Temporal unpredictability of a stimulus sequence and the processing of neutral and emotional stimuli.

Most experimental settings in cognitive neuroscience present a temporally structured stimulus sequence, i.e., stimuli may occur at either constant and predictable or variable and less predictable inter-stimulus intervals (ISIs). This experimental feature has been shown to affect behavior and activation of various cerebral structures such as the parietal cortex and the amygdala. Studies employing explicit or implicit cues to manipulate predictability of events have shown that unpredictability particularly accentuates the response to events of negative valence. The present study investigates whether the effects of unpredictability are similarly affected by the emotional content of stimuli when unpredictability is induced simply by the temporal structure of a stimulus sequence, i.e., by variable as compared to constant ISIs. In an fMRI study, we applied three choice-reaction-time tasks with stimuli of different social-emotional content. Subjects (N=30) were asked to identify the gender in angry and happy faces, or the shape of geometric figures. Tasks were performed with variable and constant ISIs. During the identification of shapes, variable ISIs increased activation in widespread areas comprising the amygdala and fronto-parietal regions. Conversely, variable ISIs during gender identification resulted in a decrease of activation in a small region near the intraparietal sulcus. Our findings reveal that variability in the temporal stimulus structure of an experimental setting affects cerebral activation depending on task demands. They suggest that the processing of emotional stimuli of different valence is not much affected by the decision of employing a constant or a variable temporal stimulus structure, at least in the context of implicit emotion processing tasks. In contrast, temporal structure diversely affects the processing of neutral non-social compared to emotional stimuli, emphasizing the relevance of considering this experimental feature in studies which aim at differentiating social-emotional from cognitive processing in general, and more particularly, aim at identifying circumscribed alterations of social cognition in mental disorders.

The significance of caudate volume for age-related associative memory decline.

Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain.

Illness perceptions and personality traits of patients with mental disorders: the impact of ethnicity.

OBJECTIVE: To identify differences and similarities between immigrants of Turkish origin and native German patients in therapeutically relevant dimensions such as subjective illness perceptions and personality traits. METHOD: Turkish and native German mentally disordered in-patients were interviewed in three psychiatric clinics in Hessen, Germany. The Revised Illness Perception Questionnaire (IPQ-Revised) and the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) were used. Differences of scales and similarities by k-means cluster analyses were estimated. RESULTS: Of the 362 total patients, 227 (123 immigrants and 104 native Germans) were included. Neither demographic nor clinical differences were detected. Socioeconomic gradients and differences on IPQ-R scales were identified. For each ethnicity, the cluster analysis identified four different patient types based on NEO-FFI and IPQ-R scales. The patient types of each ethnicity appeared to be very similar in their structure, but they differed solely in the magnitude of the cluster means on included subscales according to ethnicity. CONCLUSION: When subjective illness perceptions and personality traits are considered together, basic patient types emerge independent of the ethnicity. Thus, the ethnical impact on patient types diminishes and a convergence was detected.

Reduced sensitivity to emotional facial expressions in borderline personality disorder: effects of emotional valence and intensity.

A heightened sensitivity towards negative emotional stimuli has been described for Borderline Personality Disorder (BPD). We investigated whether a faster and more accurate detection of negatively valent information in BPD can be confirmed by means of a visual search task which required subjects to detect a face with an incongruent emotional expression within a crowd of neutral faces. Twenty eight BPD patients and 28 nonpatients were asked to indicate whether a set of schematic neutral faces (3 × 3, 4 × 4 matrices) contained a happy or an angry face. Besides valence, the intensity of the target's emotion was varied in two steps. BPD patients and nonpatients both demonstrated an anger-superiority effect. However, no higher sensitivity towards negative stimuli was observed in BPD compared to nonpatients. BPD patients seem to rely to a stronger extent on controlled, i.e., serial, attention demanding processes when searching more subtle social-emotional information with positive valence.

Influences on therapist's decisions for neuroleptic treatment in schizophrenia: the role of characteristics of the patient and the physician.

