Task-merging for finer separation of functional brain networks in working memory.

BACKGROUND: In task-state functional magnetic resonance imaging (fMRI), hemodynamic response (HDR) shapes help identify cognitive process(es) supported by a brain network. However, when distinguishable networks have similar time courses, the low temporal resolution of the HDRs may result in spatial and temporal blurring of these networks. The present study demonstrated how task-merging and multivariate analysis allows data-driven separation of working memory (WM) processes. This was achieved by combining a WM task with the Thought Generation Task (TGT), a task which also requires attention to internal representations but no overt behavioral response. METHODS: 69 adults completed one of two tasks: (1) a Sternberg WM task, whereby participants had to remember a string of letters over a 4-sec delay or no delay, and (2) the TGT task, whereby participants internally generated or listened to a function of an object. WM data were analyzed in isolation and then with the TGT data, using multi-experiment constrained principal component analysis for fMRI (fMRI-CPCA). The function of each network was interpreted by evaluating HDR shapes across conditions (within and between tasks). RESULTS: The multi-experiment analysis produced three WM networks involving frontoparietal connectivity; two of these were combined when the WM task was analyzed alone. Notably, one network exhibited HDRs consistent with volitional attention to internal representations in both tasks (i.e., strongest in WM trials with a maintenance phase and in TGT trials involving silent thought). This network was separated from visual attention and motor response networks in the multi-experiment analysis only. CONCLUSIONS: Task-merging and multivariate analysis allowed us to differentiate WM networks possibly underlying internal attention (maintenance), visual attention (encoding), and response processes. Further, it allowed postulation of the cognitive operations subserved by each network by providing HDR shapes. This approach facilitates characterization of network functions by allowing direct comparisons of activity across different cognitive domains.

Alternation between different types of evidence attenuates judgments of severity.

Most real-world judgments and decisions require the consideration of multiple types of evidence. For example, judging the severity of environmental damage, medical illness, or negative economic trends often involves tracking and integrating evidence from multiple sources (i.e. different natural disasters, physical symptoms, or financial indicators). We hypothesized that the requirement to track and integrate across distinct types of evidence would affect severity judgments of multifaceted problems, compared to simpler problems. To test this, we used scenarios depicting crop damage. Each scenario involved either two event types (i.e. mold damage and insect damage), or one event type. Participants judged the quality of the crop following each scenario. In Experiments 1 and 2, subjective judgments were attenuated if the scenario depicted multiple event types, relative to scenarios depicting single event types. This was evident as a shallower slope of subjective severity ratings, as a function of objectively quantifiable severity, for scenarios with multiple event types. In Experiment 3, we asked whether alternation between event types might contribute to this attenuation. Each scenario contained two event types, and the sequence of events either alternated frequently between types or was organized into two sequential groups. Subjective judgments were attenuated for scenarios with frequently alternating sequences. The results demonstrate that alternation between distinct event types attenuates subjective judgments of severity. This suggests that a requirement to integrate evidence across multiple sources places extra demands on the cognitive system, which reduces the perceived evidence strength.

Left-dominant temporal-frontal hypercoupling in schizophrenia patients with hallucinations during speech perception.

BACKGROUND: Task-based functional neuroimaging studies of schizophrenia have not yet replicated the increased coordinated hyperactivity in speech-related brain regions that is reported with symptom-capture and resting-state studies of hallucinations. This may be due to suboptimal selection of cognitive tasks. METHODS: In the current study, we used a task that allowed experimental manipulation of control over verbal material and compared brain activity between 23 schizophrenia patients (10 hallucinators, 13 nonhallucinators), 22 psychiatric (bipolar), and 27 healthy controls. Two conditions were presented, one involving inner verbal thought (in which control over verbal material was required) and another involving speech perception (SP; in which control verbal material was not required). RESULTS: A functional connectivity analysis resulted in a left-dominant temporal-frontal network that included speech-related auditory and motor regions and showed hypercoupling in past-week hallucinating schizophrenia patients (relative to nonhallucinating patients) during SP only. CONCLUSIONS: These findings replicate our previous work showing generalized speech-related functional network hypercoupling in schizophrenia during inner verbal thought and SP, but extend them by suggesting that hypercoupling is related to past-week hallucination severity scores during SP only, when control over verbal material is not required. This result opens the possibility that practicing control over inner verbal thought processes may decrease the likelihood or severity of hallucinations.

