Degraded Stimulus Continuous Performance Test Research Articles

Neurocognitive profile of adolescents with early-onset schizophrenia and their unaffected siblings

Background We investigated the neurocognitive profiles of Early-Onset Schizophrenia (EOS; onset before age 18) and paired unaffected siblings and the little-studied effect of age-of-onset and duration of illness on cognitive performance. Methods 31 EOS probands, and 31 of their siblings, had four cognitive domains assessed: (a) Memory: California Verbal Learning Test, and the Wechsler Memory Scale-Revised; (b) Working memory: Digit Span; (c) Attention: Degraded-Stimulus Continuous Performance Test, Span of Apprehension (SPAN), and Trail Making Test (TMT) part A; (d) Executive function: Wisconsin card sorting task, and TMT part B. Diagnosis was confirmed using the structured clinical interview for DSM-IV. Results While EOS showed a generalised neurocognitive deficit (0.25–0.50 effect size) compared with siblings, across all cognitive domains, significantly greater patient deficits were observed with, working memory, attention, and executive function and minimal differences for digit span forward, block design and false alarms on the SPAN-12 confirmed by repeated measures MANOVA. Patients with earlier onset (12–15) showed greater deficits on false alarm and digits backward scores. Siblings showed individual cognitive task profiles similar to patients, confirming familial effects. EOS showed much more variable scores than siblings with more individual tasks showing 2 SD deficits than siblings. Long duration patients had greater z-score variability across tasks. Conclusions Duration of illness was a more important characteristic in patients with onset 16 and over than in younger onset patients with comparable durations. Both the similarity of sibling pair profiles and greater patient variability across task provide further support for neurobiological heterogeneity in schizophrenia.

Attention/vigilance in schizophrenia: Performance results from a large multi-site study of the Consortium on the Genetics of Schizophrenia (COGS)

Attention/vigilance impairments are present in individuals with schizophrenia across psychotic and remitted states and in their first-degree relatives. An important question is whether deficits in attention/vigilance can be consistently and reliably measured across sites varying in many participant demographic, clinical, and functional characteristics, as needed for large-scale genetic studies of endophenotypes.We examined Continuous Performance Test (CPT) data from phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the largest-scale assessment of cognitive and psychophysiological endophenotypes relevant to schizophrenia. The CPT data from 2251 participants from five sites were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS-CPT) and a memory-load vigilance task (CPT-Identical Pairs or CPT-IP) were utilized.Schizophrenia patients performed more poorly than healthy comparison subjects (HCS) across sites, despite significant site differences in participant age, sex, education, and racial distribution. Patient–HCS differences in signal/noise discrimination (d′) in the DS-CPT varied significantly across sites, but averaged a medium effect size. CPT-IP performance showed large patient–HCS differences across sites. Poor CPT performance was independent of or weakly correlated with symptom severity, but was significantly associated with lower educational achievement and functional capacity. Current smoking was associated with poorer CPT-IP d′. Patients taking both atypical and typical antipsychotic medication performed more poorly than those on no or atypical antipsychotic medications, likely reflecting their greater severity of illness.We conclude that CPT deficits in schizophrenia can be reliably detected across sites, are relatively independent of current symptom severity, and are related to functional capacity.

Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia.

The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods. Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results.

NR4A2: Effects of an “Orphan” Receptor on Sustained Attention in a Schizophrenic Population

NR4A2 (nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence of NR4A2 gene in the performance of schizophrenia (SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs in NR4A2 gene: rs1150143 (C/G), rs1150144 (A/G), rs834830 (A/G), rs1466408 (T/A), and rs707132 (A/G). We also analyzed the influence of its haplotypes (frequency>5%). To examine sustained attention, all the individuals completed the Degraded Stimulus Continuous Performance Test. We evaluated "hits," "reaction time," "sensibility a," and "false alarms." In the schizophrenic group, recessive genotypes of rs1150143, rs1150144, rs834830, and rs707132 were associated with a worse performance. SZ subjects who carried GGGTG haplotype showed less hits (P<.004), lower sensibility a scores (P<.009), and a higher reaction time (P=.013). We observed a sex effect of the gene: genotype and haplotype associations were only present in the male group. We conclude that NR4A2 gene is involved in attentional deficits of SZ patients, modifying hits, sensibility a, and reaction time.

