Sylvia Terbeck

Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearmans ρs⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

Are You Morally Modified?: The Moral Effects of Widely Used Pharmaceuticals.

A number of concerns have been raised about the possible future use of pharmaceuticals designed to enhance cognitive, affective, and motivational processes, particularly where the aim is to produce morally better decisions or behavior. In this article, we draw attention to what is arguably a more worrying possibility: that pharmaceuticals currently in widespread therapeutic use are already having unintended effects on these processes, and thus on moral decision making and morally significant behavior. We review current evidence on the moral effects of three widely used drugs or drug types: (i) propranolol, (ii) selective serotonin reuptake inhibitors, and (iii) drugs that effect oxytocin physiology. This evidence suggests that the alterations to moral decision making and behavior caused by these agents may have important and difficult-to-evaluate consequences, at least at the population level. We argue that the moral effects of these and other widely used pharmaceuticals warrant further empirical research and ethical analysis.

Virtual Morality: Transitioning from Moral Judgment to Moral Action?

The nature of moral action versus moral judgment has been extensively debated in numerous disciplines. We introduce Virtual Reality (VR) moral paradigms examining the action individuals take in a high emotionally arousing, direct action-focused, moral scenario. In two studies involving qualitatively different populations, we found a greater endorsement of utilitarian responses–killing one in order to save many others–when action was required in moral virtual dilemmas compared to their judgment counterparts. Heart rate in virtual moral dilemmas was significantly increased when compared to both judgment counterparts and control virtual tasks. Our research suggests that moral action may be viewed as an independent construct to moral judgment, with VR methods delivering new prospects for investigating and assessing moral behaviour.

Beta adrenergic blockade reduces utilitarian judgement.

Highlights ► We investigated the role of noradrenergic transmission in moral decision-making. ► The beta-adrenoceptor antagonist propranolol affected responses to moral dilemmas. ► Propranolol reduced the willingness to endorse utilitarian solutions involving harm. ► Propranolol also reduced heart rate and response times, and increased decisiveness. ► Blockade of noradrenergic arousal appears to increase aversion to harming others.

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches—from basic neurobiological approaches to human studies—might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5s important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoCs arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

Noradrenaline effects on social behaviour, intergroup relations, and moral decisions.

Recent research has begun to elucidate the neural basis of higher order social concepts, such as the mechanisms involved in intergroup relations, and moral judgments. Most theories have concentrated on higher order emotions, such as guilt, shame, or empathy, as core mechanisms. Accordingly, psychopharmacological and neurobiological studies have investigated the effects of manipulating serotonin or oxytocin activity on moral and social decisions and attitudes. However, recently it has been determined that changes in more basic emotions, such as fear and anger, might also have a significant role in social and moral cognition. This article summarizes psychopharmacological and fMRI research on the role of noradrenaline in higher order social cognition suggesting that indeed noradrenergic mediated affective changes might play key - and probably causal - role in certain social attitudes and moral judgments. Social judgments may also be directly influenced by numerous neurotransmitter manipulations but these effects could be mediated by modulation of basic emotions which appear to play an essential role in the formation of social concepts and moral behaviour.

The Neuroscience of Prejudice

In this chapter the neuroscience of prejudice will be discussed. Firstly, a basic introduction to brain anatomy will be given. Secondly, neuroscience research methods, in particular functional Magnetic Resonance Imaging (fMRI) will be explained. In addition psychopharmacology as a research method will be examined. Subsequently, social neuroscience research will be presented, specifically, neuroscience research that investigated intergroup relations. Multiple studies have determined that basic face processing also involves automatic detection of social features, such as age, race, and gender. Furthermore a network of limbic (part of the brain associated with emotion) as well as frontal cortex structures (areas of the brain associated with higher order integrating emotional experiences and processing executive functions) can be associated with processing of in-group and out-group stimuli. Psychopharmacology, amongst other methods, might deliver a novel methodological approach to determine the involvement of neurotransmitter functions in racial biases.

