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.

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.

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.

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.

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.

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.

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.

Cognitive dysfunction in schizophrenia: comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs.

Impaired cognitive function is both a feature of schizophrenia and a side effect of conventional neuroleptics. Maze tests were used to determine the effects on cognition of conventional dopamine antagonist neuroleptics (haloperidol and fluphenazine) and the newer serotonin-dopamine antagonist antipsychotics (risperidone and clozapine). Patients on clozapine or risperidone showed better performance on the maze tasks than untreated patients or patients taking conventional neuroleptics. In particular, patients treated with risperidone or clozapine were better able to maintain motor coordination while they focused on the more complex "frontal" maze tasks which required sequencing and planning. In view of the restrictions on the use of clozapine, it is suggested that risperidone should be more widely used in schizophrenia because it preserves cognitive function better than conventional neuroleptics and is therefore likely to allow patients to have better insight into their illness and to have better long-term quality of life expectations.

The effects of sulpiride on psychomotor performance and subjective tolerance.

In many European countries, the substituted benzamide sulpiride is used with antidepressant indication in the dosage range of 150-300 mg on an outpatient population. This raises the concern of possible impairments of psychomotor performance in this dosage range. To address this question, the psychometric effects of 300 mg of sulpiride in comparison with placebo in 12 healthy volunteers was evaluated in this study. In a randomised, double-blind, two-way, within-subjects (cross-over) design, visuomotor performance was assessed using time estimation, critical flicker fusion, and choice reaction time tasks at baseline and 4 h after oral administration of either 300 mg of sulpiride or placebo. In addition, self-ratings on subjective well-being were obtained. Results were evaluated using analysis of covariance (ANCOVA) with baseline levels as covariates. In healthy subjects, 300 mg of sulpiride caused no alteration in time estimation and choice reaction movement time, whereas critical flicker fusion frequency was lower and choice-reaction decision time were prolonged under medication. Self-rating scales showed no significant differences between sulpiride and placebo. Subjects were not able to tell whether they received placebo or sulpiride. This study indicates that sulpiride is subjectively well tolerated at a dosage of 300 mg. However, using psychometric methods, effects are demonstrable that can be interpreted as a reduction of excitatory arousal without causing the subjective experience of sedation. These results call for caution when prescribing the drug to outpatients.

Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double-blind multicenter study, Austria.

In a double-blind, 4-week, prospective, randomized multicenter (17 centers) study we checked on the efficacy, tolerability and safety of moclobemide (300-600 mg/d) compared to imipramine (100-200 mg/d) in parallel groups of patients with a Major Depressive Episode (DSM III). The mean % reduction of the HAMD at the end of treatment was 51.7 in the moclobemide group and 52.1 in the imipramine group. The percentage of patients in whom efficacy was globally judged as "good" or "very good" was 62% in the moclobemide group and 60% in the imipramine group. There was no statistically significant difference in the efficacy in both groups but in some factors there was a trend for a better amelioration favoring moclobemide. The final overall physician's judgement of tolerability was "good" or "very good" in 83% of moclobemide patients and in 74% of imipramine patients. Adverse events were reported or observed in 56% of moclobemide patients and in 69% of imipramine patients. The number of mild, moderate and severe adverse events was higher in the imipramine group with a total of 286 versus 189. There was a statistically high significant difference considering the tolerability favoring moclobemide again. In this project the basic goal to find a substance with at least the same efficacy but a much better tolerability for sure got fulfilled.

Diagnosis and treatment of middle fossa arachnoid cysts and subdural hematomas.

Nine cases with temporal fossa arachnoid cysts were diagnosed by computerized tomography (CT). Five patients also had subdural hematomas, three of them following head trauma. When the hematoma was chronic and of equal hypodensity with the cyst, a clear-cut differentiation was not possible from the CT scan. The presence of a subdural hematoma could only be suggested by thickened arachnoid structures crossing the hypodense area, indicating the wall between cyst and hematoma. The cyst could often be diagnosed by bulging of the skull bone and a temporal lobe defect. Differences in density between cyst and hematoma, such as in subacute subdural hematoma, delineated both entities. Typical examples are demonstrated. Treatment consisted of evacuation of the hematoma and excision of the cyst in all cases.

