Comparing the functional neuroanatomy of proactive and reactive control between patients with schizophrenia and healthy controls.

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Evidence for functional improvement in reward anticipation in recent onset schizophrenia after one year of coordinated specialty care.

BACKGROUND: Motivational impairment associated with deficits in processing the anticipation of future reward is hypothesized to be a cardinal feature of schizophrenia spectrum disorders (SZ). Evidence from short-term follow-up (6-week post-treatment) studies suggests that these deficits may improve or be reversed with treatment, although longer-term outcomes are unknown. Here we examined the one-year trajectory of functional activation in brain circuitry associated with reward anticipation in people with recent onset SZ who participated in coordinated specialty care (CSC) treatment, hypothesizing normalization of brain response mirroring previous short-term findings in first-episode individuals. METHOD: Blood oxygen level-dependent (BOLD) response in the dorsal anterior cingulate cortex, anterior insula, and ventral striatum (VS) associated with reward anticipation during the Incentivized Control Engagement Task (ICE-T) was analyzed in a baseline sample of 49 healthy controls (HCs) and 52 demographically matched people with SZ, with follow-up data available for 35 HCs and 17 people with SZ. RESULTS: In agreement with our hypothesis, significant time × diagnosis interactions were observed across all regions, in which reward anticipation-associated BOLD response increased in SZ to above baseline HC levels at follow-up. Increased VS activation was associated with decreased reality distortion symptoms over the follow-up period. Baseline reward anticipation-associated BOLD response in the right anterior insula was associated with improvement in reality distortion symptoms. CONCLUSIONS: These findings suggest that functional deficits in reward anticipation may be reversed after one year of CSC in recent onset participants with SZ, and that this improvement is associated with reduced positive symptoms in the illness.

Both unmedicated and medicated individuals with schizophrenia show impairments across a wide array of cognitive and reinforcement learning tasks.

BACKGROUND: Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function. METHODS: The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning. RESULTS: Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks. CONCLUSIONS: These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.

Task-specific Disruptions in Theta Oscillations during Working Memory for Temporal Order in People with Schizophrenia.

Prior studies demonstrated that neural oscillations are enhanced during working memory (WM) maintenance and that this activity can predict behavioral performance in healthy individuals. However, it is unclear whether the relationship holds for people with WM deficits. People with schizophrenia have marked WM deficits, and such deficits are most prominent when patients are required to process relationships between items, such as temporal order. Here, we used EEG to compare the relationship between oscillatory activity and WM performance in patients and controls. EEG was recorded as participants performed tasks requiring maintenance of complex objects ("Item") or the temporal order of objects ("Order"). In addition to testing for group differences, we examined individual differences in EEG power and WM performance across groups. Behavioral results demonstrated that patients showed impaired performance on both Item and Order trials. EEG analyses revealed that patients showed an overall reduction in alpha power, but the relationship between alpha activity and performance was preserved. In contrast, patients showed a reduction in theta power specific to Order trials, and theta power could predict performance on Order trials in controls, but not in patients. These findings demonstrate that WM impairments in patients may reflect two different processes: a general deficit in alpha oscillations and a specific deficit in theta oscillations when temporal order information must be maintained. At a broader level, the results highlight the value of characterizing brain-behavior relationships, by demonstrating that the relationship between neural oscillations and WM performance can be fundamentally disrupted in those with WM deficits.

Dynamic reorganization of the frontal parietal network during cognitive control and episodic memory.

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamically and can be represented as functional connectivity changes between network elements. Using graph theory, we explored context-dependent network reorganization in 56 healthy adults performing fMRI tasks from two cognitive domains that varied in CC and episodic-memory demands. We examined whole-brain modular structure during the DPX task, which engages proactive CC in the frontal-parietal cognitive-control network (FPN), and the RiSE task, which manipulates CC demands at encoding and retrieval during episodic-memory processing, and engages FPN, the medial-temporal lobe and other memory-related networks in a context dependent manner. Analyses revealed different levels of network integration and segregation. Modularity analyses revealed greater brain-wide integration across tasks in high CC conditions compared to low CC conditions. Greater network reorganization occurred in the RiSE memory task, which is thought to require coordination across multiple brain networks, than in the DPX cognitive-control task. Finally, FPN, ventral attention, and visual systems showed within network connectivity effects of cognitive control; however, these cognitive systems displayed varying levels of network reorganization. These findings provide insight into how brain networks reorganize to support differing task contexts, suggesting that the FPN flexibly segregates during focused proactive control and integrates to support control in other domains such as episodic memory.

