Setting the beat of an internal clock: Effects of dexamphetamine on different interval ranges of temporal processing in healthy volunteers.

Drug studies are powerful models to investigate the neuropharmacological mechanisms underlying temporal processing in humans. This study administered dexamphetamine to 24 healthy volunteers to investigate time perception at different time scales, along with contributions from working memory. Healthy volunteers were administered 0.45 mg/kg dexamphetamine or placebo in a double-blind, crossover, placebo-controlled design. Time perception was assessed using three experimental tasks: a time-discrimination task, which asked participants to determine whether a comparison interval (1200 ± 0, 50, 100, 150, 200 ms) was shorter or longer than a standard interval (1200 ms); a retrospective time estimation task, which required participants to verbally estimate time intervals (10, 30, 60, 90 and 120 s) retrospectively; and a prospective time-production task, where participants were required to prospectively monitor the passing of time (10, 30, 60, 90 and 120 s). Working memory was assessed with the backwards digit span. On the discrimination task, there was a change in the proportion of long-to-short responses and reaction times in the dexamphetamine condition (but no association with working memory), consistent with an increase in the speed of an internal pacemaker, and an overestimation of durations in the timing of shorter intervals. There was an interaction between dexamphetamine, working memory, and performance on the estimation and production tasks, whereby increasing digit span scores were associated with decreasing interval estimates and increased produced intervals in the placebo condition, but were associated with increased interval estimates and decreased produced intervals after dexamphetamine administration. These findings indicate that the dexamphetamine-induced increase in the speed of the internal pacemaker was modulated by the basal working memory capacity of each participant. These findings in healthy humans have important implications for the role of dopamine, and its contributions to timing deficits, in models of psychiatric disorders.

Self- and other-agency in people with passivity (first rank) symptoms in schizophrenia.

Individuals with passivity (first-rank) symptoms report that their actions, thoughts and sensations are influenced or controlled by an external (non-self) agent. Passivity symptoms are closely linked to schizophrenia and related disorders yet they remain poorly understood. One dominant framework posits a role for deficits in the sense of agency. An important question is whether deficits in self-agency can be differentiated from other-agency in schizophrenia and passivity symptoms. This study aimed to evaluate self- and other-agency in 51 people with schizophrenia (n=20 current, 10 past, 21 no history of passivity symptoms), and 48 healthy controls. Participants completed the projected hand illusion (PHI) with active and passive movements, as well as immediate and delayed visual feedback. Experiences of agency and loss of agency over the participant's hand and the image ('the other hand') were assessed with a self-report questionnaire. Those with passivity symptoms (current and past) reported less difference in agency between active and passive movements on items assessing agency over their own hand (but not agency over the other hand). Relative to the healthy controls, the current and never groups continued to experience the illusion with delayed visual feedback suggesting impaired timing mechanisms regardless of symptom profile. These findings are consistent with a reduced contribution of proprioceptive predictive cues to agency judgements specific to self representations in people with passivity symptoms, and a subsequent reliance on external visual cues in these judgements. Altogether, these findings emphasise the multifactorial nature of agency and the contribution of multiple impairments to passivity symptoms.

When one's sense of agency goes wrong: Absent modulation of time perception by voluntary actions and reduction of perceived length of intervals in passivity symptoms in schizophrenia.

Passivity symptoms in schizophrenia are characterised by an absence of agency for actions, thoughts and other somatic experiences. Time perception and intentional binding have both been linked to agency and schizophrenia but have not been examined in passivity symptoms. Time perception and intentional binding were assessed in people with schizophrenia (n=15 with, n=24 without passivity symptoms) and 43 healthy controls using an interval estimation procedure (200, 400 and 600ms intervals) with active, passive and observed movements. People with passivity symptoms did not display action-modulation of time perception, while those without passivity symptoms estimated intervals to be the same after active and observed movements. Additionally, both clinical samples reported intervals to be shorter with increasing interval length. We propose that impaired predictive processes may produce an overreliance on external cues and, together with shorter perceived intervals, lead to the subjective loss of agency.

The projected hand illusion: component structure in a community sample and association with demographics, cognition, and psychotic-like experiences.

