Harald Gruppe

Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans

In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.

Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole.

Abstract 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.

Brain Activation during Mental Maze Solving

Background: So-called Porteus mazes are used to investigate prefrontal cortex (PFC) functioning in normal subjects and patients with different neuropsychiatric disorders. Here we present data confirming the involvement of the PFC for the first time by means of functional magnetic resonance imaging (fMRI). To minimize motor-related activation, mental mazes were used. Methods: Mazes as well as pseudo-mazes without any bifurcations were presented to 49 healthy participants during fMRI scans. Results: Both, mazes as well as pseudo-mazes, activated a large network from visual to parietal regions, reflecting the dorsal stream of visual information processing. Mazes but not pseudo-mazes also activated bilateral areas of the PFC indicating their special role in decision processes. In addition, although no motor response was required during maze performance, both tasks activated subcortical and cortical motor areas. Conclusions: These tasks are suitable for investigating and specifying PFC functioning and its impairment in psychiatric disorders such as schizophrenia. In addition, mental mazes might be a suitable task for the investigation of patients with motor disturbances.

Modifikation und Anwendung der Münchner Lebensqualitäts-Dimensionen-Liste bei schizophrenen Patienten

Fur die Evaluation einer Versorgungsstruktur schizophrener Patienten wurde ein Inventar zur Lebensqualitat gesucht, das zusammen mit weiteren Beurteilungsverfahren eingesetzt werden kann, ohne die Patienten durch die Dauer der Untersuchung zu uberfordern. Es sollte ein umfassendes Profil der subjektiven Lebensqualitat erfassen, praktikabel sein und befriedigende psychometrische Gutekriterien aufweisen (Bullinger und Poppel, 1988). Das Instrument sollte bereits durch die Art der Konstruktion einen konsequent subjektiven Ansatz verfolgen, da objektive Indikatoren der Lebensqualitat bestenfalls bescheidene Beziehungen zur Lebenszufriedenheit hervorbringen und bei Probanden mit atypischem Lebensstil — wie z.B. chronisch psychisch Kranken — noch unzulanglicher sind (Lehman, 1983).

Temporal unpredictability of a stimulus sequence affects brain activation differently depending on cognitive task demands

Within cognitive neuroscience, in nearly every experimental setting, subjects are presented with stimuli that appear at either constant or variable points in time, referred to as interstimulus intervals (ISIs). These temporal patterns differ in the degree to which an exact stimulus onset may be predicted. We investigated whether this experimental feature affects brain and behavior, and whether the impact is modulated by the cognitive demands of a task. Subjects (N=26) were assessed via fMRI while solving three different tasks under either temporally predictable (constant ISI) or unpredictable (variable ISI) conditions. The tasks differed with regard to demands on working memory and response uncertainty. Compared to constant ISIs, variable (i.e., less predictable) ISIs led to a general increase in reaction time and in right amygdala activation. Depending on the cognitive demands required by the specific task, the left amygdala, the parietal cortex, the supplementary motor area, and the dorsolateral prefrontal cortex were engaged as well. The results indicate that the temporal structure in a stimulus sequence affects both overt and covert behaviors. Implicit temporal uncertainty increases activation in several brain regions depending on cognitive demands. Thus, an often-overlooked basic design feature, the application of constant or variable ISIs, may contribute to heterogeneity in cognitive neuroscience findings.

Hemodynamic response pattern of spatial cueing is different for social and symbolic cues

Directional social gaze and symbolic arrow cues both serve as spatial cues, causing seemingly reflexive shifts of an observer’s attention. However, the underlying neural substrates remain a point at issue. The present study specifically addressed the differences in the activation patterns associated with non-predictive gaze and arrow cues, placing special emphasis on brain regions known to be involved in the processing of social information [superior temporal sulcus (STS), fusiform gyrus (FFG)]. Additionally, the functional connectivity of these brain regions with other areas involved in gaze processing and spatial attention was investigated. Results indicate that gaze and arrow cues recruit several brain regions differently, with gaze cues increasing activation in occipito-temporal regions and arrow cues increasing activation in occipito-parietal regions. Specifically, gaze cues in contrast to arrow cues enhanced activation in the FFG and the STS. Functional connectivity analysis revealed that during gaze cueing the STS was more strongly connected to the intraparietal sulcus (IPS) and the frontal eye fields, whereas the FFG was more strongly connected to the IPS and the amygdala.