We investigated factors influencing physicians' treatment decisions regarding 4 antipsychotic treatment strategies for schizophrenia (conventional oral/conventional depot/atypical oral/atypical depot). We analysed the influence of the patient's compliance with medication, socio-economic status (occupational prestige/educational attainment), as well as the influence of gender, age and practice setting (psychiatric/general hospital/private practice) of the prescribing physician.We examined the influence of these factors by means of case vignettes. 4 vignettes were constructed with varying levels for compliance and socio-economic status. For each vignette, physicians had to choose one treatment strategy from the 4 alternatives. Data were collected using a survey (n=1 342) of physicians in Germany and analysed using a weighted least-squares regression model and a random-effect logit model.Compliance and status had interactive effects on treatment selection. Low compliance was associated with an increase in selections of depot medication. For high-status, noncompliant patients, physicians selected mainly atypical oral and atypical depot antipsychotics. Low-status, noncompliant patients were mostly given conventional and atypical depot antipsychotics. Noncompliant, low-status patients received conventional depot antipsychotics 4 times as often as noncompliant, high-status patients. The physician's age and practice setting were also related to the treatment selection.Therapeutic decisions are influenced by patients' and the physicians' characteristics. There might be barriers for patients with low compliance and low socio-economic status that prevent them from being prescribed newer medications. Not all physicians seem to have the same choices of treatment options available to them.

Depressive and aggressive responses to frustration: development of a questionnaire and its validation in a sample of male alcoholics.

Since clinical and biochemical observations point to much overlap between depression and aggression, both characterised by intolerance to frustration, a questionnaire was developed to test if different patterns of depressive and aggressive reactions elicited by exposure to negative events and deprivation from expected positive ones in human and nonhuman conditions, respectively, would result in specific response patterns in depressive and aggressive persons. The questionnaire was tested for internal consistency in a pilot healthy sample and for correlations of responses with the personality factors of Aggression and Depression in 60 abstinent male alcoholics. Aggressive and depressive responses were highly correlated across all stimulus conditions, and not specifically but rather equally associated with the personality factors of Aggression and Depression, confirming the close association between these dimensions.

Objective measurement of motor activity during cognitive performance in adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigates whether hyperactivity, i.e. an increased level of motor activity, can be observed in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: An infrared motion-tracking system was used to measure motor activity in 20 unmedicated adults with ADHD and 20 matched healthy controls (HC) during a 1-back working memory task. RESULTS: Motor activity was higher in ADHD. It increased with the duration of testing and co-varied with cognitive performance in ADHD only. Subjective and objective measurements of motor activity were related in HC, but not in ADHD. CONCLUSION: Higher levels of motor activity in ADHD are objectively measurable not only in children, but in adults as well. It is linked to cognitive performance arguing against distinguishable diagnostic subtypes. The objective measurement of motor activity seems to extend the description of ADHD symptoms derived from rating scales and might thus help to bridge the gap between psychopathological symptom description and neurobiological alterations.

Neuronal correlates of affective theory of mind in schizophrenia out-patients: evidence for a baseline deficit.

BACKGROUND: Schizophrenia out-patients have deficits in affective theory of mind (ToM) but also on more basal levels of social cognition, such as the processing of neutral and emotional expressions. These deficits are associated with changes in brain activation in the amygdala and the superior temporal sulcus (STS). However, until now there have been no studies that examined these different levels of social cognition and their neurobiological underpinnings in patients within one design. METHOD: Sixteen medicated schizophrenia out-patients and 16 matched healthy controls were studied with functional magnetic resonance imaging (fMRI) during a social cognition task that allows the investigation of affective ToM (aToM), emotion recognition and the processing of neutral facial expressions. RESULTS: Patients showed a deficit in emotion recognition and a more prominent deficit in aToM. The performance in aToM and in emotion recognition was correlated in the control group but not in the schizophrenia group. Region-of-interest analysis of functional brain imaging data revealed no difference between groups during aToM, but a hyperactivation in the schizophrenia group in the left amygdala and right STS during emotion recognition and the processing of neutral facial expressions. CONCLUSIONS: The results indicate that schizophrenia out-patients have deficits at several levels of social cognition and provide the first evidence that deficits on higher-order social cognitive processes in schizophrenia may be traced back to an aberrant processing of faces per se.