Behavior regulation and mood predict social functioning among healthy young adults

Impulsive behavior is thought to lead to both positive and negative psychosocial outcomes. However, little is known about the potential consequences of subclinical expressions of behavior dysregulation on everyday functioning. To examine this relationship, global social functioning was measured in 89 healthy, young adults who also completed the Degraded Stimulus Continuous Performance Test, Color–Word Interference Test, Barratt Impulsiveness Scale, 11th Edition, and Behavior Rating Inventory of Executive Functioning–Adult. Better self-reported executive functioning and mood were significant independent predictors of higher social functioning, even in a sample of healthy adults. The results of this study may serve as a foundation for comparison with clinical populations who demonstrate greater behavior dysregulation and mood instability.

P03-218 Neurocognitive vulnerability indicators in psychosis

Background:Cognitive impairments are considered a component of the extended clinical syndrome of schizophrenia. the aim of the current project was to investigate putative cognitive deficits in individuals with Early Onset Schizophrenia (EOS; defined herein as onset before the age of 18) and their relatives.Methods:53 EOS probands and 117 unaffected first-degree-relatives were examined on memory (Wechsler Memory Scale-Revised), verbal learning and recognition (California Verbal Learning Test), and attention (SPAN of apprehension test and degraded-stimulus continuous performance test (DS-CPT)). the Structured Clinical Interview for DSM-IV yielded four diagnostic groups: EOS probands; relatives with Mood Disorders; other Axis I diagnoses; and no diagnosis (healthy). Analysis of co-variance was performed with diagnosis as fixed factor and age as covariate.Results:EOS probands under performed on General Memory, Verbal Memory and Delayed Recall indices (WMS-R) compared to their relatives. both EOS and relatives with a mood disorder performed less well on Visual memory and Attention/Concentration indices [p&lt; 0.001]. Relatives without Axis I diagnosis differentiated from EOS on all indices [p&lt; 0.01]. Verbal learning and recognition impairments segregated in EOS and differentiated patients from their relatives. EOS probands and relatives with an Axis I diagnoses showed rapid visual information processing impairments (SPAN) compared to healthy relatives, while sustained attention (DS-CPT) remained relatively preserved in EOS and relatives.Conclusions:Genetic predisposition to schizophrenia may be mediated by visual information processing impairments, which differentiates healthy relatives from relatives with an Axis I diagnosis. Sustained attention seems to be a selective strength in EOS and relatives.

Neuropsychological Near Normality and Brain Structure Abnormality in Schizophrenia

Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness. Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates. Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects. Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.

Effects of cigarette smoking on prepulse inhibition, its attentional modulation, and vigilance performance

Startle eyeblink modification was measured during a degraded stimulus continuous performance test following both smoking and overnight abstinence among student smokers to measure the effects of smoking on both early and late attentional processes. A group of nonsmokers was tested twice without nicotine manipulation. A startling noise was presented either 240 or 1200 ms following target and nontarget stimuli presented during the task. Startle inhibition at 240 ms was greater following targets than nontargets following smoking and during both nonsmoker tests, but this attentional modulation was absent following abstinence. At the 1200-ms probe position, target and nontarget stimuli produced nondifferential inhibition during both tests for both groups. Abstinence among smokers produced reliably lower vigilance performance compared to ad lib smoking. The results indicate that smoking abstinence affects the early stages of stimulus processing.

