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Poster #155 EVALUATION OF A RULE SWITCHING TEST DESIGNED TO ASSESS EXECUTIVE CONTROL
S336
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
Department of the UMCG between 1997 and 2009 were included in the analysis, yielding a representative cohort for the province of Groningen (550,000 inh.). Assessment included: DSM-IV-diagnosis (SCAN-interview), co-morbidity, two successive PANSS-interviews, family history, live-events, prescribed antipsychotic medication, substance abuse and cultural background. A comprehensive neuropsychological test battery was administered: Intelligence (WAIS, short version), Continuous Performance Test (CPT) Hitrate and D-prime, Fingertapping, California Verbal Learning Test (CVLT), Stroop and Trailmaking. Normative measures were created by comparing the patients’ performance with performance of matched healthy controls. Next, neuropsychological profiles were formed in 464 patients (Caucasian, diagnosis in psychotic spectrum), using hierarchical and subsequent K-Means–cluster analysis on the WAIS, CPT-D’prime, Fingertapping, CVLT-Recall, Stroop and Trailmaking. Results: On average, patients performed within normal range on the CPT and Fingertapping tasks. They performed 1 sd worse than controls on recall measures in the CVLT, and were 1.5 sd slower than controls on time measures in the Stroop and Trailmaking tasks. Interference measures of Stroop and Trailmaking tasks were normal in patients. Preliminary findings in 463 patients by K-Means–cluster analysis suggest three neuropsychological profiles: i) normal or fast achieving (19%), ii) poor on “motor-speed”/“verbal learning and memory”, iii) poor on “selective and divided attention”. Discussion: Overall, these results suggest that FE Patients perform slightly slower than normal controls, however, a substantial proportion of FE patients (19%), is performing neuropsychologically within normal limits. The loss of speed in task performance appears to be independent of the complexity of the tests. Three neuropsychological profiles may yield large intergroup differences. In a follow-up study, these neuropsychological profiles will be linked with clinical measures, sociodemographic factors and measures of functional outcome.
Poster #154 THE CENTRAL ROLE OF ATTENTION AND INFORMATION PROCESSING DEFICITS IN THE PROFILE OF COGNITIVE DYSFUNCTION IN SCHIZOPHRENIA Keith Wesnes 1,2 , Chris Edgar 1 , Lawrence Brownstein 3 , Howard Hassman 3 , Eden Evins 4 1 Bracket, Goring, United Kingdom; 2 Swinburne University, Melbourne, Australia; 3 CRI Worldwide Mount, Laurel, NJ, USA; 4 Harvard Medical School, Boston, MA, USA Background: The current interest in cognition in schizophrenia has been in part fuelled by the MATRICS initiative, and numerous research programs are now focussing upon targeted domains including speed of processing, attention/vigilance, working memory, verbal memory and visual memory. Deficits to attention have long been believed to be a central part of the cognitive impairment profile in schizophrenia (eg McGhie A, Chapman J, Lawson JS. Disturbances in Selective Attention in Schizophrenia, Proc R Soc Med 1964; 57: 419–422). This paper will further seek to understand the role played by attention and information processing in the overall profile of cognitive impairments in schizophrenia, using data from several cohorts of patients. Methods: The CDR System is a computerised cognitive test system which has been used in worldwide clinical trials for over 25 years. The System assesses various aspects of attention and information processing, executive control, spatial working memory, articulatory working memory, as well as visual and verbal episodic memory. CDR System data from several cohorts of schizophrenic patients and controls will be analyzed using ANOVA, ANCOVA, correlation and regression techniques. Results: In each cohort, aspects of information processing, most notably speed on tests of focussed and sustained attention showed the largest effect sizes of impairments compared to healthy age and gender matched controls. The Cohen’s d effect sizes of the impairments ranged from 1.4 for first time diagnosed previously unmedicated patients up to over 4 in the other schizophrenic populations who were on stable medication. A range of deficits to other aspects of cognition were seen generally in excess of the definition of large effects sizes (0.8). The extent to which the attentional impairments were responsible for the other deficits was examined using regression and covariance techniques. Speed on attention tasks are correlated with working and episodic memory performance in the various
patient populations (r=0.4 or above), but not in controls (r<0.1). Deficits to spatial working memory and episodic verbal memory disappear when speed on attention tasks as well as speed of processing in memory tasks are fitted as covariates, while articulatory working memory and visual episodic memory deficits remain, but with reduced magnitudes. The central role of speed of processing will be further examined by establishing relationships with other factors such disease severity, type of medication and duration of illness. Discussion: Overall the patterns of data from these analyses suggest a central role for attention and information processing deficits in the cognitive pathology of schizophrenia. Such findings identify these attention and information processing deficits as primary targets for drug therapies aimed at improving cognitive function in schizophrenia.