A functional variant of the tryptophan hydroxylase 2 gene impacts working memory: a genetic imaging study.

Imaging studies have demonstrated that prefrontal and parietal regions are activated during working memory (WM) tasks. Recently some molecular genetic studies reported associations between a functional promoter polymorphism of the tryptophan hydroxylase 2 gene (TPH2), that regulates the synthesis of serotonin, and attention. In 49 healthy Caucasian subjects the role of the TPH2 -703 G/T polymorphism for WM was tested by means of an imaging genomics approach in an n-back task. fMRI data showed an increased activation for the 2-back as compared to the 0-back condition for a large network in prefrontal and parietal areas. Although behavioural data showed no performance differences between the genotype groups of the -703 G/T a significantly stronger activation of the TT genotype carriers in BA 6, BA 46, and BA 40 was visible in contrast to the GT and GG groups. Present findings in congruence with previous findings support the hypothesis that TT carriers compensate deficits in executive control functions by increased brain activity.

Course of recovery of cognitive impairment in patients with schizophrenia: a randomised double-blind study comparing sertindole and haloperidol.

OBJECTIVE: To compare the impact of sertindole and haloperidol on cognitive function in patients suffering from schizophrenia. METHODS: In a 12 week trial, of the 40 patients randomised to treatment, 34 (17 sertindole and 17 haloperidol) were included in the analysis set. Cognitive sub-processes were investigated with the Reaction Time Decomposition (RTD) method and the Wisconsin Card Sorting Test (WCST), at baseline, Week 4 and Week 12. RESULTS: In executive function, i.e. set shifting tasks, sertindole reversed cognitive deficits significantly more than haloperidol. It was demonstrated that this atypical drug improved cognitive processing independently of motor function. Patients receiving sertindole markedly improved on the RTD task at Week 4 and continued to improve (although at a slower rate) at Week 12, those patients receiving haloperidol showed marked impairment at Week 4 with partial recovery by Week 12. CONCLUSION: The study demonstrated two distinct processes of action on cognition between sertindole and haloperidol and the marked beneficial effects of sertindole, particularly in parameters that are regarded as schizophrenia-related cognitive disturbances.

The influence of antipsychotic treatment on brain reward system reactivity in schizophrenia patients.

INTRODUCTION: Neuroleptic dysphoria is discussed as a serious side effect of antipsychotic medication. One aspect of this condition, a reduced motivation to reach potential rewards, might be induced by a blockade of striatal D2 receptors resulting in a reduced reactivity of the brain reward system. However, since this D2 antagonistic effect is higher for typical than atypical antipsychotics, typical antipsychotics should induce a stronger dampening of brain reward system activation. This hypothesis was tested in an event related functional magnetic resonance imaging study. METHODS: A monetary reward paradigm was presented to 30 schizophrenia patients, who were treated with typical or atypical antipsychotics or a combination of both. Hemodynamic responses were analyzed during the anticipation and the reception of the reward. RESULTS: Activation of the right ventral striatum, a core region of the brain reward system, was lower in patients treated with typical antipsychotics but only during the anticipation and not the delivery of a monetary reward. DISCUSSION: This result indicates that a D2 associated reduction of brain reward system reactivity might be the neurobiological correlate of reduced motivation observed in the context of neuroleptic dysphoria. Using typical antipsychotics might worsen this effect, increasing the negative symptomatology of schizophrenia patients.

Cognitive subprocesses and schizophrenia. A. Reaction-time decomposition.