Functional connectivity in a frontoparietal network involving the dorsal anterior cingulate cortex underlies decisions to accept a hypothesis.

Optimally interpreting our situations and experiences frequently requires comparing the evidence supporting conflicting hypotheses and deciding which to accept. This decision is comparable to an "Aha!" moment reached during insightful problem solving. We used a probabilistic reasoning task to investigate the neural activity underlying these processes. Participants rated the probability that a given focal hypothesis, rather than its alternative, was true. Decisions to accept the focal hypothesis elicited a stronger signal than decisions to reject it in a network involving the dorsal anterior cingulate cortex (dACC) and functionally connected frontal, parietal, and occipital regions. Follow-up analyses suggested that this was not simply a higher overall level of activation within the dACC or other individual regions of the network, but reflected a stronger signal for the network as a whole. This result is discussed in terms of functional connectivity between the dACC and other brain regions as a possible mechanism for coherence between components of a mental representation.

Patterns of Cortical Oscillations Organize Neural Activity into Whole-Brain Functional Networks Evident in the fMRI BOLD Signal.

Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG/MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

Bias in favour of self-selected hypotheses is associated with delusion severity in schizophrenia.

INTRODUCTION: Delusions are typically characterised by idiosyncratic, self-generated explanations used to interpret events, as opposed to the culturally normative interpretations. Thus, a bias in favour of one's own hypotheses may be a fundamental aspect of delusions. METHODS: We tested this possibility in the current study by comparing judgements of self-selected hypotheses to judgements of externally selected ones in a probabilistic reasoning task. This allowed us to equate self- and externally selected hypotheses in terms of objectively quantifiable supporting evidence. It is normal to be biased in favour of self-selected hypotheses, but we expected this bias to be exacerbated in schizophrenia patients relative to healthy and psychiatric controls, and to be correlated with the severity of delusions in the schizophrenia sample. RESULTS: As expected, all groups showed the self-selection bias. Although this bias was not increased in schizophrenia patients relative to the control groups, it was significantly correlated with the severity of delusions in the schizophrenia sample. CONCLUSIONS: These results fit with an account holding that the hypersalience of an individual's own interpretations of events, relative to culturally normative interpretations, may manifest in a self-selection bias, contributing to the delusional state in schizophrenia.

The bivalency effect in task switching: event-related potentials.

During task switching, if we occasionally encounter stimuli that cue more than one task (i.e., bivalent stimuli), response slowing is observed on all univalent trials within that block, even when no features overlap with the bivalent stimuli. This observation is known as the bivalency effect. Previous fMRI work (Woodward et al., 2008) clearly suggests a role for the dorsal anterior cingulate cortex (dACC) in the bivalency effect, but the time course remains uncertain. Here, we present the first high-temporal resolution account for the bivalency effect using stimulus-locked event-related potentials. Participants alternated among three simple tasks in six experimental blocks, with bivalent stimuli appearing occasionally in bivalent blocks (blocks 2, 4, and 6). The increased reaction times for univalent stimuli in bivalent blocks demonstrate that these stimuli are being processed differently from univalent stimuli in purely univalent blocks. Frontal electrode sites captured significant amplitude differences associated with the bivalency effect within time windows 100-120 ms, 375-450 ms, and 500-550 ms, which may reflect additional extraction of visual features present in bivalent stimuli (100-120 ms) and suppression of processing carried over from irrelevant cues (375-450 ms and 500-550 ms). Our results support the fMRI findings and provide additional evidence for involvement of the dACC. Furthermore, the bivalency effect dissipated with extended practice both behaviorally and electrophysiologically. These findings are discussed in relation to the differential processing involved in a controlled response style.