The projected hand illusion (PHI) is a variant of the rubber hand illusion (RHI), and both are commonly used to study mechanisms of self-perception. A questionnaire was developed by Longo et al. (2008) to measure qualitative changes in the RHI. Such psychometric analyses have not yet been conducted on the questionnaire for the PHI. The present study is an attempt to validate minor modifications of the questionnaire of Longo et al. to assess the PHI in a community sample (n = 48) and to determine the association with selected demographic (age, sex, years of education), cognitive (Digit Span), and clinical (psychotic-like experiences) variables. Principal components analysis on the questionnaire data extracted four components: Embodiment of "Other" Hand, Disembodiment of Own Hand, Deafference, and Agency-in both synchronous and asynchronous PHI conditions. Questions assessing "Embodiment" and "Agency" loaded onto orthogonal components. Greater illusion ratings were positively associated with being female, being younger, and having higher scores on psychotic-like experiences. There was no association with cognitive performance. Overall, this study confirmed that self-perception as measured with PHI is a multicomponent construct, similar in many respects to the RHI. The main difference lies in the separation of Embodiment and Agency into separate constructs, and this likely reflects the fact that the "live" image of the PHI presents a more realistic picture of the hand and of the stroking movements of the experimenter compared with the RHI.

Revisiting the suitability of antisaccade performance as an endophenotype in schizophrenia.

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD=47, CS=46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements.

Impaired spatial working memory maintenance in schizophrenia involves both spatial coordinates and spatial reference frames.

Spatial working memory (SWM) dysfunction is a central finding in schizophrenia; however, more evidence of impaired maintenance over time is required. Consequently, the present study examined SWM maintenance over short unfilled delays, and with encoding equated. The influence of a vertical reference frame to support maintenance was also investigated. The performance of 58 patients with schizophrenia and 50 healthy controls was assessed using the Visuo-Spatial Working Memory (VSWM) Test across three unfilled delays (0, 2, and 4s). Inaccuracy of direction and distance responses was examined at each delay duration. The results showed that performance was significantly less accurate for both distance and direction responses at 2 and 4s delays in schizophrenia, but was not significantly different from controls at the 0s delay. Patients showed a particularly marked loss of accuracy between the time interval of 0-2s. Furthermore, schizophrenia participants exhibited significantly greater response variability at the vertical axis of symmetry than controls at the 2 and 4s delays, but not at the 0s delay. These data clearly show both impaired maintenance over time and difficulty using a vertical frame of reference in schizophrenia. The latter findings may reflect, in part, dysfunctional reference-related inhibition.

First-rank symptoms in schizophrenia: reexamining mechanisms of self-recognition.

Disturbances of self are a common feature of schizophrenic psychopathology, with patients reporting that their thoughts and actions are controlled by external forces, as shown in first-rank symptoms (FRS). One widely accepted explanatory model of FRS suggests a deficiency in the internal forward model system. Recent studies in the field of cognitive sciences, however, have generated new insights into how complex sensory and motor systems contribute to the sense of self-recognition, and it is becoming clear that the forward model conceptualization does not have unique access to representations about the self. We briefly evaluate the forward model explanation of FRS, reassess the distinction made between the sense of agency and body ownership, and outline recent developments in 4 domains of sensory-motor control that have supplemented our understanding of the processes underlying the sense of self-recognition. The application of these findings to FRS will open up new research directions into the processes underlying these symptoms.

Memory for speech and voice identity in schizophrenia.

Memories of conversations are composed of what was said (speech content) and information about the speaker's voice (speaker identity). In the current study, we examined whether patients with schizophrenia would show difficulties integrating speech content and speaker identity in memory, as measured in a gender-identity (male/female) recognition task. Forty-one patients and a comparison group of 20 healthy controls took part in the study. In contrast to controls, patients demonstrated greater impairments in memory for female, but not male, voices. These results are consistent with studies of speech perception that show that female voices have more complex "vocal" characteristics and require greater integration compared with male voices, and with the context memory hypothesis of schizophrenia which suggests that memory binding impairments may result in degraded or incomplete representations of memory traces as the task requirements become increasing complex.

Neuropsychological functioning in schizophrenia patients with first-rank (passivity) symptoms.

BACKGROUND: In this study, we conducted a broad investigation of neuropsychological functioning in schizophrenia patients with first-rank (passivity) symptoms (FRS) using standardized cognitive tests. We focused on 3 neuropsychological domains, partly informed by 3 broad hypotheses concerning the pathogenesis of FRS. We tested predictions that patients with FRS would show: (i) memory deficits consistent with abnormalities in medial temporal lobe functioning; (ii) reduced cerebral lateralization on tasks of motor and language functions, and (iii) deficits on tasks of executive functions as a measure of the integrity of the prefrontal cortex for supporting self-monitoring processes. SAMPLING AND METHODS: In 2 parallel studies, we administered a range of neuropsychological tests to patients with FRS (sample A = 17, sample B = 15) and without FRS (sample A = 28, sample B = 20) and to healthy controls (sample A = 109, sample B = 22). RESULTS: The results showed reduced cerebral lateralization in patients with FRS, but there were no memory deficits or executive dysfunctions relative to patients without FRS. An unexpected finding was that, on many cognitive tasks, the performance of the patients with FRS was relatively spared compared to that of the patients without FRS. These results could not be accounted for by demographic features or medication effects. CONCLUSIONS: Our results provide qualified support for the reduced lateralization hypothesis. Analyses of performance across neuropsychological domains showed that generalized deficit is not a sufficient explanation for the occurrence of FRS.