OBJECTIVE: The aim of the study is to demonstrate that deficits of information processing in schizophrenic patients can be isolated with reaction-time (RT) decomposition paradigms. METHOD: Three types of visually presented tasks were applied: simple, disjunctive and choice RT-tasks. RT were split into movement latency and time necessary to execute movements. Comparisons of three samples of schizophrenic patients (295.3) with individually matched (age, sex. education and handedness) healthy controls are presented: Sample 1: 10 drug-naive first-onset patients, Sample 2: 10 neuroleptically treated first-onset patients, Sample 3: 10 neuroleptically treated chronically ill patients. RESULTS: Findings indicate that schizophrenia affects primarily subprocesses in which percepts are translated into appropriate actions (response-selection). Neuroleptic treatment improves processing at this stage but is accompanied by slowing of movement execution. CONCLUSION: Response-selection is selectively impaired in first-onset patients. This disturbance, which might be specific for schizophrenia, can be regarded as indication of a disconnection between frontal and posterior areas.

Cognitive subprocesses and schizophrenia. B. Maze tasks.

OBJECTIVE: In a companion paper we demonstrated that in reaction-time tasks the response selection stage is selectively disturbed in schizophrenia. The aim of the present study is the investigation of subprocesses, which are incorporated into repeatedly activated loops of cognitive processes and need additional information from working memory. METHOD: Maze tasks of varying complexity (with and without bifurcations) were presented to drug-naive and treated first-onset schizophrenic patients. The tasks had to be solved under easy and difficult motor-conditions. Both patient samples were compared with healthy control groups matched by age, sex, education and experience with the experimental setting. RESULTS: In mazes with alternative routes patients exhibited the expected decrease of performance. However, untreated patients improved under difficult motor conditions. This improvement is smaller after neuroleptic treatment. CONCLUSION: Under difficult motor conditions attention is focused on the execution of movements and thus withdrawn from perceiving irrelevant response alternatives, i.e. the effects of disturbed response selection are reduced.

Reaction-times and bioelectrical brain signals of drug-naive schizophrenic first-onset patients in identification and classification tasks.

OBJECTIVE: The question of the present study is whether disturbances of response-selection in schizophrenic patients are discernible only if overt motor-actions are required, or also if covert cognitive actions are necessary. METHOD: Visual identification (digits) and classification (dot-enumeration) tasks were presented to 18 drug-naive, first-onset schizophrenic patients and healthy controls. It is assumed that enumeration of more than three dots requires additional cognitive processes as buffering and re-focusing of attention. Reaction-times and 21-channel-EEG were measured. For eye-movement artefact-elimination a new non-parametric regression approach was applied. RESULTS: Reaction-times revealed that in the patient group response selection is lengthened in both tasks. Perception of dot numbers is not affected. Bioelectrical data depicted a left-lateralization of posterior P100 and N 100 in the patient group as well as an enhanced fronto-central P200. CONCLUSION: Whereas in reaction-times of patients only a disturbance of response selection is discernible, bioelectrical measurements also point to an altered organization of perceptive processes.

Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study.

In Germany, clomethiazole (CLO) and benzodiazepines are predominantly used as therapeutic agents in the treatment of the alcohol withdrawal syndrome (AWS). These agents have disadvantages such as sedation, risk of respiratory insufficiency, and cardiovascular complications as well as addictive potential. Alternatively, it could be demonstrated that both tiapride (TIA) and carbamazepine (CBZ) are efficient in the treatment of AWS with less toxicity. However, they seem to be less effective in AWS than CLO as single agents. But no systematic comparison of the combination of TIA and CBZ against an established therapeutic standard can be found in the literature. Therefore, we compared the combination of TIA and CBZ with CLO in two open exploratory studies with matched samples. Outcome parameters were heart rate, blood pressure, complications, withdrawal symptoms (CIWA-Ar scale), and general clinical state (CGI scale). A retrospective evaluation of medical records (30 TIA+CBZ, 30 CLO) was followed by an open prospective study (40 TIA+CBZ, 40 CLO). Both studies revealed similar efficacy in terms of psychopathologic and vegetative symptoms. Vegetative recovery seems to be faster with TIA+CBZ. Results of this exploratory study have to be confirmed by a controlled double-blind study with severity of AWS as an experimental factor.