Hyperintensity of functional networks involving voice-selective cortical regions during silent thought in schizophrenia.

An important aspect of schizophrenia symptomatology is inner-outer confusion, or blurring of ego boundaries, which is linked to symptoms such as hallucinations and Schneiderian delusions. Dysfunction in the cognitive processes involved in the generation of private thoughts may contribute to blurring of the ego boundaries through increased activation in functional networks including speech- and voice-selective cortical regions. In the present study, the neural underpinnings of silent verbal thought generation and speech perception were investigated using functional magnetic resonance imaging (fMRI). Functional connectivity analysis was performed using constrained principal component analysis for fMRI (fMRI-CPCA). Group differences were observable on two functional networks: one reflecting hyperactivity in speech- and voice-selective cortical regions (e.g., bilateral superior temporal gyri (STG)) during both speech perception and silent verbal thought generation, and another involving hyperactivity in a multiple demands (i.e., task-positive) network that included Wernicke's area, during silent verbal thought generation. This set of preliminary results suggests that hyperintensity of functional networks involving voice-selective cortical regions may contribute to the blurring of ego boundaries characteristic of schizophrenia.

Decreased efficiency of task-positive and task-negative networks during working memory in schizophrenia.

Working memory (WM) is one of the most impaired cognitive processes in schizophrenia. Functional magnetic resonance imaging (fMRI) studies in this area have typically found a reduction in information processing efficiency but have focused on the dorsolateral prefrontal cortex. In the current study using the Sternberg Item Recognition Test, we consider networks of regions supporting WM and measure the activation of functionally connected neural networks over different WM load conditions. We used constrained principal component analysis with a finite impulse response basis set to compare the estimated hemodynamic response associated with different WM load condition for 15 healthy control subjects and 15 schizophrenia patients. Three components emerged, reflecting activated (task-positive) and deactivated (task-negative or default-mode) neural networks. Two of the components (with both task-positive and task-negative aspects) were load dependent, were involved in encoding and delay phases (one exclusively encoding and the other both encoding and delay), and both showed evidence for decreased efficiency in patients. The results suggest that WM capacity is reached sooner for schizophrenia patients as the overt levels of WM load increase, to the point that further increases in overt memory load do not increase fMRI activation, and lead to performance impairments. These results are consistent with an account holding that patients show reduced efficiency in task-positive and task-negative networks during WM and also partially support the shifted inverted-U-shaped curve theory of the relationship between WM load and fMRI activation in schizophrenia.

Evidence affects hypothesis judgments more if accumulated gradually than if presented instantaneously.

In a hypothesis comparison task involving quantifiable evidence, we investigated whether judgments of relative probability were affected by gradual evidence accumulation and by making a series of revised ratings, rather than a single final one. Each trial of our task required participants to rate the probability that a focal hypothesis, rather than its alternative, was correct. We manipulated (1) the strength of evidence supporting the focal hypothesis, (2) the strength of evidence supporting its alternative, and (3) whether that evidence was presented in three sequential portions (gradually accumulated evidence condition) or, instead, was all presented instantaneously (control condition). In a second experiment, we also manipulated (4) the number of successive ratings made within a trial with gradually accumulated evidence. Regardless of how many ratings were made per trial, gradual evidence accumulation increased the effects of evidence strength on ratings of relative probability.

The contribution of hypersalience to the "jumping to conclusions" bias associated with delusions in schizophrenia.