Predicting psychosis risk using a specific measure of cognitive control: a 12-month longitudinal study.

BACKGROUND: Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up. METHODS: Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models. RESULTS: Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups. CONCLUSIONS: These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.

The Hippocampus Generalizes across Memories that Share Item and Context Information.

Episodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. One major area of debate hinges on a discrepancy between two hypothesized roles of the hippocampus: differentiating between similar events to reduce interference and assigning similar representations to events that share overlapping items and contextual information. Here, we used multivariate analyses of activity patterns measured with fMRI to characterize how the hippocampus distinguishes between memories based on similarity at the level of items and/or context. Hippocampal activity patterns discriminated between events that shared either item or context information but generalized across events that shared similar item-context associations. The current findings provide evidence that, whereas the hippocampus can reduce mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item-context relations. This lends new insights into the way the hippocampus may balance multiple mnemonic operations in adaptively guiding behavior.

Adaptive task difficulty influences neural plasticity and transfer of training.

The efficacy of cognitive training is controversial, and research progress in the field requires an understanding of factors that promote transfer of training gains and their relationship to changes in brain activity. One such factor may be adaptive task difficulty, as adaptivity is predicted to facilitate more efficient processing by creating a prolonged mismatch between the supply of, and the demand upon, neural resources. To test this hypothesis, we measured behavioral and neural plasticity in fMRI sessions before and after 10 sessions of working memory updating (WMU) training, in which the difficulty of practiced tasks either adaptively increased in response to performance or was fixed. Adaptive training resulted in transfer to an untrained episodic memory task and activation decreases in striatum and hippocampus on a trained WMU task, and the amount of training task improvement was associated with near transfer to other WMU tasks and with hippocampal activation changes on both near and far transfer tasks. These findings suggest that cognitive training programs should incorporate adaptive task difficulty to broaden transfer of training gains and maximize efficiency of task-related brain activity.

Electrophysiological Evidence for Impaired Control of Motor Output in Schizophrenia.

Previous research has demonstrated pervasive deficits in response-related processing in people with schizophrenia (PSZ). The present study used behavioral measures and event-related potentials (ERPs) to test the hypothesis that schizophrenia involves specific impairment in the ability to exert control over response-related processing. Twenty-two PSZ and 22 matched control participants completed a choice response task in counterbalanced testing sessions that emphasized only accuracy (the unspeeded condition) or emphasized speed and accuracy equally (the speeded condition). Control participants successfully modulated behavioral and ERP indices of response-related processing under speed pressure, as evidenced by faster and less variable reaction times (RTs) and an earlier onset and increased amplitude lateralized readiness potential (LRP). By contrast, PSZ were unable to improve RT speed or variability or to modulate the LRP under speed pressure, despite showing a decrease in accuracy. Notably, response-related deficits in PSZ emerged only in the speeded condition; behavioral and ERP measures did not differ between groups in the unspeeded condition. Together, these results indicate that impairment in the ability to exert control over response-related processing may underlie response-related deficits in schizophrenia.

The neural circuitry supporting goal maintenance during cognitive control: a comparison of expectancy AX-CPT and dot probe expectancy paradigms.

Goal maintenance is an aspect of cognitive control that has been identified as critical for understanding psychopathology according to criteria of the NIMH-sponsored CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) and Research Domain Criteria (RDoC) initiatives. CNTRICS proposed the expectancy AX-CPT, and its visual-spatial parallel the dot probe expectancy (DPX), as valid measures of the cognitive and neural processes thought to be relevant for goal maintenance. The goal of this study was to specifically examine the functional neural correlates and connectivity patterns of both goal maintenance tasks in the same subset of subjects to further validate their neural construct validity and clarify our understanding of the nature and function of the neural circuitry engaged by the tasks. Twenty-six healthy control subjects performed both the letter (AX) and dot pattern (DPX) variants of the CPT during fMRI. Behavioral performance was similar between tasks. The 2 tasks engaged the same brain networks including dorsolateral prefrontal cortex (DLPFC) and dorsal parietal regions, supporting their validity as complementary measures of the goal maintenance construct. Interestingly there was greater engagement of the frontal opercular insula region during the expectancy AX-CPT (letter) and greater functional connectivity between the PFC and medial temporal lobe in the DPX (dot pattern). These differences are consistent with differential recruitment of phonological and visual-spatial processes by the two tasks and suggest that additional long-term memory systems may be engaged by the dot probe version.