Responsiveness of subjective quality of life assessment in schizophrenic patients: a quasi-experimental pilot study.

Responsiveness of quality of life (QOL) assessments in chronic schizophrenic patients was investigated by a quasi-experimental pilot study. Satisfaction ratings were assessed over five time points with an externally imposed disturbing stimulus at the second time point. Despite a markedly high stability, the disturbance provoked a temporally limited decrease in QOL.

The importance of social comparisons for high levels of subjective quality of life in chronic schizophrenic patients.

In schizophrenic patients, quality of life (QoL) studies often find high levels of general life satisfaction and satisfaction in various life domains despite deprived living conditions. Therefore, the usefulness of QoL as an outcome indicator has been questioned. Since social comparison processes have been postulated to be related to the level of satisfaction, this hypothesis was analysed empirically by the present study in schizophrenic patients. Satisfaction and social comparisons of 148 schizophrenic inpatients and 66 mentally healthy controls were examined with regard to the domains 'health' and 'family' by means of a standardised interview. The schizophrenic patients had a history of either long-term (n = 75) or short-term (n = 73) restricted and deprived living conditions. Long-term patients showed significantly higher satisfaction levels than short-term patients. They compared themselves predominantly laterally or downwards with fellow inpatients. Significant relationships between the direction of social comparisons and satisfaction ratings were found in all three samples. Social comparisons proved to be important for the level of satisfaction in schizophrenic patients. Results indicate that experiences of restricted and deprived living conditions induce accommodation processes and response-shifts that should be taken into account in the interpretation of quality-of-life data.

Cognitive dysfunction in schizophrenia: a new set of tools for the assessment of cognition and drug effects.

Cognitive impairment in schizophrenia must be seen as a disturbance of cortico-sub-cortical connectivity with a neurotransmitter imbalance in a circuitry system, which connects thalamic input with prefrontal processing and supplementary motor cortex and basal ganglia output. The concept of maze-solving behaviour as a continuous cognitive task evoking a conflict between prefrontal cortex and basal ganglia activity is explained and introduced to distinguish between the effects of D2 blocking agents and substances with a predominant 5HT2A receptor affinity, such as clozapine and risperidone. Complex mazes show a cognitive deficit in untreated schizophrenic patients that are impaired by conventional and improved by atypical antipsychotic substances. Processing speed improves most on clozapine, while parallel processing is best supported by the non-sedative atypical substance risperidone. Maze paradigms are presented.

The topography of non-linear cortical dynamics at rest, in mental calculation and moving shape perception.

Differential cortical activation by cognitive processing was studied using dimensional complexity, a measure derived from nonlinear dynamics that indicates the degrees of freedom (complexity) of a dynamic system. We examined the EEG of 32 healthy subjects at rest, during a visually presented calculation task, and during a moving shape perception task. As a nonlinear measure of connectivity, the mutual dimension of selected electrode pairs was used. The first Lyapunov coefficient was also calculated. Data were tested for non-linearity using a surrogate data method and compared to spectral EEG measures (power, coherence). Surrogate data testing confirmed the presence of nonlinear structure in the data. Cognitive activation led to a highly significant rise in dimensional complexity. While both tasks activated central, parietal and temporal areas, mental arithmetic showed frontal activation and an activity maximum at T3, while the moving shape task led to occipital activation and a right parietal activity maximum. Analysis of mutual dimension showed activation of a bilateral temporal-right frontal network in calculation. The Lyapunov coefficient showed clear topographic variation, but was not significantly changed by mental tasks (p<.09). While dimensional complexity was almost unrelated to power values, nonlinear (mutual dimension) and linear (coherence) measures of connectivity shared up to 37% of variance. Data are interpreted in terms of increased cortical complexity as a result of recruitment of asynchronously active, distributed neuronal assemblies in cognition. The topography of nonlinear dynamics are related to neuropsychological and neuroimaging findings on mental calculation and moving shape perception.