Birgit Völlm

Neuronal correlates of theory of mind and empathy: A functional magnetic resonance imaging study in a nonverbal task

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.

Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials

BACKGROUND Many patients with borderline personality disorder receive pharmacological treatment, but there is uncertainty about the usefulness of such therapies. AIMS To evaluate the evidence of effectiveness of pharmacotherapy in treating different facets of the psychopathology of borderline personality disorder. METHOD A Cochrane Collaboration systematic review and meta-analysis of randomised comparisons of drug v. placebo, drug v. drug, or single drug v. combined drug treatment in adult patients with borderline personality disorder was conducted. Primary outcomes were overall disorder severity as well as specific core symptoms. Secondary outcomes comprised associated psychiatric pathology and drug tolerability. RESULTS Twenty-seven trials were included in which first- and second-generation antipsychotics, mood stabilisers, antidepressants and omega-3 fatty acids were tested. Most beneficial effects were found for the mood stabilisers topiramate, lamotrigine and valproate semisodium, and the second-generation antipsychotics aripiprazole and olanzapine. However, the robustness of findings is low, since they are based mostly on single, small studies. Selective serotonin reuptake inhibitors so far lack high-level evidence of effectiveness. CONCLUSIONS The current evidence from randomised controlled trials suggests that drug treatment, especially with mood stabilisers and second-generation antipsychotics, may be effective for treating a number of core symptoms and associated psychopathology, but the evidence does not currently support effectiveness for overall severity of borderline personality disorder. Pharmacotherapy should therefore be targeted at specific symptoms.

The QCAE: A Questionnaire of Cognitive and Affective Empathy

Empathy has been inconsistently defined and inadequately measured. This research aimed to produce a new and rigorously developed questionnaire. Exploratory (n 1= 640) and confirmatory (n 2= 318) factor analyses were employed to develop the Questionnaire of Cognitive and Affective Empathy (QCAE). Principal components analysis revealed 5 factors (31 items). Confirmatory factor analysis confirmed this structure in an independent sample. The hypothesized 2-factor structure (cognitive and affective empathy) was tested and provided the best and most parsimonious fit to the data. Gender differences, convergent validity, and construct validity were examined. The QCAE is a valid tool for assessing cognitive and affective empathy.

Serotonergic Modulation of Neuronal Responses to Behavioural Inhibition and Reinforcing Stimuli: An fMRI Study in Healthy Volunteers

Serotonin (5‐HT) has been implicated in the aetiology of a number of psychiatric conditions, including depression, anxiety and antisocial personality disorder. The development of these disorders may arise from alterations in underlying motivational and cognitive processes such as emotional recognition, reinforcement processing and central inhibitory control. This study aimed to localize where in the brain 5‐HT modulates neuropsychological processes relevant to putative 5‐HT disorders, using functional magnetic resonance imaging. We examined the effect of the antidepressant mirtazapine on brain activations associated with behavioural inhibition and reinforcement processing in healthy subjects. Forty‐five men were randomly allocated to receiving mirtazapine or placebo in a double‐blind fashion. A Go/No‐Go, Reward/No‐Reward and Loss/No‐loss task were performed during functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner. Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task activations were largely consistent with previous findings. Mirtazapine modulated brain activations in the Go/No‐Go and Reward/No‐Reward task. During behavioural inhibition, enhanced activations were observed in the right orbitofrontal cortex (BA47). Increased activations in bilateral parietal cortex were found during the Reward task while no significant interaction was observed in the Loss task. Our results support the suggestion of an important role of serotonin in modulating basic processes involved in psychiatric disorders. Combining drug challenge with fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in healthy as well as patient groups.

Antisocial personality disorder and psychopathy in women: a literature review on the reliability and validity of assessment instruments.

Crime rates are low in women compared to men. The two disorders most commonly associated with offending behaviour, antisocial personality disorder (ASPD) and psychopathy, are also less prevalent in female samples. However, developments in forensic psychiatry have often ignored gender, and the utility of constructs such as psychopathy and their assessment instruments in female samples remains unclear. This article presents a review of studies looking at rates of ASPD and psychopathy and on the reliability and validity of assessment instruments of these disorders in women. Gender differences in symptom patterns will be considered. The literature seems to suggest that DSM-IV criteria for ASPD may lead to an underestimation of the prevalence of the disorder in women due to the requirement of childhood conduct disorder symptoms. The Psychopathy Checklist-Revised (PCL-R) is a valid and reliable instrument to identify psychopathy in women but there are gender differences in the factor structure and item loadings on this measure. Research to date seems to suggest a three-factor model may be most strongly supported in females. Preliminary evidence suggests the PCL-R may have some value in predicting future offending while the PCL:SV may be useful in predicting institutional violence. Clinical implications are discussed.