BACKGROUND: Previous schizophrenia research involving the "beads task" has suggested an association between delusions and 2 reasoning biases: (1) "jumping to conclusions" (JTC), whereby early, resolute decisions are formed on the basis of little evidence and (2) over-adjustment of probability estimates following a single instance of disconfirmatory evidence. In the current study, we used a novel JTC-style paradigm to provide new information about a cognitive operation common to these 2 reasoning biases. METHODS: Using a task that required participants to rate the likelihood that a fisherman was catching a series of black or white fish from Lake A and not Lake B, and vice versa, we compared the responses of 4 groups (healthy, bipolar, nondelusional schizophrenia and delusional schizophrenia) when we manipulated 2 elements of the Bayesian formula: incoming data and prior odds. RESULTS: Regardless of our manipulations of the Bayesian formula, the delusional schizophrenia group gave significantly higher likelihood ratings for the lake that best matched the colour of the presented fish, but the ratings for the nonmatching lake did not differ from the other groups. LIMITATIONS: The limitations of this study include a small sample size for the group of severely delusional patients and a preponderance of men in the schizophrenia sample. CONCLUSION: Delusions in schizophrenia are associated with hypersalience of evidence-hypothesis matches but normal salience of nonmatches. When the colour of the incoming data is uniform (fish of only one colour), this manifests as JTC early in a series, and when the colour of incoming data varies (both black and white fish), this manifests as an overadjustment midseries. This account can provide a unifying explanation for delusion-associated performance patterns previously observed in the beads task in schizophrenia.

Inhibition of return in the covert deployment of attention: evidence from human electrophysiology.

People are slow to react to objects that appear at recently attended locations. This delay-known as inhibition of return (IOR)-is believed to aid search of the visual environment by discouraging inspection of recently inspected objects. However, after two decades of research, there is no evidence that IOR reflects an inhibition in the covert deployment of attention. Here, observers participated in a modified visual-search task that enabled us to measure IOR and an ERP component called the posterior contralateral N2 (N2pc) that reflects the covert deployment of attention. The N2pc was smaller when a target appeared at a recently attended location than when it appeared at a recently unattended location. This reduction was due to modulation of neural processing in the visual cortex and the right parietal lobe. Importantly, there was no evidence for a delay in the N2pc. We conclude that in our task, the inhibitory processes underlying IOR reduce the probability of shifting attention to recently attended locations but do not delay the covert deployment of attention itself.

Source monitoring biases and auditory hallucinations.

INTRODUCTION: Previous source monitoring studies on schizophrenia reported an association between external source misattribution and hallucinations, but this is often not replicated. This inconsistency may be attributable to a failure in accounting for guessing parameters when computing source monitoring biases. METHODS: Fifty-one patients and 20 healthy controls were required to recall the source of items originating from external (computer and experimenter) or internal (the subject) sources. When statistically determined criteria were met, the appropriate counts of false positives were entered as covariates in the statistical analyses (analysis of covariance; ANCOVA) to exclude guessing from source monitoring bias measures. RESULTS: When comparing patients to controls, impairments on item recognition and source discrimination were observed. When comparing patient groups split on hallucinations, a bias towards attributing self-generated items to an external source was observed. A group difference on the externalisation bias was absent when the sample was split on delusions. CONCLUSIONS: A bias towards attributing self-generated items to an external source was associated with hallucinations. This ANCOVA methodology is recommended for source monitoring studies investigating group differences, and suggests that previously reported null results may be attributable to a failure in separating guessing and source monitoring measures.

Increased hindsight bias in schizophrenia.

An underlying theme common to prominent theoretical accounts of cognition in schizophrenia is that information processing is disproportionately influenced by recently/currently encountered information relative to the influence of previously learned information. In this study, the authors tested this account by using the hindsight bias or knew-it-all-along (KIA) paradigm, which demonstrates that newly acquired knowledge influences recall of past events. In line with the account that patients with schizophrenia display a disproportionately strong influence of recently encountered information relative to the influence of previously learned information, patients displayed a KIA effect that was significantly greater than in controls. This result is discussed in the context of the cognitive underpinnings of the KIA effect and delusion formation.

The contribution of a cognitive bias against disconfirmatory evidence (BADE) to delusions in schizophrenia.

