congruent patterns of activation would be predicted for general-attention-responsive networks, but opposing patterns for language-responsive networks. 59 healthy adults performed a LD task, and multidimensional functional connectivity analysis was used to extract three functional brain networks. A linguistic processing network (LPN) was separated from attention/response networks anatomically (LPN included Broca's and Wernicke's areas), but also temporally by showing reduced activation for the most attentionally demanding condition (i.e., wordlike non-words). This demonstrated that during LD in fMRI a network involved in linguistic processing can be disentangled from attention- and response-specific networks, using a combination of experimental design and multidimensional analysis methods.

Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study.

Hypercoupling of activity in speech-perception-specific brain networks has been proposed to play a role in the generation of auditory-verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task-based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI-CPCA), which allowed for comparison of task-related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory-motor, (b) language processing, and (c) default-mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory-motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non-AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech-perception-related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation.

Altered maternal immune networks are associated with adverse child neurodevelopment: Impact of alcohol consumption during pregnancy.

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-É£, IL-10, TNF-ß, TNF-α, and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.

Symptom-related attributional biases in schizophrenia and bipolar disorder.

INTRODUCTION: Biases in causal attributions and evidence integration have been implicated in delusions, but have not been investigated simultaneously to examine additive or multiplicative effects. It was hypothesised that paranoid delusions would correlate with self-serving and personalising biases ("defence" model of paranoia), particularly when these biases were disconfirmed. METHODS: Constrained principal component analysis was used to investigate differences between schizophrenia patients (paranoid vs. non-paranoid), bipolar disorder patients, and healthy controls, as well as to examine the extent to which psychotic symptoms could predict patterns of responding on a novel attributional bias task (Attributional Style BADE, or ASB) that requires integrating contextual information. RESULTS: Although no group differences were found, disorganisation and manic symptoms correlated with situation attributions and self-blame when such attributions were unsupported by the available evidence, and depression and anxiety correlated with other-person and self attributions (not situation attributions) when confirmed by the available evidence, regardless of diagnosis. CONCLUSIONS: While group differences accounted for little variance in responses on the ASB task, a transdiagnostic association between symptoms of psychosis and the ASB task was observed. This highlights the importance of considering symptom profiles rather than diagnostic groupings when investigating cognitive biases and related non-pharmacological treatments.

Impairment in subcortical suppression in schizophrenia: Evidence from the fBIRN Oddball Task.

Schizophrenia patients show widespread impairments in brain activity during oddball tasks, which involve responding to infrequent target stimuli while refraining from responding during continuous non-target stimuli. In a network-based investigation comparing schizophrenia or schizoaffective patients to healthy controls, we sought to clarify which networks were specifically associated with target detection using a multivariate analysis technique that identifies task-specific functional brain networks. We acquired data from the publicly available function biomedical informatics research network collaboration, including 58 patients and 50 controls. Two task-based functional brain networks were identified: (1) a response modulation network including bilateral temporal pole, supramarginal gyrus, striatum, and thalamus, on which patients showed decreased activity relative to controls; and (2) an auditory-motor response activation network, on which patients showed a slower return to baseline than controls, but no difference in peak activation. For both groups, baseline to peak activation of the response modulation network correlated negatively with peak to baseline activity in the response activation network, suggesting a role in suppressing the motor response following targets. Patients' impaired activity in the response modulation network, and subsequent longer return to baseline in the response activation network, correspond with their later and less accurate behavioral performance, suggesting that impairment in suppression of the auditory-motor response activation network could underlie oddball task deficits in schizophrenia. In addition, the magnitude of the activity in the response modulation network was correlated with intensity of delusions of reference, supporting the notion that increased referential ideation is associated with hyperactivity within the subcortical striatal-limbic network. Hum Brain Mapp 37:4640-4653, 2016. © 2016 Wiley Periodicals, Inc.

Overconfidence across the psychosis continuum: a calibration approach.