Poster #155 EVALUATION OF A RULE SWITCHING TEST DESIGNED TO ASSESS EXECUTIVE CONTROL Keith Wesnes 1,2 , Chris Edgar 1 , Richard Wojciak 3 , Alicia Craig-Rodriguez 3 , Maria Pinho 3 , David Kreftez 3 , Daniel Gruener 3 , Lawrence Brownstein 3 , Howard Hassman 3 1 Bracket, Goring, United Kingdom; 2 Swinburne University, Melbourne, Australia; 3 CRI Worldwide, Philadelphia, PA, USA Background: Executive function is a set of cognitive abilities that control and regulate other aspects of function to facilitate goal-directed behaviour. One experimental paradigm for assessing aspects of executive control is requiring subjects to switch between two tasks. We evaluated a test in which such switching has previously been shown to involve activation of the medial and dorsolateral areas of the frontal cortex (DiGirolamo GJ et al. General and task-specific frontal lobe recruitment in older adults during executive processes: A fMRI investigation of task-switching. NeuroReport 2010, 12: 2065-2071). Methods: In this rule switching test (RST), strings of identical digits of varying length are presented on a computer screen (eg 888, 111111, 3333). In one condition, the subject has to determine whether the number of digits in each string is greater or smaller than 5, and in another condition whether the value of the digits is greater or smaller than 5. There are never 5 digits in the string and the digit 5 is not used. Each condition is associated with a particular colour which is presented before each string. The subject initially performs each condition separately in a block of 36 trials. Then in the “switching” phase, the subject is required to apply the rule according to the colour presented prior to each successive string; the colors being presented in an unpredictable sequence, forcing the subject to decide which rule to apply trial by trial. In the present study, 41 healthy volunteers aged 21 to 55 years performed the RST on three study days alongside Parts A and B of the trail making test (TMT). Part A of the TMT involves a single rule, while Part B involves rule switching. Analysis of variance was used to compare the performance between the various phases of the RST and correlations were run to establish test-retest reliability and examine relationships between the two tests and performance with the age of the volunteers. Further studies using the same methodology are underway using schizophrenic and bipolar patients. Results: In the RST, the subjects took significantly longer to respond in the switching phase than when performing the task using either one of the rules (p<0.001), this performance change reflecting the demands of rule switching and providing an assessment of executive control. The test-retest reliability of the speed scores in the switching and non-switching conditions of the RST was good (r=0.58 to 0.89), as was that for Parts A and B of the TMT (r=0.60 to 0.87). There were also statistically significant correlations between the RST switching condition and Part B of the TMT (r=0.37, p<0.02), as well as between the extra response time in the switching condition of the RST and the longer completion time of the TMT Part B (r=0.32, p<0.05). Further, the extra response time in the switching condition of the RST correlated with the age of the volunteers (r=0.5, p<0.001), indicating that the test is sensitive to age-related declines. Discussion: The RST appears to be suitable for repeatedly assessing executive control over time in clinical trials with volunteers. Early readouts of the data from follow up trials with schizophrenic and bipolar patients will be presented.