Neuronal correlates of reward and loss in Cluster B personality disorders: A functional magnetic resonance imaging study

Decision making is guided by the likely consequences of behavioural choices. Neuronal correlates of financial reward have been described in a number of functional imaging studies in humans. Areas implicated in reward include ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Response to loss has not been as extensively studied but may involve prefrontal and medial temporal cortices. It has been proposed that increased sensitivity to reward and reduced sensitivity to punishment underlie some of the psychopathology in impulsive personality disordered individuals. However, few imaging studies using reinforcement tasks have been conducted in this group. In this fMRI study, we investigate the effects of positive (monetary reward) and negative (monetary loss) outcomes on BOLD responses in two target selection tasks. The experimental group comprised eight people with Cluster B (antisocial and borderline) personality disorder, whilst the control group contained fourteen healthy participants. A key finding was the absence of prefrontal responses and reduced BOLD signal in the subcortical reward system in the PD group during positive reinforcement. Impulsivity scores correlated negatively with prefrontal responses in the PD but not the control group during both, reward and loss. Our results suggest dysfunctional responses to rewarding and aversive stimuli in Cluster B personality disordered individuals but do not support the notion of hypersensitivity to reward and hyposensitivity to loss.

Moral decision-making, ToM, empathy and the default mode network

Automatic intuitions and deliberate reasoning, sourcing internal representations of our personal norms and values, contribute to our beliefs of what is right and wrong. We used fMRI to directly compare moral (M) and non-moral (NM) decision-making processes using scenarios requiring conscious deliberation, whereby the main character declared an intention to take a course of action. Furthermore, we examined the relationship between BOLD signal, associated with M>NM decision-making, and moral judgment competence, psychopathy, and empathy. We observed greater activity in various parts of Theory of Mind, empathy and default mode networks during M>NM decision-making. There was a trend for high scores on primary psychopathy to correlate with decreased M>NM BOLD activation in an area extending from dorsolateral prefrontal cortex to medial prefrontal cortex. We suggest that moral decision-making entails a greater degree of internally directed processing, such as self-referential mental processing and the representation of intentions and feelings, than non-moral decision-making.

Neuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals

Individuals with antisocial personality disorder (ASPD) are impulsive and show impairment in reinforcement processing. There is increasing evidence for a neurobiological basis of psychopathy, which shares some of the characteristics of ASPD, but research on the neuronal correlates of neuropsychological processes in ASPD remains limited. Furthermore, no research has examined the effects of serotonergic manipulation on brain activations in antisocial groups. In this study, 25 male participants with ASPD (mean age 42.1) and 32 male control participants (mean age 30.5; 25 participants providing usable scans) were randomly allocated to receive the 5-HT(2C)-agonist mCPP or placebo. Participants were scanned using functional magnetic resonance imaging (fMRI) during a behavioural inhibition (Go/NoGo) and a reward task. In comparison to healthy controls the ASPD group showed reduced task related activations in the dorsolateral prefrontal cortex (DLPFC) but increased signal in the pre/subgenual anterior cingulate cortex (ACC) in the Go/No-Go task and increased activation in OFC in the reward task. mCPP modulated brain responses in both tasks in the whole group. Interactions between group and drug occured in bilateral OFC, caudate and ventral pallidum during the reward task but no significant interactions were found in the Go/No-Go task. This suggests that ASPD involves altered serotonin modulation of reward, but not motor inhibition pathways. These findings suggest that ASPD involves altered DLPFC, ACC and OFC function. Altered serotonergic modulation of reward pathways seen in the ASPD group raises the possibility that targeting serotonin systems may be therapeutic.

Co-operation with another player in a financially rewarded guessing game activates regions implicated in theory of mind.

Abstract Functional imaging studies have identified a network of brain regions associated with theory of mind (ToM); the attribution of mental states to other people. Similar regions have also been observed in studies where people play games that involve either competing or co-operating with another person. Such games are thought to place implicit demands on ToM processes. Co-operation with others has also been shown to elicit brain responses in areas associated with the processing of reward, suggesting that co-operation is an intrinsically rewarding process. In this study, we used a factorial design to assess the interaction between co-operation and the availability of financial rewards in a guessing game. Twelve subjects were scanned with functional magnetic resonance imaging (fMRI) while they performed a guessing game with and without co-operation, and under both these conditions with and without financial reward. The main effect of co-operation was associated with neural responses in theory of mind regions, while the main effect of financial reward was associated with neural responses in reward regions. Critically the response to reward in medial orbitofrontal cortex was significantly enhanced when subjects were co-operating. This suggests that rewards achieved through co-operation are more valuable than rewards achieved alone.

A voxel-based morphometric MRI study in men with borderline personality disorder: preliminary findings

OBJECTIVE There is increasing evidence for subtle changes in brain morphology and function in patients with borderline personality disorder (BPD). Structural brain imaging studies show lower volume in frontal, temporal and parietal brain regions than in healthy controls. The aim of our preliminary study of men with BPD was to investigate structural brain changes and their relationship with a measure of impulsivity. METHODS We examined seven male patients with BPD and six control men using voxel-based morphometry. Analysis of covariance was carried out to assess regionally specific differences in grey and white matter (WM) volumes. Correlations between trait impulsivity as measured using the Impulsiveness-Venturesomeness-Empathy scale and brain volumes were studied. RESULTS Compared with healthy men, men with BPD had similar WM volumes but smaller grey matter (GM) volumes in frontal, temporal and parietal cortices. The latter were negatively correlated with trait impulsivity. CONCLUSIONS Our findings fit with previous reports of smaller regional GM volumes reported in women with BPD, and suggest that in men there may be an association between smaller GM volumes and impulsivity.