Estimating premorbid intelligence in schizophrenia patients: demographically based approach.

OBJECTIVE: The aim of the present study was to provide a useful and quick estimate of premorbid intelligence that can be used in the population of schizophrenia patients. METHOD: Regression analysis (stepwise procedure) was used to identify which of five demographic variables significantly predicted National Adult Reading Test (NART) scores in schizophrenia patients. The new regression equation was subsequently assessed in an independent patient sample. The results were compared with scores obtained for an equation developed in healthy populations. RESULTS: Age, occupation, and education contributed significantly to the equation, which accurately predicted NART scores in the patient sample. The equation developed in healthy people, however, consistently underestimated NART scores. CONCLUSIONS: Equations developed in healthy people are not accurate predictors of NART scores. By contrast, the new equation acknowledges the educational and occupational characteristics typical of individuals with schizophrenia. The equation should be used cautiously, but can be used as a rapid estimate when it is not possible to conduct a cognitive assessment using more traditional approaches.

On keeping (intrusive) thoughts to one's self: testing a cognitive model of auditory hallucinations.

BACKGROUND: Previous studies have linked intrusive cognitions (hallucinations and obsessions) with inhibitory dysregulation. Combined deficits in intentional inhibition and context memory have been proposed to explain the intrusive nature and perceived nonself origin of auditory hallucinations (Waters et al., 2006). This study tested the prediction, from this model, that individuals with obsessive-compulsive disorder (OCD), who do not mistake the origin of their intrusive thoughts, will show a deficit of intentional inhibition but intact contextual memory. METHOD: The performance of 14 individuals with OCD and 24 healthy controls was compared on two measures of intentional cognitive inhibition and on a context memory task.Results. Participants with OCD were significantly impaired on both measures of inhibition but were not significantly different from controls in any condition of the context memory task. CONCLUSIONS: The predictions were confirmed. Individuals with OCD, like schizophrenia patients with auditory hallucinations, showed impaired intentional inhibition. This impairment might be responsible for the intrusive thoughts reported in both disorders, and might also partially account for the high rates of comorbidity of OCD and schizophrenia. Finally, intact context memory abilities in OCD may contribute to an efficient memory system, and may differentiate this group from those with hallucinations.

Auditory hallucinations in schizophrenia: intrusive thoughts and forgotten memories.

INTRODUCTION: This paper presents a new cognitive model of auditory hallucinations in schizophrenia. We suggest that auditory hallucinations are auditory representations derived from the unintentional activation of memories and other irrelevant current mental associations. Our model proposes that a combination of deficits in intentional inhibition and contextual memory is critical to the experience of auditory hallucinations. The failure in intentional inhibition produces unwanted and uncontrollable mental events which are not recognised because they have lost the contextual cues that would normally facilitate recognition. METHODS: This article amalgamates recently published data and presents a reanalysis of the findings on 43 patients with a diagnosis of schizophrenia (Badcock, Waters, Maybery, & Michie, 2005; Waters, Badcock, Maybery, & Michie, 2003a; Waters, Maybery, Badcock, & Michie, 2004a). Relative risk was also estimated to determine whether the combination of deficits increases the risk of having auditory hallucinations. RESULTS: Almost 90% of patients currently experiencing auditory hallucinations showed the predicted combination of deficits on both inhibition and context memory, compared to only a third of patients without hallucinations. In addition, the results showed that those patients with the specified cognitive deficits were at an especially increased risk of having auditory hallucinations relative to patients without the deficits. CONCLUSIONS: The results of our investigations strongly support the role of intentional inhibition and context memory in auditory hallucinations. Critical consideration of the findings also suggests that additional cognitive processes might be important for the expression of this symptom.

Selective attention for negative information and depression in schizophrenia.

OBJECTIVES: Depression is a frequent feature of schizophrenia but the cognitive processes involved in its development and maintenance are unclear. Recent studies have shown that clinical depression is associated with faulty inhibitory mechanisms of selective attention for negative information. The current study examined whether patients with schizophrenia also have an attentional bias towards negative stimuli. The inhibitory processes of interference control and task-shifting abilities were also examined to assess whether patients would show a selective impairment. METHOD: Forty-three patients with schizophrenia and 24 healthy controls completed the Affective Shifting Task. RESULTS: As a group, schizophrenia patients did not show an attentional bias for negative material. However, those patients with high levels of depression demonstrated faster latencies when negative words were the targets, and higher depression scores were found to be associated with an increasing number of false alarms for negative words when they were not the targets. The results also showed that patients had impaired interference control but intact task-shifting abilities. CONCLUSIONS: Faulty inhibitory mechanisms of selective attention for negative information are not a general feature of schizophrenia but appear to be selective to those with a depressed mood. The results highlight the need for further studies examining the exact nature of the affective dysfunction in schizophrenia and the cognitive processes supporting negative emotions.

