Cognitive deficits in schizophrenia – specific patterns, neural correlates and remediation through training

Research on cognition in people with schizophrenia has provoked a lot of interest for two reasons: It offers a better understanding of the neurobiological components of the disorder and it helps creating effective treatments for cognitive deficits, which limit the possible functional outcome after remission. The three studies presented here are all concerned with cognitive deficits in schizophrenia, but they focus on different levels, from electrophysiology to work ability in a clinical setting. The first two studies addressed the question of an underlying core deficit of the disorder, which might lead to the clinical features of the illness, in particular the commonly observed broad cognitive impairments. In both studies we hypothesized that increased intra-individual variability could be found in a high-functioning sample of patients with schizophrenia. The first study concentrated on response times whereas the second used an electrophysiological measure. The third study directly compared two cognitive trainings which work on different levels – one working with basic cognitive functions like memory and attention and one specifically training planning and problem solving as a part of higher cognitive functioning. The first study did not only find increased intra-individual variability in high-functioning patients with schizophrenia but could show an association between increased variability of response times and poorer work ability. The second study found that on an electrophysiological level increased temporal variability was found when analysing single trials of the N2 component, and that higher variability was linked with a more widespread activation during the N2 time-window. The third study comparing the two trainings did not find a clear advantage of one over the other. Both trainings lead to some improvements in cognitive functioning and work ability. There was an indication that planning ability improved more when trained directly instead of being trained via basic cognitive abilities. The first two studies emphasize the importance of intra-individual variability for schizophrenia and its occurrence on different levels. The association between response variability and work ability further highlights the importance of this measure. The third study indicates that a new training focussing specifically on planning and problem solving had an effect comparable to that of a more conventional training for patients with schizophrenia. Its results show how important it is to directly compare different kinds of training with each other and with a control group. In conjunction, the three studies provide the basis for further research into putative cognitive and neurophysiological core deficits of schizophrenia, which could provide a theoretical basis for the development of cognitive training programs

The Plan-a-Day Approach to Measuring Planning Ability in Patients with Schizophrenia

Deficits in executive functioning are closely related to the level of everyday functioning in patients with schizophrenia. However, many existing neuropsychological measures are limited in their ability to predict functional outcome. To contribute towards closing this gap, we developed a computer-based test of planning ability ("Plan-a-Day”) that requires participants to create daily activity schedules in a simulated work setting. Eighty patients diagnosed with schizophrenia were tested with Plan-a-Day and a battery of cognitive ability tests. Plan-a-Day showed satisfactory psychometric properties in terms of consistency, reliability, and construct validity. Compared to other neuropsychological tests used in this study, it also demonstrated incremental validity with regard to the Global Assessment of Functioning. The Plan-a-Day approach, therefore, seems to represent a valid alternative for measuring planning ability in patients with executive function deficits, occupying a middle ground between traditional neuropsychological tests and real-life assessments. (JINS, 2011, 17, 327-335

Predictors for Improvement of Problem-Solving during Cognitive Remediation for Patients with Schizophrenia

Cognitive remediation is a promising pathway for ameliorating cognitive impairment of patients with schizophrenia. Here, we investigate predictors of improvement in problem-solving ability for two different types of cognitive remediation - specific problem-solving training and training of basic cognition. For this purpose we conducted a re-analysis of a randomized controlled trial comparing these two training approaches. The main outcome measure was improvement in problem-solving performance. Correlational analyses were used to assess the contribution of clinical, cognitive and training-related predictors. In the problem-solving training group, impaired pre-training planning ability was associated with stronger improvement. In contrast, in the basic cognition training group antipsychotic medication dose emerged as a negative predictor. These results demonstrate that predictors for successful cognitive remediation depend on the specific intervention. Furthermore, our results suggest that at least in the planning domain patients with impaired performance benefit particularly from a specific intervention. (JINS, 2014, 20, 1-6

Intraindividual variability in inhibitory function in adults with ADHD - an ex-Gaussian approach

OBJECTIVE: Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses. METHODS: Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. RESULTS: We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. CONCLUSIONS: Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD

Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial

BACKGROUND: The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. METHODS: Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. RESULTS: Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. CONCLUSION: A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings

Temporal variability and spatial diffusion of the N2 event-related potential in high-functioning patients with schizophrenia

Recent theories of schizophrenia have proposed a fundamental instability of information processing on a neurophysiological level, which can be measured as an increase in latency variability of event-related potentials (ERPs). If this reflects a fundamental deficit of the schizophrenic illness, it should also occur in high-functioning patients. These patients have also been observed to show a more diffuse activation pattern in neuroimaging studies, which is thought to reflect compensatory processes to maintain task performance. In the present study we investigated temporal variability and spatial diffusion of the visual N2 component in a group of high-functioning patients with preserved cognitive performance. 28 patients with schizophrenia and 28 control participants matched for gender, age and education participated in the study. Subjects performed a visual Go/Nogo task, while event-related potentials were obtained. Trial-to-trial latency variability was calculated with a Wavelet-based method. Patients with schizophrenia showed a robust increase in N2 latency variability at electrodes Fz and Cz in all task conditions. Regarding spatial distribution healthy participants showed a focused fronto-central N2 peak. In contrast, patients with schizophrenia showed a more diffuse pattern and additional negative peaks over lateral electrodes in the Nogo condition. These results clearly show that even in high-functioning patients with schizophrenia a higher temporal variability of ERPs can be observed. This provides support for temporal instability of information processing as a fundamental deficit associated with schizophrenia. The more diffuse scalp distribution might reflect processes that compensate for this instability when cognitive control is required

The Plan-a-Day approach to measuring planning ability in patients with schizophrenia

Deficits in executive functioning are closely related to the level of everyday functioning in patients with schizophrenia. However, many existing neuropsychological measures are limited in their ability to predict functional outcome. To contribute towards closing this gap, we developed a computer-based test of planning ability ("Plan-a-Day") that requires participants to create daily activity schedules in a simulated work setting. Eighty patients diagnosed with schizophrenia were tested with Plan-a-Day and a battery of cognitive ability tests. Plan-a-Day showed satisfactory psychometric properties in terms of consistency, reliability, and construct validity. Compared to other neuropsychological tests used in this study, it also demonstrated incremental validity with regard to the Global Assessment of Functioning. The Plan-a-Day approach, therefore, seems to represent a valid alternative for measuring planning ability in patients with executive function deficits, occupying a middle ground between traditional neuropsychological tests and real-life assessments