Inferior frontal white matter microstructure and patterns of psychopathology in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder

Background:Inferior frontal white matter circuits are likely to be relevant to dysfunctional affect regulation, aggression, dissociative symptoms, neuropsychological functioning and psychopathology in women with borderline personality disorder (BPD) and comorbid attention-deficit hyperactivity disorder (ADHD). Methods:20 women with BPD and comorbid ADHD and 20 healthy women were investigated, and groups were matched for age, education and premorbid intelligence. Mean diffusivity and fractional anisotropy were measured bilaterally in the inferior frontal white matter by diffusion tensor imaging (DTI). Conflict resolution was assessed by the Attention Network Test, sustained vigilance by the Degraded-Stimulus Continuous Performance Test. Results:Among women with BPD and comorbid ADHD, increased mean diffusivity in inferior frontal white matter was associated with higher levels of dysfunctional affect regulation, anger–hostility, dissociative symptoms, and general psychopathology (p<.05, uncorrected). Poor conflict resolution during the attention task was positively associated with anger–hostility, psychopathology, dissociation and the number of ADHD-symptoms, but not related to DTI variables. Both groups did not differ significantly with respect to DTI variables or neuropsychological performance. In the BPD group, a lifetime history of major depression or a current eating disorder were associated with impaired inferior frontal white matter integrity, while a history of sexual abuse or a current posttraumatic stress disorder were not. Conclusions:Inferior frontal white matter microstructural abnormalities may be linked to key aspects of psychopathology in women with BPD and comorbid ADHD and add to alterations in orbitofrontal and limbic areas. The relationship between neuropsychological functioning and white matter structure remains unclear.

Effects of perceptual processing demands on startle eyeblink modification

Startle eyeblink modification was measured during a continuous performance test (CPT) with either clearly focused stimuli or visually degraded stimuli to measure the effects of early perceptual processing demands on startle modification. A startling noise was presented either 120, 240, or 1200 ms following target and nontarget CPT stimuli. In the degraded stimulus CPT, startle inhibition at 240 ms was greater following targets than nontargets and was as great during targets at 240 ms as at 120 ms, whereas in the clearly focused CPT, inhibition declined significantly from 120 to 240 ms. The results indicate that maximum prepulse inhibition is extended in time when the task involves discrimination of degraded visual stimuli and when early perceptual processing demands are high. At 1200 ms, targets and nontargets produced nondifferential inhibition during both CPTs, suggesting that modality-specific attention occurred equally for the two tasks.

Is unawareness of psychotic disorder a neurocognitive or psychological defensiveness problem?

We examined whether deficits in attention and perceptual encoding as well as psychological defensiveness were associated with impaired awareness of disorder in schizophrenia. The Scale for Unawareness of Mental Disorder (SUMD) was administered to 52 outpatients with a recent onset of schizophrenia approximately 1–2 months following hospital discharge. Two versions of the Continuous Performance Test (CPT) were used to measure attentional impairment—the Degraded Stimulus CPT (DS-CPT) and a memory-load version (3-7 CPT). Three scales from the Minnesota Multiphasic Personality Inventory were used as indicators of psychological defensiveness: Scales L (Lie), K (Correction), and R (Repression). The Classification and Regression Tree (CART) program, a nonparametric statistical method, was used to identify relationships among multiple predictor variables and to provide optimal splitting scores for each predictor variable. Different combinations of poor target discrimination ( d′) on the 3-7 CPT and a cautious response style on the DS-CPT were associated with the three levels of overall unawareness of having a mental disorder. For nonpsychotic patients, better target discrimination ( d′) on the 3-7 CPT tended to be associated with better awareness of having a mental disorder. In contrast, unawareness among the patients who were psychotic at the time of the SUMD administration was not discriminated by attentional measures, but was associated with a combination of two measures of psychological defensiveness from the MMPI reflecting guardedness, psychological suppression, attempting to present oneself in a socially desirable light, and social acquiescence. Generally similar associations were found for two other dimensions of poor insight: unawareness of the beneficial effects of antipsychotic medication, and inability to attribute unusual thoughts and hallucinatory experiences to a mental disorder.

