Bernd Gallhofer

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.

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 patients 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 brains 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-HTM2A -blocking activity will have better cognitive function and will be better able to function in lifes roles than will patients treated with conventional neuroleptics.

Imaging gene–substance interactions: The effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea.

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age‐, sex‐ and education‐matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n‐back tasks were applied embedded in a reaction‐time‐decomposition approach. Deficits in n‐back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1‐back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2‐back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross‐group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.

Neuronal Correlates of Social Cognition in Borderline Personality Disorder

Patients with borderline personality disorder (BPD) have severe problems in social interactions that might be caused by deficits in social cognition. Since the findings about social-cognitive abilities in BPD are inhomogeneous, ranging from deficits to superior abilities, we aimed to investigate the neuronal basis of social cognition in BPD. We applied a paradigm with three social cognition tasks, differing in their complexity: basal processing of faces with a neutral expression, recognition of emotions, and attribution of emotional intentions (affective ToM). A total of 13 patients with BPD and 13 healthy matched controls (HCs) were included in a functional magnet resonance imaging study. BPD patients showed no deficits in social cognition on the behavioral level. However, while HCs showed increasing activation in areas of the mirror neuron system with increasing complexity in the social-cognitive task, BPD patients had hypoactivation in these areas and hyperactivation in the amygdala which were not modulated by task complexity. This activation pattern seems to reflect an enhanced emotional approach in the processing of social stimuli in BPD that allows good performance in standardized social-cognitive tasks, but might be the basis of social-cognitive deficits in real-life social interactions.

Acetylcholine esterase inhibitor donepezil improves dynamic cerebrovascular regulation in Alzheimer patients.

AbstractBackgroundAlzheimers disease (AD) leads to a degeneration of the nucleus basalis of Meynert and thus to decreased cholinergic tonus in the brain. The transcription of endothelial nitric oxide synthase depends on an adequate cholinergic innervation of microvessels and vasoregulative abnormalities have been reported in AD. We investigated activationflow coupling to study the role of acetylcholine esterase inhibition (AChEI) on vasoregulative function.MethodsA functional transcranial Doppler approach was used to measure the visually evoked flow velocity response in the posterior cerebral artery in AD patients who had no vascular risk factors. The diagnosis of AD was made according to the ICD10/DSMIIIR–criteria. After baseline recording the effect of four weeks 5mg donepezil and then four weeks 10 mg was investigated. Doppler data were evaluated with a control system approach to obtain dynamic properties of vasoregulation and were compared with a healthy control group.ResultsAD patients showed an increased damping (0.64 ± 0.2; p = 0.007 vs. control) in evoked responses and lower resting flow velocity levels (40 ± 13 cm/s; p = 0.06 vs. control), which were restored in a dose–dependent manner under AChEI (0.4 ± 0.2; 44 ± 11 cm/s).ConclusionsAD is associated with a functional vasoregulative deficit possibly due to decreased levels of the endothelial nitric oxide synthase. Augmenting levels with AChEI normalized flow regulation possibly leading to a better blood supply to active neurons.

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.

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

Lis S, Baer N, Stein‐en‐Nosse C, Gallhofer B, Sammer G, Kirsch P. Objective measurement of motor activity during cognitive performance in adults with attention‐deficit/hyperactivity disorder.

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.

The involvement of emotion recognition in affective theory of mind

This study was conducted to explore the relationship between emotion recognition and affective Theory of Mind (ToM). Forty subjects performed a facial emotion recognition and an emotional intention recognition task (affective ToM) in an event-related fMRI study. Conjunction analysis revealed overlapping activation during both tasks. Activation in some of these conjunctly activated regions was even stronger during affective ToM than during emotion recognition, namely in the inferior frontal gyrus, the superior temporal sulcus, the temporal pole, and the amygdala. In contrast to previous studies investigating ToM, we found no activation in the anterior cingulate, commonly assumed as the key region for ToM. The results point to a close relationship of emotion recognition and affective ToM and can be interpreted as evidence for the assumption that at least basal forms of ToM occur by an embodied, non-cognitive process.