INTRODUCTION: An 'overconfidence in errors' bias has been consistently observed in people with schizophrenia relative to healthy controls, however, the bias is seldom found to be associated with delusional ideation. Using a more precise confidence-accuracy calibration measure of overconfidence, the present study aimed to explore whether the overconfidence bias is greater in people with higher delusional ideation. METHODS: A sample of 25 participants with schizophrenia and 50 non-clinical controls (25 high- and 25 low-delusion-prone) completed 30 difficult trivia questions (accuracy <75%); 15 'half-scale' items required participants to indicate their level of confidence for accuracy, and the remaining 'confidence-range' items asked participants to provide lower/upper bounds in which they were 80% confident the true answer lay within. RESULTS: There was a trend towards higher overconfidence for half-scale items in the schizophrenia and high-delusion-prone groups, which reached statistical significance for confidence-range items. However, accuracy was particularly low in the two delusional groups and a significant negative correlation between clinical delusional scores and overconfidence was observed for half-scale items within the schizophrenia group. Evidence in support of an association between overconfidence and delusional ideation was therefore mixed. CONCLUSIONS: Inflated confidence-accuracy miscalibration for the two delusional groups may be better explained by their greater unawareness of their underperformance, rather than representing genuinely inflated overconfidence in errors.

Functional brain networks underlying detection and integration of disconfirmatory evidence.

Processing evidence that disconfirms a prior interpretation is a fundamental aspect of belief revision, and has clear social and clinical relevance. This complex cognitive process requires (at minimum) an alerting stage and an integration stage, and in the current functional magnetic resonance imaging (fMRI) study, we used multivariate analysis methodology on two datasets in an attempt to separate these sequentially-activated cognitive stages and link them to distinct functional brain networks. Thirty-nine healthy participants completed one of two versions of an evidence integration experiment involving rating two consecutive animal images, both of which consisted of two intact images of animal faces morphed together at different ratios (e.g., 70/30 bird/dolphin followed by 10/90 bird/dolphin). The two versions of the experiment differed primarily in terms of stimulus presentation and timing, which facilitated functional interpretation of brain networks based on differences in the hemodynamic response shapes between versions. The data were analyzed using constrained principal component analysis for fMRI (fMRI-CPCA), which allows distinct, simultaneously active task-based networks to be separated, and these were interpreted using both temporal (task-based hemodynamic response shapes) and spatial (dominant brain regions) information. Three networks showed increased activity during integration of disconfirmatory relative to confirmatory evidence: (1) a network involved in alerting to the requirement to revise an interpretation, identified as the salience network (dorsal anterior cingulate cortex and bilateral insula); (2) a sensorimotor response-related network (pre- and post-central gyri, supplementary motor area, and thalamus); and (3) an integration network involving rostral prefrontal, orbitofrontal and posterior parietal cortex. These three networks were staggered in their peak activity (alerting, responding, then integrating), but at certain time points (e.g., 17s after trial onset) the hemodynamic responses associated with all three networks were simultaneously active. These findings highlight distinct cognitive processes and corresponding functional brain networks underlying stages of disconfirmatory evidence integration, and demonstrate the power of multivariate and multi-experiment methodology in cognitive neuroscience.

Reduced functional connectivity during controlled semantic integration in schizophrenia: A multivariate approach.

Impairment in controlled semantic association is a central feature of schizophrenia, and the goal of the current functional magnetic resonance imaging study was to identify the neural correlates of this impairment. Thirty people with schizophrenia and 30 healthy age- and gender-matched control subjects performed a task requiring participants to match word pairs that varied in semantic distance (distant vs. close). A whole-brain multivariate connectivity analysis revealed three functional brain networks of primary interest engaged by the task: two configurations of a multiple demands network, in which brain activity did not differ between groups, and a semantic integration network, in which coordinated activity was reduced in schizophrenia patients relative to healthy controls, for distantly relative to closely related word pairs. The hypoactivity during controlled semantic integration in schizophrenia reported here, combined with hyperactivity in automatic semantic association reported in the literature, suggests an imbalance between controlled integration and automatic association. This provides a biological basis for Bleuler's concept of schizophrenia as a "split mind" arising from an impaired ability to form coherent associations between semantic concepts.

Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in refractory psychosis.

Refractory psychosis units currently have little information regarding which symptoms profiles should be expected to respond to treatment. In the current study, we provide this information using structural equation modeling of Positive and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a sample of 610 patients admitted to a treatment refractory psychosis program at a Canadian tertiary care unit between 1990 and 2011. The hypothesized five-dimensional structure of the PANSS fit the data well at both admission and discharge, and the latent variable scores are reported as a function of symptom dimension and diagnostic category. The results suggest that, overall, positive symptoms (POS) responded to treatment better than all other symptoms dimensions, but for the schizoaffective and bipolar groups, greater response on POS was observed relative to the schizophrenia and major depression groups. The major depression group showed the most improvement on negative symptoms and emotional distress, and the bipolar group showed the most improvement on disorganization. Schizophrenia was distinct from schizoaffective disorder in showing reduced treatment response on all symptom dimensions. These results can assist refractory psychosis units by providing information on how PANSS symptom dimensions respond to treatment and how this depends on diagnostic category.

Action and outcome activity state patterns in the anterior cingulate cortex.

Although there are numerous theories regarding anterior cingulate cortex (ACC) function, most suggest that it is involved in some form of action or outcome processing. The present study characterized the dominant patterns of ACC activity on a task in which actions and outcomes could vary independently. Patterns of activity were detected using a modified form of principal component analysis (PCA), termed constrained PCA in which a regression procedure was applied prior to PCA to eliminate the contribution of nontask-related activity. When trials were grouped according to outcome, a PC was found in all subjects and sessions that had large fluctuations during actions but only differentiated correct versus error trials prior to the end of the delay and again at time of the outcome. Another PC was always present that separated right from left lever presses, but only around the time of the actual lever press. Individual neurons exhibited significant selectivities for trials involving different actions and/or outcomes. Of the ACC neurons that exhibited significant outcome selectivity, the majority fired more on error trials. The present study revealed separate as well as integrated action and outcome monitoring in the ACC, especially, although not exclusively, under conditions when an error is likely.

Metacognitive training for patients with schizophrenia: preliminary evidence for a targeted, single-module programme.

OBJECTIVE: Metacognitive training is an eight-module, group-based treatment programme for people with schizophrenia that targets the cognitive biases (i.e. problematic thinking styles) thought to contribute to the genesis and maintenance of delusions. The present article is an investigation into the efficacy of a shorter, more targeted, single-module metacognitive training programme, administered individually, which focuses specifically on improving cognitive biases that are thought to be driven by a 'hypersalience of evidence-hypothesis matches' mechanism (e.g. jumping to conclusions, belief inflexibility, reasoning heuristics, illusions of control). It was hypothesised that a more targeted metacognitive training module could still improve performance on these bias tasks and reduce delusional ideation, while improving insight and quality of life. METHOD: A sample of 28 patients diagnosed with schizophrenia and mild delusions either participated in the hour-long, single-session, targeted metacognitive training programme (n = 14), or continued treatment as usual (n = 14). All patients were assessed using clinical measures gauging overall positive symptomology, delusional ideation, quality of life and insight, and completed two cognitive bias tasks designed to elucidate the representativeness and illusion of control biases. RESULTS: After a 2-week, post-treatment interval, targeted metacognitive training patients exhibited significant decreases in delusional severity and conviction, significantly improved clinical insight, and significant improvements on the cognitive bias tasks, relative to the treatment-as-usual controls. Performance improvements on the cognitive bias tasks significantly correlated with the observed reductions in overall positive symptomology. Patients also evaluated the training positively. CONCLUSIONS: Although interpretations of these results are limited due to the lack of an optimally designed, randomised controlled trial and a small sample size, the results are promising and warrant further investigation into targeted versions of the metacognitive training programme.

Soundless voices, silenced selves: are auditory verbal hallucinations in schizophrenia truly perceptual?