Dimensions of intelligence in schizophrenia: evidence from patients with preserved, deteriorated and compromised intellect.

There is a growing literature describing a subgroup of "high-functioning" people with schizophrenia who show preserved intellectual ability (IQ). A detailed characterisation of the cognitive abilities of this group may be important in targeting appropriate treatment, management and services for patients with schizophrenia. It is a widely held belief that variation in cognitive processing speed is the basis of individual differences in intelligence. The main objective of this study was to identify subgroups of schizophrenia patients with preserved (N=45), deteriorated (N=47) and compromised (N=17) intellect in order to study whether these subgroups differ in specific cognitive abilities (e.g. executive functions) or in general cognitive processing speed, as measured with an inspection time (IT) task. The patients who displayed an average estimated premorbid IQ, with no evidence of IQ decline (premorbid-current IQ difference <10 points), were found to show better performance on measures of executive function (continuous performance task, verbal fluency) compared with patients in the deteriorated and compromised subgroups. Nevertheless, this represented significantly impaired performance relative to healthy controls. In contrast, the average inspection times of patients with preserved IQ were as slow as those obtained in the deteriorated or compromised groups, indicating that high functioning patients are impaired in terms of cognitive processing speed. Furthermore, the average IT for all schizophrenia groups was significantly slower than that of healthy controls. These findings suggest that high functioning patients with schizophrenia exhibit enduring cognitive difficulties that may impact on their ability to benefit from rehabilitation interventions.

Auditory hallucinations: failure to inhibit irrelevant memories.

INTRODUCTION: The frequency of auditory hallucinations (AH) is associated with efficiency in inhibiting irrelevant memories, suggesting that the presence of AH may be related to the intrusion of strongly activated representations in memory. Therefore, we hypothesised that the inability to suppress irrelevant memories would be found only in patients currently experiencing AH. METHOD: Performance on a repeated, continuous recognition task was examined in 23 schizophrenia patients with AH present, 20 schizophrenia patients with AH absent, and 24 healthy controls. RESULTS: Patients with current AH made significantly more inappropriate responses (false alarms) to distractors seen on previous runs of the task than nonhallucinating patients. The ability to detect targets (hits) was significantly better in healthy controls than schizophrenia patients, however, there was no significant difference between the two patient subgroups. CONCLUSIONS: The findings confirm that the presence of AH involves a failure to suppress memories that are not relevant to ongoing reality. We propose that a combination of deficits in inhibition and (episodic) memory provides a useful model of AH, which can accommodate many of the characteristic features of the symptom and fits well with the neuroanatomical circuitry that is believed to underlie the occurrence of AH.

Context memory and binding in schizophrenia.

The current study aimed to provide evidence for the context-memory hypothesis, which proposes that schizophrenia is linked to a deficit in retrieving contextual information and in binding the different components of a memory together. A new task was developed in which memory for the content of events could be assessed in conjunction with memory for both source and temporal information. Forty-three patients with schizophrenia and 24 normal controls took part in the study. Patients were found to be less accurate in identifying the source and temporal context of events. Furthermore, whereas controls tended to identify correctly both source and temporal context of events, patients tended to have a more fractionated recollection of those events. The study provides support for the context-memory hypothesis by demonstrating that patients with schizophrenia show a fundamental deficit in binding contextual cues together to form a coherent representation of an event in memory.

Inhibition in schizophrenia: association with auditory hallucinations.

The study investigated whether auditory hallucinations (AH) in schizophrenia are linked to a deficit in inhibition. Two tasks assessing the intentional suppression of cognitive events-the Hayling Sentence Completion Test (HSCT) [Neuropsychologia 34 (1996) 263] and the Inhibition of Currently Irrelevant Memories Task (ICIM) [Nature Neuroscience 2 (1999) 677]-were administered to 42 patients with schizophrenia and 24 normal controls. Presence and severity of symptoms in the patient group were examined using the Positive and Negative Syndrome Scale (PANSS). Patients performed significantly worse on the measures of inhibition compared to controls. More importantly, among patients, significant positive correlations were obtained between an index of AH severity (defined as an increase in frequency of AH on PANSS) and the number of type A errors on the HSCT and errors in the last three runs of the ICIM. An increase in AH severity was, therefore, associated with increasingly impaired control of intentional inhibition. Furthermore, no significant correlations were found between these indices of inhibition and either negative, general or positive symptoms (excluding AH scores).