Effect of short-term escitalopram treatment on neural activation during emotional processing:

Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significant reduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have a distinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed to explore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing, and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day 7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantly reduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrus following escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed that escitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus and amygdala, an effect that seems to be distinguishable from that of other SSRIs.

Cognitive Psychological Support for the ADC Model of Moral Judgment

“It is important to provide a common theoretical framework that would link the neuroscience and cognitive science literature on decision making and moral judgment, and the ADC approach with the REACT model is a step in this direction” (Dubljevi c and Racine 2014, 15). Previously, cognitive psychologists researching rationality and decision making mostly utilized a dual-process framework (Evans 2008). However, recently this approach has been brought into question. Here we show how new theoretical frameworks in cognitive psychology can deliver support for the ADC model of moral intuitions proposed by Dubljevi c and Racine. The main goal of this commentary is thus to demonstrate that some tasks typically thought to involve reflective processes, such as evaluating the validity of a conclusion or incorporating base rates into posterior probability judgments, can also be accomplished intuitively. These findings from experimental cognitive psychology support key aspects of the ADC model. Dubljevi c and Racine proposed a three-component model of moral intuition. The authors stated that actions, deeds, and consequences (ADC) are elicited intuitively and subsequently processed/evaluated in order to arrive at a moral decision. The first two intuitions are suggested to be related to social dimensions—socially acceptable behaviors (D), and virtues of the agent (A)—while the third type of intuition is suggested to be related to the anticipated outcome (C). Previous research in moral psychology suggested that this aspect might have a strong reflective component (e.g., Greene et al. 2008). Greene (2009) suggested that deontological judgments have a stronger emotional/intuitive aspect, while reflection/ higher order cognitive processing was involved in utilitarian decisions. However, Dubljevi c and Racine criticized some experimental research, as it would not allow the full range of moral theory to be covered. Dubljevi c and Racine argued that the requirement of conscious analysis of consequences in order to act might be maladaptive: “Consequence tallying has to be very fast because in reallife situations, moral intuitions concerning saving lives involve split-second decisions in which ‘paralysis by overanalysis’ can be costly” (15). Dubljevi c and Racine present a theoretical rationale and philosophically based analysis for their proposal; here we present a brief overview of recent research in the cognitive psychology of reasoning that similarly suggests that judgments previously thought to depend upon reflective reasoning can instead be accomplished through intuitive processing.

A comparison of immersive virtual reality with traditional neuropsychological measures in the assessment of executive functions

Objective This study investigated immersive virtual reality (IVR), as a novel technique to test executive function of healthy younger and older adults. We predicted IVR tasks to have greater predictive power than traditional measures when assessing age-related cognitive functioning due to the real-world validity of the tasks. Methods Participants (n=40) completed the Stroop colour–word test and the trail-making test (TMT) as traditional and commonly used assessments of executive functioning. Participants then completed three IVR tasks; a seating arrangement task, an item location task (both set in a virtual chemistry lab), and a virtual parking simulator. Results Younger adults completed significantly more parking simulator levels (p<0.001), placed significantly more objects (p<0.001), and located significantly more items than older adults (p<0.01), demonstrating higher levels of performance. Significant correlations were found between performance on traditional neuropsychological measures and IVR measures. For example, Stroop CW performance significantly correlated with the number of parking simulator levels completed (τ=0.43, p<0.01). This suggests that IVR measures assess the same underlying cognitive constructs as traditional tasks. In addition, IVR measures contributed a significant percentage of the explained variance in age. Conclusion IVR measures (i.e. number of parking simulator levels completed and number of objects placed in the seating arrangement task) were found to be stronger contributors than existing traditional neuropsychological tasks in predicting age-related cognitive decline. Future research should investigate the implementation of these real-world-based tasks in clinical groups given this promising initial work.