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
Department of the UMCG between 1997 and 2009 were included in the analysis, yielding a representative cohort for the province of Groningen (550,000 inh.). Assessment included: DSM-IV-diagnosis (SCAN-interview), co-morbidity, two successive PANSS-interviews, family history, live-events, prescribed antipsychotic medication, substance abuse and cultural background. A comprehensive neuropsychological test battery was administered: Intelligence (WAIS, short version), Continuous Performance Test (CPT) Hitrate and D-prime, Fingertapping, California Verbal Learning Test (CVLT), Stroop and Trailmaking. Normative measures were created by comparing the patients’ performance with performance of matched healthy controls. Next, neuropsychological profiles were formed in 464 patients (Caucasian, diagnosis in psychotic spectrum), using hierarchical and subsequent K-Means–cluster analysis on the WAIS, CPT-D’prime, Fingertapping, CVLT-Recall, Stroop and Trailmaking. Results: On average, patients performed within normal range on the CPT and Fingertapping tasks. They performed 1 sd worse than controls on recall measures in the CVLT, and were 1.5 sd slower than controls on time measures in the Stroop and Trailmaking tasks. Interference measures of Stroop and Trailmaking tasks were normal in patients. Preliminary findings in 463 patients by K-Means–cluster analysis suggest three neuropsychological profiles: i) normal or fast achieving (19%), ii) poor on “motor-speed”/“verbal learning and memory”, iii) poor on “selective and divided attention”. Discussion: Overall, these results suggest that FE Patients perform slightly slower than normal controls, however, a substantial proportion of FE patients (19%), is performing neuropsychologically within normal limits. The loss of speed in task performance appears to be independent of the complexity of the tests. Three neuropsychological profiles may yield large intergroup differences. In a follow-up study, these neuropsychological profiles will be linked with clinical measures, sociodemographic factors and measures of functional outcome.
Poster #154 THE CENTRAL ROLE OF ATTENTION AND INFORMATION PROCESSING DEFICITS IN THE PROFILE OF COGNITIVE DYSFUNCTION IN SCHIZOPHRENIA Keith Wesnes 1,2 , Chris Edgar 1 , Lawrence Brownstein 3 , Howard Hassman 3 , Eden Evins 4 1 Bracket, Goring, United Kingdom; 2 Swinburne University, Melbourne, Australia; 3 CRI Worldwide Mount, Laurel, NJ, USA; 4 Harvard Medical School, Boston, MA, USA Background: The current interest in cognition in schizophrenia has been in part fuelled by the MATRICS initiative, and numerous research programs are now focussing upon targeted domains including speed of processing, attention/vigilance, working memory, verbal memory and visual memory. Deficits to attention have long been believed to be a central part of the cognitive impairment profile in schizophrenia (eg McGhie A, Chapman J, Lawson JS. Disturbances in Selective Attention in Schizophrenia, Proc R Soc Med 1964; 57: 419–422). This paper will further seek to understand the role played by attention and information processing in the overall profile of cognitive impairments in schizophrenia, using data from several cohorts of patients. Methods: The CDR System is a computerised cognitive test system which has been used in worldwide clinical trials for over 25 years. The System assesses various aspects of attention and information processing, executive control, spatial working memory, articulatory working memory, as well as visual and verbal episodic memory. CDR System data from several cohorts of schizophrenic patients and controls will be analyzed using ANOVA, ANCOVA, correlation and regression techniques. Results: In each cohort, aspects of information processing, most notably speed on tests of focussed and sustained attention showed the largest effect sizes of impairments compared to healthy age and gender matched controls. The Cohen’s d effect sizes of the impairments ranged from 1.4 for first time diagnosed previously unmedicated patients up to over 4 in the other schizophrenic populations who were on stable medication. A range of deficits to other aspects of cognition were seen generally in excess of the definition of large effects sizes (0.8). The extent to which the attentional impairments were responsible for the other deficits was examined using regression and covariance techniques. Speed on attention tasks are correlated with working and episodic memory performance in the various
patient populations (r=0.4 or above), but not in controls (r<0.1). Deficits to spatial working memory and episodic verbal memory disappear when speed on attention tasks as well as speed of processing in memory tasks are fitted as covariates, while articulatory working memory and visual episodic memory deficits remain, but with reduced magnitudes. The central role of speed of processing will be further examined by establishing relationships with other factors such disease severity, type of medication and duration of illness. Discussion: Overall the patterns of data from these analyses suggest a central role for attention and information processing deficits in the cognitive pathology of schizophrenia. Such findings identify these attention and information processing deficits as primary targets for drug therapies aimed at improving cognitive function in schizophrenia.