Psychophysiological index during auditory selective attention correlates with visual continuous performance test sensitivity in normal adults

The continuous performance test (CPT) provides a reliable index of cognitive function, but it is still unclear what aspects of processing this test measures. This study aimed to investigate the contribution of different aspects of cognitive function to the performance on degraded stimulus CPT (DSCPT), which requires a higher level of mental effort than the conventional CPT. Event-related potential (ERP) components, MMN, N2b, and early and late Nds were measured at 16 electrode sites in 19 right-handed normal volunteers using an auditory selective attention task. The association between CPT sensitivity ratings (sensitivity A′) and amplitudes of each component was examined for each electrode site. The CPT sensitivity A′ showed a significant positive correlation with the N2b amplitude in the fronto-central and temporal regions, predominantly in the right hemisphere and specifically to the right ear of stimulation. This finding suggests that the controlled deviance detection process was related to DSCPT performance.

The vigilance paradigm in schizophrenia research - studies on the Continuous Performance Test (CPT)

Deficits in vigilance/sustained attention of schizophrenic subjects have been a main topic of neuropsychological schizophrenia research for many years. The degraded stimulus Continuous Performance Test (ds-CPT) is the standard paradigm for measuring vigilance. Measurement of vigilance requires the observation of the course of perceptual sensitivity over time. The present review shows that from a theoretical point of view it is possible to show vigilance deficits (as a decrease of sensitivity) with the ds-CPT if certain conditions are given. However, only in a few schizophrenia studies the course of sensitivity over time was evaluated, while in most studies merely the level of sensitivity was analysed. Results presented in this review suggest that level and course of sensitivity are largely independent variables. Vigilance can be operationalised adequately only when considering the course of sensitivity over time. Therefore there still is a considerable need for research on the meaning of vigilance deficits for manifestation, course and treatment of schizophrenia.

Persistent attentional dysfunction in remitted bipolar disorder.

Although previous research has shown that attentional dysfunction is common during acute mood episodes in individuals with bipolar disorder (BPD), few studies have examined whether attentional deficits are evident during periods of symptom stability. The goal of this study was to determine whether clinically stable individuals with BPD would have attentional disturbances relative to healthy subjects. Fourteen patients with BPD and 12 healthy comparison subjects participated in the study, and were administered the Degraded Stimulus Continuous Performance Test (DSCPT), Digit Span Distractibility Test (DSDT) and Grooved Pegboard Test (GPT). Psychiatric symptoms were assessed with the Young Mania Rating Scale and the Scale for the Assessment of Positive Symptoms. Medication side effects were measured with the Simpson Rating Scale. The patient group responded significantly more slowly than the control group on the DSCPT (z = -2.52, p = 0.01) and the GPT (z = -3.37, p = 0.001). There was a trend towards the BPD patients demonstrating impaired perceptual sensitivity on the DSCPT (z = 1.68, p = 0.09). The two groups did not differ on the DSDT (z = -1.06, p = 0.3). Poor performance on the GPT and DSCPT target reaction time were not associated with symptom ratings or medications. The findings suggest that impairments in fine motor skills and reaction time may be present in clinically stable patients with BPD, even after accounting for psychiatric symptoms and medication effects. Performance decrements on attentional tasks may be in part reflective of motor impairments in patients with BPD.

Sustained and selective attention as measures of genetic liability to schizophrenia

We tested for a relationship between attention and genetic liability to schizophrenia. Samples of probands with DSM-IV schizophrenia ( n=20), their well first-degree relatives ( n=40) and healthy controls ( n=82) were tested using measures of sustained attention (degraded-stimulus continuous performance test: DS-CPT) and selective attention (spatial negative priming task). Assuming a liability-threshold model, we predicted that probands would display greater attentional decrements than controls and that the relatives would show intermediate levels of decrement. We did not observe the predicted pattern of effect using either measure, although the probands showed a trend towards less negative priming. However, our results may have been affected by self-selection bias in probands and relatives and clinical heterogeneity among probands, which could have reduced our power to detect effects.

Attentional characteristics of schizophrenia patients differing in learning proficiency on the Wisconsin Card Sorting Test.

