Mirjam Rentrop

Intra-individual reaction time variability in schizophrenia, depression and borderline personality disorder

Intra-individual reaction time variability (IIV) in neuropsychological task performance reflects short term fluctuations in performance. Increased IIV has been reported in patients with schizophrenia and could be related to a deficient neural timing mechanism, but the role of IIV in adult patients with other psychiatric disorders has not been established. Therefore, we compared IIV measures obtained in a Go/Nogo task from patients with schizophrenia, major depression and borderline personality disorder. IIV was increased for patients with schizophrenia. When correcting for differences in mean reaction time, depressive and borderline patients also showed increased IIV. Importantly, all groups showed a strong association between IIV and accuracy of task performance. This suggests that increased IIV might be a sensitive marker for the efficiency of top-down attentional control in all diagnostic groups. Aside from these similarities, the complete results including measures of IIV, mean reaction time and accuracy show differential patterns for patients with schizophrenia compared to those with borderline personality disorder or depression. These results are discussed with respect to common versus disorder-specific neural mechanisms underlying increased IIV.

Response inhibition in borderline personality disorder: performance in a Go/Nogo task.

Background: Borderline personality disorder is associated with subtle neuropsychological deficits. A potential impairment of response inhibition is of major interest, since it could be related to impulsivity as a clinical feature of borderline personality disorder. Sampling and Methods: Response inhibition was studied in an auditory Go/Nogo paradigm in a sample of 20 female inpatients with borderline personality disorder and 18 healthy controls. The main measures of interest were general task performance, errors and reaction times. Results: Patients with borderline personality disorder performed worse in the Nogo task but not in the Go task. In the Nogo task, when response inhibition was essential, patients made more errors of commission, revealing problems to inhibit a prepotent response. Additionally, the borderline group was characterized by significantly shorter reaction times in both tasks compared to the nonclinical control group. The results for errors of commission in the Nogo task remained significant even after controlling for reaction time. Conclusions: The present results suggest a double impairment on this response inhibition task. First, borderline personality disorder patients have inadequately fast reaction times and a speed-accuracy tradeoff. Second, they show a genuine deficit of response inhibition. These results are discussed in the context of the conflicting literature on response inhibition and executive control in borderline personality disorder.

Intra-individual variability in high-functioning patients with schizophrenia.

Intra-individual variability of reaction times (IIV) can be employed as a measure of the stability of information processing, which has been proposed to be fundamentally disturbed in schizophrenia. However, the theoretical and clinical significance of IIV is not clear, in part because it has previously been investigated in subject groups with generalized cognitive impairment. Therefore, the purpose of the study was to assess IIV in high-functioning patients with schizophrenia and relatively preserved cognitive performance. 28 high-functioning patients with schizophrenia and 28 controls performed a Go/Nogo task and a Continuous Performance Test. In contrast to average measures of task performance, IIV differentiated consistently and with large effect size between groups. Modelling with an Ex-Gaussian distribution revealed that patients have a higher proportion of slow responses reflected by an increased tau parameter. The tau parameter was correlated with work capability in the sample with schizophrenia. In conclusion, IIV is an easily obtained measure, which is highly sensitive to fundamental cognitive deficits not directly visible in a high-functioning patient group. The response pattern with more exceedingly slow reactions could reflect a core deficit in the stability of information processing. The relationship with work capability suggests investigation of IIV as a clinical measure.

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

BackgroundThe 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.MethodsEighty-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.ResultsPlanning 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.ConclusionA 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.Trial registrationClinicalTrials.gov NCT00507988

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.

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.

Maintenance of real objects and their verbal designations in working memory

The present study investigated the neural correlates of working memory maintenance for real objects in contrast to their verbal designations. For this purpose we employed a delayed match-to-sample task using functional magnetic resonance imaging. The conjunction of load effects for objects and for words revealed a common bilateral network with main foci in the ventrolateral prefrontal cortex and the intraparietal sulcus. Load effect for objects in comparison to load effect for words revealed stronger activation of bilateral precuneus, which suggests the use of mental imagery of objects and object features. The opposite comparison load words versus load objects showed premotor and auditory areas to be activated in association with phonological rehearsal. The bilateral common activation indicates overlapping codes for real-world objects and their verbal designations. Importantly, there is also a dissociation between maintenance of words and objects, which indicates that phonological rehearsal and mental imagery are employed to different degrees.

Slow cortical potentials in human aversive trace conditioning.

The aim of the present study was to better understand the cortical structures and neuronal processes involved in aversive differential trace conditioning in healthy subjects. According to previous findings in literature, we tested whether the stimulus preceding negativity (SPN) in an emotional trace-conditioning paradigm shows a frontocentral maximum reflecting affective anticipation, e.g. in the anterior cingulate, or a centroparietal maximum reflecting time estimation and sensory anticipation. Two distinct SPN intervals were analyzed, one during the presentation of the CS (comparable to delay conditioning) and another one after CS offset (trace conditioning). In the CS+ condition, where subjects anticipated the onset of an aversive electrical stimulus after CS+ offset, a significantly larger negativity than in the unpaired (CS-) condition was present. SPN revealed a sustained midcentral and posterior parietal negativity during both SPN intervals. Differences between the two analyzed SPN intervals pointed towards occipital activity being found in the first interval (delay), but not in the second (trace). Aversive conditioning paradigms with longer trace intervals seem to rely upon a similar activation pattern as cognitive stimulus anticipation.

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.

TARGETING PLANNING AND PROBLEM SOLVING VERSUS BASIC COGNITION IN COGNITIVE REMEDIATION FOR PATIENTS WITH SCHIZOPHRENIA

Cognitive deficits are important predictors of functional outcome in patients with schizophrenia. Approaches to psychological treatment of cognitive deficits have been subsumed under the term cognitive remediation. There is now converging evidence that cognitive remediation has moderate effects on cognitive performance (McGurk et al., 2007). Importantly, these improvements can generalize to functional outcome, particularly when cognitive remediation is combined with comprehensive rehabilitation. When addressing the question which cognitive functions to target, a major goal is an effect on functional outcome. While an influence of basic cognition on functional outcome has been established, it has been suggested that at least part of this effect is mediated by intermediate functions such as social cognition or learning ability (Green et al., 2000; Vauth et al., 2004). These potential mediators have been proposed as potential targets for training interventions in contrast to the “traditional” training of basic cognition. One cognitive domain of potential clinical relevance is planning and problem-solving (Medalia et al., 2001), which requires the integration of basic cognitive functions. This capacity has been shown to be closely associated with functional outcome.