The Relational and Item-Specific Encoding Task in Mild Cognitive Impairment and Alzheimer Disease.

BACKGROUND: The Relational and Item-Specific Encoding task (RISE) measures episodic memory subcomponents, including item-specific and relational encoding of to-be-remembered stimuli. These memory components are neurobiologically relevant because they may engage distinct subregions of the medial temporal lobe, perirhinal and entorhinal cortices, parahippocampus, and hippocampus. METHODS: A total of 125 participants, including 84 healthy controls (HC), 22 mild cognitive impairment-diagnosed and 19 Alzheimer disease (AD)-diagnosed participants, were administered the RISE and neuropsychological measures. Stepwise linear regressions assessed prediction of functional ability from RISE d' measures. ANOVAs and logistic regressions determined the ability of the RISE to discriminate between the diagnostic groups. In addition, the psychometric properties of the RISE were examined. RESULTS: RISE measures predicted diagnosis with pseudo R2 values in the range of 0.25-0.30. Receiver operating characteristic curves demonstrated adequate sensitivity and specificity with areas under the curve in the range of 0.78-0.98. Memory following relational encoding was a significant predictor of everyday functional competence. The RISE had acceptable psychometric properties, with the exception of floor effects in the AD group. CONCLUSION: The RISE measures significantly predicted diagnosis and predicted everyday functional competence. The RISE offers unique advantages in the assessment of HC and individuals with preclinical AD.

Spared and impaired spoken discourse processing in schizophrenia: effects of local and global language context.

Individuals with schizophrenia are impaired in a broad range of cognitive functions, including impairments in the controlled maintenance of context-relevant information. In this study, we used ERPs in human subjects to examine whether impairments in the controlled maintenance of spoken discourse context in schizophrenia lead to overreliance on local associations among the meanings of individual words. Healthy controls (n = 22) and patients (n = 22) listened to short stories in which we manipulated global discourse congruence and local priming. The target word in the last sentence of each story was globally congruent or incongruent and locally associated or unassociated. ERP local association effects did not significantly differ between control participants and schizophrenia patients. However, in contrast to controls, patients only showed effects of discourse congruence when targets were primed by a word in the local context. When patients had to use discourse context in the absence of local priming, they showed impaired brain responses to the target. Our findings indicate that schizophrenia patients are impaired during discourse comprehension when demands on controlled maintenance of context are high. We further found that ERP measures of increased reliance on local priming predicted reduced social functioning, suggesting that alterations in the neural mechanisms underlying discourse comprehension have functional consequences in the illness.

Brain mechanisms of successful recognition through retrieval of semantic context.

Episodic memory is associated with the encoding and retrieval of context information and with a subjective sense of reexperiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a "general recollection network" including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In this study, we used fMRI to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context) or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently defined ROIs and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience.

Common and specific cognitive deficits in schizophrenia: relationships to function.

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.

A Transdiagnostic Study of Effort-Cost Decision-Making in Psychotic and Mood Disorders.

BACKGROUND: Research suggests that effort-cost decision-making (ECDM), the estimation of work required to obtain reward, may be a relevant framework for understanding motivational impairment in psychotic and mood pathology. Specifically, research has suggested that people with psychotic and mood pathology experience effort as more costly than controls, and thus pursue effortful goals less frequently. This study examined ECDM across psychotic and mood pathology. HYPOTHESIS: We hypothesized that patient groups would show reduced willingness to expend effort compared to controls. STUDY DESIGN: People with schizophrenia (N = 33), schizoaffective disorder (N = 28), bipolar disorder (N = 39), major depressive disorder (N = 40), and controls (N = 70) completed a physical ECDM task. Participants decided between completing a low-effort or high-effort option for small or larger rewards, respectively. Reward magnitude, reward probability, and effort magnitude varied trial-by-trial. Data were analyzed using standard and hierarchical logistic regression analyses to assess the subject-specific contribution of various factors to choice. Negative symptoms were measured with a clinician-rated interview. STUDY RESULTS: There was a significant effect of group, driven by reduced choice of high-effort options in schizophrenia. Hierarchical logistic regression revealed that reduced choice of high-effort options in schizophrenia was driven by weaker contributions of probability information. Use of reward information was inversely associated with motivational impairment in schizophrenia. Surprisingly, individuals with major depressive disorder and bipolar disorder did not differ from controls. CONCLUSIONS: Our results provide support for ECDM deficits in schizophrenia. Additionally, differences between groups in ECDM suggest a seemingly similar behavioral phenotype, reduced motivation, could arise from disparate mechanisms.