Validation of the German Version of the Social Functioning Scale (SFS) for Schizophrenia

Deficits in social functioning are a core symptom of schizophrenia and an important criterion for evaluating the success of treatment. However, there is little agreement regarding its measurement. A common, often cited instrument for assessing self-reported social functioning is the Social Functioning Scale (SFS). The study aimed to investigate the reliability and validity of the German translation. 101 patients suffering from schizophrenia (SZ) and 101 matched controls (C) (60 male / 41 female, 35.8 years in both groups) completed the German version. In addition, demographic, clinical, and functional data were collected. Internal consistency was investigated calculating Cronbach’s alpha for SFS full scale (α: .81) and all subscales (α: .59-.88). Significant bivariate correlation coefficients were found between all subscales as well as between all subscales and full scale (p <.01). For the total sample, principal component analysis gave evidence to prefer a single-factor solution (eigenvalue ≥ 1) accounting for 48.5 % of the variance. For the subsamples, a two-component solution (SZ; 57.0 %) and a three-component solution (C; 65.6 %) fitted best, respectively. For SZ and C, significant associations were found between SFS and external criteria. The main factor “group” emerged as being significant. C showed higher values on both subscales and full scale. The sensitivity of the SFS was examined using discriminant analysis. 86.5% of the participants could be categorized correctly to their actual group. The German translation of the SFS turned out to be a reliable and valid questionnaire comparable to the original English version. This is in line with Spanish and Norwegian translations of the SFS. Concluding, the German version of the SFS is well suited to become a useful and practicable instrument for the assessment of social functioning in both clinical practice and research. It accomplishes commonly used external assessment scales.

Influence of Vigilance and Learning on Prefrontal Activation in Schizophrenia

Background: Executive functions, which are neuroanatomically associated with the frontal lobe, are known to be impaired in schizophrenia. It is, however, still unclear whether the underlying functional disturbance is due to a hyper- or a hypoactivation of the dorsolateral prefrontal cortex (DLPFC) or neither. Methods: To address this question, we examined the brain activation of 21 schizophrenic patients on atypical antipsychotic medication and 21 healthy control subjects during a mental maze task by means of fMRI. Results: We found no significant overall difference in cerebral activation between the groups, but differences in the change in DLPFC activation from the first to the second half of the experiment. In the maze compared to the control task, there was a decrease in activation in the DLPFC in the patients and an almost significant increase in the controls. The change in activation in the patient group correlated with a change in subjective sleepiness, while the increase in activation in the controls could be attributed to learning processes. Conclusion: We hypothesized that differential temporal influences on brain activation could lead to either hyper- or hypoactivation of the DLPFC in schizophrenia.

Neuromodulatorische Einflüsse auf das Wohlbefinden: Dopamin und Oxytocin

Nahert man sich dem Phanomen des Wohlbefindens aus neurobiologischer Sicht, so stellt sich das Problem, dass es sich bei Wohlbefinden um einen subjektiven Zustand handelt. Diese subjektive Qualitat macht die Erforschung und Beschreibung der neurobiologischen und neurochemischen Grundlagen schwierig. Daruber hinaus ist Wohlbefinden eine Form affektiven Erlebens, die vom Gesamtzustand des Individuums beeinflusst wird. Aufgrund der subjektiven Erlebnisqualitat und globalen Determiniertheit des Phanomens kann davon ausgegangen werden, dass die korperlichen und psychologischen Einflussfaktoren auf das Wohlbefinden, respektive sein Fehlen, auserst vielfaltig sind. Eine Annaherung an die neurobiologischen Grundlagen erfordert daher zunachst eine Reduzierung auf allgemeine Prinzipien, die dem Wohlbefinden als subjektiver Erlebensqualitat zugrunde liegen. Relevante Aspekte mussen dann gegenuber ahnlichen Konstrukten abgegrenzt und operationalisiert, d. h. experimentell manipulierbar und messbar gemacht werden.

Psychophysiology, psychoneuroendocrinology, and the laterality concept of the brain

Twenty-two patients--11 paranoid schizophrenics and 11 major depressed--were investigated by means of a hypothalamic-pituitary challenge (HPC). The latter contained insulin, TRH and metoclopramide. Response with regard to blood glucose, serum GH, PRL, TSH and cortisol were measured 30, 60, 90, 120 and 180 min after the baseline. Temporal alpha power was split into 2 groups with high and low alpha power, respectively. The aim was to see whether high cortical-limbic-hypothalamic-pituitary and hypothalamic-pituitary-adrenal reactivity correlated with high temporal alpha power. Poor results were found with regard to diagnoses. Only TSH and glucose response were correlated with diagnoses. But, GH and cortisol responses reacted in relation to different alpha levels. Cell loss due to hormonal stress and consecutive miswiring of axons due to wrong sprouting are discussed as possible reasons for abnormal lateralized HPC response.