Poster #155 EVALUATION OF A RULE SWITCHING TEST DESIGNED TO ASSESS EXECUTIVE CONTROL Keith Wesnes 1,2 , Chris Edgar 1 , Richard Wojciak 3 , Alicia Craig-Rodriguez 3 , Maria Pinho 3 , David Kreftez 3 , Daniel Gruener 3 , Lawrence Brownstein 3 , Howard Hassman 3 1 Bracket, Goring, United Kingdom; 2 Swinburne University, Melbourne, Australia; 3 CRI Worldwide, Philadelphia, PA, USA Background: Executive function is a set of cognitive abilities that control and regulate other aspects of function to facilitate goal-directed behaviour. One experimental paradigm for assessing aspects of executive control is requiring subjects to switch between two tasks. We evaluated a test in which such switching has previously been shown to involve activation of the medial and dorsolateral areas of the frontal cortex (DiGirolamo GJ et al. General and task-specific frontal lobe recruitment in older adults during executive processes: A fMRI investigation of task-switching. NeuroReport 2010, 12: 2065-2071). Methods: In this rule switching test (RST), strings of identical digits of varying length are presented on a computer screen (eg 888, 111111, 3333). In one condition, the subject has to determine whether the number of digits in each string is greater or smaller than 5, and in another condition whether the value of the digits is greater or smaller than 5. There are never 5 digits in the string and the digit 5 is not used. Each condition is associated with a particular colour which is presented before each string. The subject initially performs each condition separately in a block of 36 trials. Then in the “switching” phase, the subject is required to apply the rule according to the colour presented prior to each successive string; the colors being presented in an unpredictable sequence, forcing the subject to decide which rule to apply trial by trial. In the present study, 41 healthy volunteers aged 21 to 55 years performed the RST on three study days alongside Parts A and B of the trail making test (TMT). Part A of the TMT involves a single rule, while Part B involves rule switching. Analysis of variance was used to compare the performance between the various phases of the RST and correlations were run to establish test-retest reliability and examine relationships between the two tests and performance with the age of the volunteers. Further studies using the same methodology are underway using schizophrenic and bipolar patients. Results: In the RST, the subjects took significantly longer to respond in the switching phase than when performing the task using either one of the rules (p<0.001), this performance change reflecting the demands of rule switching and providing an assessment of executive control. The test-retest reliability of the speed scores in the switching and non-switching conditions of the RST was good (r=0.58 to 0.89), as was that for Parts A and B of the TMT (r=0.60 to 0.87). There were also statistically significant correlations between the RST switching condition and Part B of the TMT (r=0.37, p<0.02), as well as between the extra response time in the switching condition of the RST and the longer completion time of the TMT Part B (r=0.32, p<0.05). Further, the extra response time in the switching condition of the RST correlated with the age of the volunteers (r=0.5, p<0.001), indicating that the test is sensitive to age-related declines. Discussion: The RST appears to be suitable for repeatedly assessing executive control over time in clinical trials with volunteers. Early readouts of the data from follow up trials with schizophrenic and bipolar patients will be presented.