Assessing Trial-by-Trial Electrophysiological and Behavioral Markers of Attentional Control and Sensory Precision in Psychotic and Mood Disorders.

BACKGROUND AND HYPOTHESIS: The current study investigated the extent to which changes in attentional control contribute to performance on a visual perceptual discrimination task, on a trial-by-trial basis in a transdiagnostic clinical sample. STUDY DESIGN: Participants with schizophrenia (SZ; N = 58), bipolar disorder (N = 42), major depression disorder (N = 51), and psychiatrically healthy controls (N = 92) completed a visual perception task in which stimuli appeared briefly. The design allowed us to estimate the lapse rate and the precision of perceptual representations of the stimuli. Electroencephalograms (EEG) were recorded to examine pre-stimulus activity in the alpha band (8-13 Hz), overall and in relation to behavior performance on the task. STUDY RESULTS: We found that the attention lapse rate was elevated in the SZ group compared with all other groups. We also observed group differences in pre-stimulus alpha activity, with control participants showing the highest levels of pre-stimulus alpha when averaging across trials. However, trial-by-trial analyses showed within-participant fluctuations in pre-stimulus alpha activity significantly predicted the likelihood of making an error, in all groups. Interestingly, our analysis demonstrated that aperiodic contributions to the EEG signal (which affect power estimates across frequency bands) serve as a significant predictor of behavior as well. CONCLUSIONS: These results confirm the elevated attention lapse rate that has been observed in SZ, validate pre-stimulus EEG markers of attentional control and their use as a predictor of behavior on a trial-by-trial basis, and suggest that aperiodic contributions to the EEG signal are an important target for further research in this area, in addition to alpha-band activity.

The diagnostic accuracy of screening for psychosis spectrum disorders in behavioral health clinics integrated into primary care.

Screening for psychosis spectrum disorders in primary care could improve early identification and reduce the duration of untreated psychosis. However, the accuracy of psychosis screening in this setting is unknown. To address this, we conducted a diagnostic accuracy study of screening for psychosis spectrum disorders in eight behavioral health services integrated into primary care clinics. Patients attending an integrated behavioral health appointment at their primary care clinic completed the Prodromal Questionnaire - Brief (PQ-B) immediately prior to their intake assessment. This was compared to a diagnostic phone interview based on the Structured Interview for Psychosis Risk Syndromes (SIPS). In total, 145 participants completed all study procedures, of which 100 screened positive and 45 negative at a provisional PQ-B threshold of ≥20. The PQ-B was moderately accurate at differentiating psychosis spectrum from no psychosis spectrum disorders; a PQ-B distress score of ≥27 had a sensitivity and specificity of 71.2 % and 57.0 % respectively. In total, 66 individuals (45.5 %) met criteria for a psychosis spectrum disorder and 24 (16.7 %) were diagnosed with full psychosis, indicating a high prevalence of psychosis in the sample. Overall, screening for psychosis spectrum disorders in an IBH primary care setting identified a relatively high number of individuals and may identify people that would otherwise be missed. The PQ-B performed slightly less well than in population-based screening in community mental health settings. However, the findings suggest this may represent an effective way to streamline the pathway between specialty early psychosis programs and primary care clinics for those in need.

Differential connectivity of perirhinal and parahippocampal cortices within human hippocampal subregions revealed by high-resolution functional imaging.