In much contemporary psychiatric training and practice, there is a strong emphasis on the audible or perceptual quality and externality of auditory verbal hallucinations in clinical assessments. A typical question during clinical assessment is asking whether the voices that a person hears sound identical to the way the clinician's voice is heard. In this Personal View, we argue that the most important factor in auditory verbal hallucinations in schizophrenia spectrum psychoses is a loss of first-person authority, and that a perceptual quality is not required for it to be this kind of hallucination. We draw on evidence from cognitive neuroscience showing that the activation of brain networks retrieved during capture of auditory verbal hallucinations that were experienced when a patient was in a functional MRI scanner does not match activation of networks retrieved during auditory perception. We propose that, despite early writings by Esquirol and Schneider that defined auditory verbal hallucinations as beliefs in perception rather than true perception, cognitive neuroscience, psychiatric training and practice, and patients adopting clinical vocabulary have been strongly influenced by the progression of the diagnostic criteria for schizophrenia, which increasingly place emphasis on language, such as the "full force" of a true perception. We hold that this change has resulted in an unhelpful top-down influence on the field, imposing perceptual qualities on auditory verbal hallucinations, and leading to misunderstandings and inaccuracies in clinical practice and patients' self-reports, and misinterpretations in cognitive neuroscience. We encourage a revision of the definition of auditory verbal hallucinations to move away from the necessity for auditory perception, and towards beliefs in perception due to the loss of first-person authority.

Hypoactivation of the language network during auditory imagery contributes to hallucinations in Schizophrenia.

Auditory verbal hallucinations (AVHs) involve perceptions, often voices, in the absence of external stimuli, and rank among the most common symptoms of schizophrenia. Metrical stress evaluation requires determination of the stronger syllable in words, and therefore requires auditory imagery, of interest for investigation of hallucinations in schizophrenia. The current functional magnetic resonance imaging study provides an updated whole-brain network analysis of a previously published study on metrical stress, which showed reduced directed connections between Broca's and Wernicke's regions of interest (ROIs) for hallucinations. Three functional brain networks were extracted, with the language network (LN) showing an earlier and shallower blood-oxygen-level dependent (BOLD) response for hallucinating patients, in the auditory imagery condition only (the reduced activation for hallucinations observed in the original ROI-based results were not specific to the imagery condition). This suggests that hypoactivation of the LN during internal auditory imagery may contribute to the propensity to hallucinate. This accords with cognitive accounts holding that an impaired balance between internal and external linguistic processes (underactivity in networks involved in internal auditory imagery and overactivity in networks involved in speech perception) contributes to our understanding of the biological underpinnings of hallucinations.

Overlap between individual differences in cognition and symptoms of schizophrenia.

BACKGROUND: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. STUDY DESIGN: We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. CONCLUSIONS: The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

Epoch-specific functional networks involved in working memory.

Working memory (WM) is not a unitary construct. There are distinct processes involved in encoding information, maintaining it on-line, and using it to guide responses. The anatomical configurations of these processes are more accurately analyzed as functionally connected networks than collections of individual regions. In the current study we analyzed event-related functional magnetic resonance imaging (fMRI) data from a Sternberg Item Recognition Paradigm WM task using a multivariate analysis method that allowed the linking of functional networks to temporally-separated WM epochs. The length of the delay epochs was varied to optimize isolation of the hemodynamic response (HDR) for each task epoch. All extracted functional networks displayed statistically significant sensitivity to delay length. Novel information extracted from these networks that was not apparent in the univariate analysis of these data included involvement of the hippocampus in encoding/probe, and decreases in BOLD signal in the superior temporal gyrus (STG), along with default-mode regions, during encoding/delay. The bilateral hippocampal activity during encoding/delay fits with theoretical models of WM in which memoranda held across the short term are activated long-term memory representations. The BOLD signal decreases in the STG were unexpected, and may reflect repetition suppression effects invoked by internal repetition of letter stimuli. Thus, analysis methods focusing on how network dynamics relate to experimental conditions allowed extraction of novel information not apparent in univariate analyses, and are particularly recommended for WM experiments for which task epochs cannot be randomized.