The Wisconsin Card Sorting Test (WCST), a test of concept formation, was given to 49 schizophrenia inpatients in three blocks of 64 cards each with the second block comprising special instructions and trial-by-trial feedback. With the help of a psychometric algorithm based on linear regression analysis, the patients were classified according to their response to these specific interventions. Results yielded 15 high scorers, 23 learners, and 11 nonlearners. This a priori classification was confirmed by cluster analysis. Next, these groups were further analyzed with the Degraded Stimulus Continuous Performance Test (DS-CPT), a test of target discrimination, and the Test of Attentional Style (TAS), which assesses habitual, subjectively experienced attentional problems. A significant difference between high scorers and nonlearners was found for discriminative sensitivity (d'), with the learners achieving intermediate scores. Results for only the DS-CPT response criterion (beta) and a TAS subscale (Distractibility) tended to be significant. Discriminant analysis also revealed that d' is the most powerful variable for discriminating among the subgroups. The article also addresses baseline versus dynamic assessment, specific rehabilitation needs in subgroups of schizophrenia patients different in learner status, and the neurocognitive characteristics of the subgroups.

Psychophysiological correlates of social skills deficits in persons with schizophrenia

Social skill deficits in schizophrenia profoundly affect patients’ life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.

Sustained attention in patients with obsessive–compulsive disorder: a controlled study

Studies on attentional processes in obsessive–compulsive disorder (OCD) have been inconsistent. The present study focused on the question of sustained attention in OCD, using the ‘Degraded Stimulus Continuous Performance Test’ (DS-CPT) sensitivity index over time. This study included 20 OCD patients and 25 control subjects, comparable in sex, age and educational level. All subjects had a neuropsychiatric structured diagnostic interview, as well as a psychometric battery. The DS-CPT evaluated sustained attention. The sensitivity decrement during DS-CPT was significant in both controls and OCD subjects. Contrary to our expectations, OCD patients did not show a greater decrease in sensitivity over time, compared to controls: thus, OCD patients presented a no more important attention decrease than controls. Controls and OCD subjects became more conservative in their response criteria throughout the DS-CPT test. Comparing OCD with and without pharmacological treatment did not reveal any difference in CPT outcome. Moreover, we observed, in OCD, a positive significant correlation between the Y-BOCS compulsion score and the CPT sensitivity index. A significant negative correlation of the Y-BOCS compulsive score with the CPT false alarm score was also found. In conclusion, OCD patients did not present any disturbance in sustained attention during a task requiring an increased processing load.

Perception of emotion and neurocognitive functioning in schizophrenia: what's the link?

In schizophrenia, relatively little is known about the association between deficits in emotion perception and basic neurocognitive functioning. The present study examined perception of emotion and a discrete set of neurocognitive functions in 28 treatment-resistant schizophrenic patients. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception test (brief interpersonal vignettes presented on videotape). Measures of neurocognitive functioning were selected based on hypothesized relationships to perception of emotion. These measures included: (a) Span of Apprehension task, a measure of early visual processing, visual scanning, and iconic read-out; (b) Degraded-Stimulus Continuous Performance Test, a measure of visual vigilance; and (c) Digit Span Distractibility Test, a measure of immediate or working memory. Among these measures, performance on the Span of Apprehension strongly correlated with performance on all three emotion perception tasks. The associations between perception of emotion and the other two measures were in the same direction, but were significantly smaller than those of the Span of Apprehension. These findings implicate the importance of early perceptual processing (i.e. visual scanning) in the ability of schizophrenic individuals to perceive emotion.

Symptom correlates of attentional improvement following hospitalization for a first episode of affective psychosis

Background: This study examined patients with a first-episode of affective psychosis during acute and compensated states in order to determine whether changes in attentional functioning over time were accompanied by changes in the severity of psychotic or affective symptoms. Methods: Attentional performance was measured in patients ( n = 27) using the degraded-stimulus Continuous Performance Test (CPT) and symptoms were assessed at the time of index hospitalization, and 2 months after discharge. A comparison group of normal volunteers ( n = 31) also performed the CPT two months apart. Results: Patients performed significantly worse than controls at the initial testing but not at follow-up. The improvement in attentional performance significantly correlated with decreased severity of manic symptoms. Conclusions: Results suggest attentional dysfunction is a state-dependent characteristic of mania, and may provide an additional measure of clinical improvement following treatment.