Numerous studies support the importance of the perirhinal cortex (PRC) and parahippocampal cortex (PHC) in episodic memory. Theories of PRC and PHC function in humans have been informed by neuroanatomical studies of these regions obtained in animal tract-tracing studies, but knowledge of the connectivity of PHC and PRC in humans is limited. To address this issue, we used resting-state functional magnetic resonance imaging to compare the intrinsic functional connectivity profiles associated with the PRC and PHC both across the neocortex and within the subfields of the hippocampus. In Experiment 1, we acquired standard-resolution whole-brain resting-state fMRI data in 15 participants, and in Experiment 2, we acquired high-resolution resting-state fMRI data targeting the hippocampus in an independent sample of 15 participants. Experiment 1 revealed that PRC showed preferential connectivity with the anterior hippocampus, whereas PHC showed preferential connectivity with posterior hippocampus. Experiment 2 indicated that this anterior-posterior functional connectivity dissociation was more evident for subfields CA1 and subiculum than for a combined CA2/CA3/dentate gyrus region. Finally, whole-brain analyses from Experiment 1 revealed preferential PRC connectivity with an anterior temporal and frontal cortical network, and preferential PHC connectivity with a posterior medial temporal, parietal, and occipital network. These results suggest a framework for refining models of the functional organization of the human medial temporal lobes in which the PRC and PHC are associated with distinct neocortical pathways that, in turn, may differentially interact with regions along the anterior-posterior axis of the hippocampus.

Relational memory weakness in autism despite the use of a controlled encoding task.

Introduction: Recent work challenged past findings that documented relational memory impairments in autism. Previous studies often relied solely on explicit behavioral responses to assess relational memory integrity, but successful performance on behavioral tasks may rely on other cognitive abilities (e.g., executive functioning) that are impacted in some autistic individuals. Eye-tracking tasks do not require explicit behavioral responses, and, further, eye movements provide an indirect measure of memory. The current study examined whether memory-specific viewing patterns toward scenes differ between autistic and non-autistic individuals. Methods: Using a long-term memory paradigm that equated for complexity between item and relational memory tasks, participants studied a series of scenes. Following the initial study phase, scenes were re-presented, accompanied by an orienting question that directed participants to attend to either features of an item (i.e., in the item condition) or spatial relationships between items (i.e., in the relational condition) that might be subsequently modified during test. At test, participants viewed scenes that were unchanged (i.e., repeated from study), scenes that underwent an "item" modification (an exemplar switch) or a "relational" modification (a location switch), and scenes that had not been presented before. Eye movements were recorded throughout. Results: During study, there were no significant group differences in viewing directed to regions of scenes that might be manipulated at test, suggesting comparable processing of scene details during encoding. However, there was a group difference in explicit recognition accuracy for scenes that underwent a relational change. Marginal group differences in the expression of memory-based viewing effects during test for relational scenes were consistent with this behavioral outcome, particularly when analyses were limited to scenes recognized correctly with high confidence. Group differences were also evident in correlational analyses that examined the association between study phase viewing and recognition accuracy and between performance on the Picture Sequence Memory Test and recognition accuracy. Discussion: Together, our findings suggest differences in the integrity of relational memory representations and/or in the relationships between subcomponents of memory in autism.

Memory-Based Prediction Deficits and Dorsolateral Prefrontal Dysfunction in Schizophrenia.

BACKGROUND: Theories suggest that people with schizophrenia (SZ) have problems generating predictions based on past experiences. The dorsolateral prefrontal cortex (DLPFC) and hippocampus participate in memory-based prediction. We used functional magnetic resonance imaging to investigate DLPFC and hippocampal function in healthy control (HC) subjects and people with SZ during memory-based prediction. METHODS: Prior to scanning, HC subjects (n = 54) and people with SZ (n = 31) learned 5-object sequences presented in fixed or random orders on each repetition. During scanning, participants made semantic decisions (e.g., "Can this object fit in a shoebox?") on a continuous stream of objects from fixed and random sequences. Sequence prediction was demonstrated by faster semantic decisions for objects in fixed versus random sequences because memory could be used to anticipate and more efficiently process semantic information about upcoming objects in fixed sequences. Representational similarity analyses were used to determine how each sequence type was represented in the posterior hippocampus and DLPFC. RESULTS: Sequence predictions were reduced in individuals with SZ relative to HC subjects. Representational similarity analyses revealed stronger memory-based predictions in the DLPFC of HC subjects than people with SZ, and DLPFC representations correlated with more successful predictions in HC subjects only. For the posterior hippocampus, voxel pattern similarity was increased for fixed versus random sequences in HC subjects only, but no significant between-group differences or correlations with prediction success were observed. CONCLUSIONS: Individuals with SZ are capable of learning temporal sequences; however, they are impaired using memory to predict upcoming events as efficiently as HC subjects. This deficit appears related to disrupted neural representation of sequence information in the DLPFC.