Remoxipride versus haloperidol in healthy volunteers: psychometric performance and subjective tolerance profiles.

The aim of the present study was to evaluate the psychometric effects of equivalent clinical doses of remoxipride and haloperidol in comparison with placebo in healthy volunteers. In a double-blind design, either 3 mg haloperidol, 150 mg remoxipride, or placebo were administered to 36 healthy male volunteers ranging in age from 19 to 39 years. Performance was assessed using time estimation, critical flicker fusion, and choice reaction time tasks. In addition, self-ratings on subjective well-being were obtained. In healthy subjects, an acute dose of 3 mg haloperidol caused more severe alteration in cognitive functioning, cortical arousal, and psychomotor performance than a clinically equipotent dose of 150 mg remoxipride. Also, self-rating scales showed that subjective tolerance of remoxipride was partly superior to haloperidol. In general, the results of this study strongly suggest a difference between the psychometric profiles of remoxipride and haloperidol. This difference may be essential for maintaining a high level of compliance, especially in the long-term treatment of psychotic patients.

Cognitive function in schizophrenia.

Impaired cognitive function in schizophrenia, once thought to be a secondary effect of the psychosis, is now seen as an enduring and core feature. It has many manifestations, but the most disruptive element is arguably a fundamental defect in the patient's ability to manipulate available information. The magnitude of the cognitive deficit in schizophrenia is considerable and remains relatively stable despite fluctuations in other symptoms. The degree of dysfunction also has a high predictive value for long-term disability. In recent years, more attention has been directed towards cognitive dysfunction in schizophrenia as a result of which assessment scales and diagnostic systems increasingly incorporate cognitive dysfunction as an independent domain. Good cognitive function depends upon the brain's ability to prioritize tasks and to switch from parallel processing to sequential processing when the processing load is excessive. This requires working executive memory. Neuroimaging and functional analyses suggest that such cognitive function relies upon unimpaired prefrontal activity. In addition, there is increasing evidence that antipsychotic drugs with 5-hydroxytryptamine (5-HT)2A-blocking activity produce better cognitive function in patients with schizophrenia than drugs with predominantly dopamine (D)2-blocking activity (conventional neuroleptics). The development of sophisticated, computer-delivered maze tasks has shown that newer antipsychotics, such as clozapine and risperidone, differ from conventional neuroleptics in their effects on cognitive function. The prospects, therefore, are that patients treated with drugs having 5-HT2A-blocking activity will have better cognitive function and will be better able to function in life's roles than will patients treated with conventional neuroleptics.

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.

[Natural history and operative treatment of intracranial aneurysms after subarachnoid haemorrhage (author's transl)]. / Spontanverlauf und operative Behandlung intrakranieller Aneurysmen nach Subarachnoidalblutung.

This report presents an evaluation of prognosis in 227 patients with subarachnoid haemorrhage caused by intracranial aneurysm, comparing operative treatment in 118 patients with conservative treatment in 109. In all operable cases, the prognosis following early surgery was better than that of conservative treatment. Statistical comparison of patient groups according to the clinical condition allowed the formation of guidelines for the optimal timing of surgery: patients in good clinical condition should be operated on at the earliest possible moment. The overall mortality with such a policy is lower than with a waiting policy, since the majority of recurrences occurred within 2 weeks. Patients with disturbed consciousness and neurological deficit are best operated on either within 24 hours or following stabilization or improvement of the clinical picture -- mostly after 2 weeks. The risk of rebleeding is much lower in these cases, which justifies awaiting optimum clinical conditions. Surgery on comatose patients is contraindicated.

[Psychosocial aspects of epilepsy (author's transl)]. / Sozialpsychiatrische Aspekte der Epilepsie.

We tried to show the attitude of the environment towards the epileptic patient with special consideration of teachers and the mother of the epileptic child. specific problems of the epileptic patient like frequency of convulsions, psychiatric manifestations and the disease process itself were viewed in relationship to the ability to work and the position in school. We looked in addition into legal problems like fitness to drive, delinquency and insurance problems.

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.

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.

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.