A neuropsychological paradigm is introduced that provides a measure of a bias against disconfirmatory evidence (BADE), and its correspondence with delusions in people with schizophrenia and schizoaffective disorder was investigated. Fifty-two patients diagnosed with schizophrenia or schizoaffective disorder (36 were acutely delusional) and 24 healthy control participants were presented with delusion-neutral pictures in each trial, and were asked to rate the plausibility of four written interpretations of the scenario depicted by that picture. Subsequently, new pictures that provided background information about the depicted scenario were successively presented, and participants were requested to adjust their ratings, taking into account this new information. Two of the interpretations appeared tenable initially but ultimately proved to be implausible, one appeared untenable initially but eventually proved to be plausible, and one appeared untenable at all stages. A BADE was observed for delusional compared to non-delusional patients, as well as for all patients compared to controls. In addition, regardless of symptom profile, patients were more accepting of implausible interpretations than controls. The present work suggests that deficits in reasoning may contribute to the maintenance of delusions via an impairment in the processing of disconfirmatory evidence.

Confidence in errors as a possible basis for delusions in schizophrenia.

In two previous studies, it was observed that schizophrenic patients display increased confidence in memory errors compared with controls. The patient group displayed an increased proportion of errors in their knowledge system, quantified as the percentage of high-confident responses that are errors. The latter phenomenon has been termed knowledge corruption and is put forward as a risk factor for the emergence of delusions. In the present study, knowledge corruption was analyzed separately for different aspects of memory errors. A source-monitoring task was used, for which participants (30 schizophrenic patients with past or current paranoid ideas and 15 healthy controls) were asked to provide associates for each of 20 prime words. Later, participants were required to recognize studied words among distractor words, judge the original source, and provide a confidence rating for the most recent decision. Schizophrenic patients displayed greater confidence in memory errors compared with controls. Knowledge corruption was observed to be significantly greater in schizophrenic patients relative to controls for false-positive and false-negative judgments. It is proposed that reliance on false knowledge represents a candidate mechanism for the emergence of fixed false beliefs (i.e., delusions).

Visual search irregularities in schizophrenia depend on display size switching.

INTRODUCTION: In past research it has been demonstrated that when performing a visual search task with either one or multiple (4, 7 or 10) stimuli displayed, patients with schizophrenia demonstrate slow response times (RTs) in the display size of one, target-absent (one-absent) condition. The goals of the present investigation were to replicate this effect, and to gain an understanding of the underlying cognitive operations by comparing display-size switch to display-size repeat trials. METHODS: In two experiments, patients and controls performed a visual search task with either one or four stimuli displayed. In Experiment 1 (one block with mixed switch and repeat trials), RT for display-size switch trials was compared to RT from display-size repeat trials. In Experiment 2, the display-size one and display-size four conditions were run in separate, homogeneous blocks. RESULTS: The results demonstrate that the one-absent slowing effect was eliminated on repeat trials, regardless of whether the switch and repeat trials were mixed or presented in separate blocks. CONCLUSIONS: This set of results suggests that a combination of cueing and switching effects may underlie the one-absent slowing observed in patients, such that switching to the one-absent condition is difficult due to insufficient cueing of the relevant cognitive operations. This visual search paradigm is an excellent candidate for inclusion in the development of a neurocognitive profile specific to schizophrenia.

False memories in schizophrenia.

In prior studies, it was observed that patients with schizophrenia show abnormally high knowledge corruption (i.e., high-confident errors expressed as a percentage of all high-confident responses were increased for schizophrenic patients relative to controls). The authors examined the conditions under which excessive knowledge corruption occurred using the Deese-Roediger-McDermott paradigm. Whereas knowledge corruption in schizophrenia was significantly greater for false-negative errors relative to controls, no group difference occurred for false-positive errors. The groups showed a comparable high degree of confidence for false-positive recognition of critical lure items. Similar to findings collected in elderly participants, patients, but not controls, showed a strong positive correlation between the number of recognized studied items and false-positive recognition of the critical lure.