P300 and delay-discounting in obsessive-compulsive disorder.

Previous research showed that dysfunctions of fronto-striatal neural networks are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Accordingly, patients with OCD showed altered performances during decision-making tasks. As P300, evoked by oddball paradigms, is suggested to be related to attentional and cognitive processes and generated in the medial temporal lobe and orbitofrontal and cingulate cortices, it is of special interest in OCD research. Therefore, this study aimed to investigate P300 in OCD and its associations with brain activity during decision-making: P300, evoked by an auditory oddball paradigm, was analysed in 19 OCD patients and 19 healthy controls regarding peak latency, amplitude and source density power in parietal cortex areas by sLORETA. Afterwards, using a fMRI paradigm, Blood-oxygen-level-dependent (BOLD) contrast imaging was conducted during a delay-discounting paradigm. We hypothesised differences between groups regarding P300 characteristics and associations with frontal activity during delay-discounting. The P300 did not differ between groups, however, the P300 latency over the P4 electrode correlated negatively with the NEO-FFI score openness to experience in patients with OCD. In healthy controls, P300 source density power correlated with activity in frontal regions when processing rewards, a finding which was absent in OCD patients. To conclude, associations of P300 with frontal brain activation during delay-discounting were found, suggesting a contribution of attentional or context updating processes. Since this association was absent in patients with OCD, the findings could be interpreted as being indeed related to dysfunctions of fronto-striatal neural networks in patients with OCD.

Pareidolias and Creativity in Patients with Mental Disorders.

OBJECTIVE: Pareidolias are ilusionary misjudgments and are seen as the result of deliberately or unconsciously caused misinterpretations by the human brain, which tends to complete diffuse and apparently incomplete perceptual images. The psychopathological value of pareidolia in the context of neuropsychiatric diseases has, however, been little researched so far. METHODS: In this pilot study, a total of 25 patients (mean age 43.3 years, SD 16.2) with an affective disorder or schizophrenic disease (ICD-10: F3.X or F2.X) and 25 healthy volunteers (mean age 46.1 years, SD 15.4) were compared for sociodemographic factors and psychometric findings, as well as pareidolias and creativity. RESULTS: We found that the patients identified significantly fewer pareidolias than healthy controls (p = 0.002) and that patients with schizophrenia, in particular, had a significantly lower hit rate (p = 0.005). Across the whole group, there were clear positive correlations between pareidolia and high creativity, as well as personality traits such as impulsiveness/spontaneity, extraversion, and conscientiousness. CONCLUSIONS: Unexpectedly, having less nosology-specific features than individual specific properties such as creativity and extraversion, and especially openness and verbal intelligence, in patients with affective disorder or schizophrenia promotes the recognition of pareidolia as a specific form of illusionary misperception.

Enhanced Processing of Painful Emotions in Patients With Borderline Personality Disorder: A Functional Magnetic Resonance Imaging Study.

Previous research has demonstrated that patients with borderline personality disorder (BPD) are more sensitive to negative emotions and often show poor cognitive empathy, yet preserved or even superior emotional empathy. However, little is known about the neural correlates of empathy. Here, we examined empathy for pain in 20 patients with BPD and 19 healthy controls (HC) in a functional magnetic resonance imaging (fMRI) study, which comprised an empathy for pain paradigm showing facial emotions prior to hands exposed to painful stimuli. We found a selectively enhanced activation of the right supramarginal gyrus for painful hand pictures following painful facial expressions in BPD patients, and lower activation to nonpainful pictures following angry expressions. Patients with BPD showed less activation in the left supramarginal gyrus when viewing angry facial expressions compared to HC, independent of the pain condition. Moreover, we found differential activation of the left anterior insula, depending on the preceding facial expression exclusively in patients. The findings suggest that empathy for pain becomes selectively enhanced, depending on the emotional context information in patients with BPD. Another preliminary finding was an attenuated response to emotions in patients receiving psychotropic medication compared to unmedicated patients. These effects need to be replicated in larger samples. Together, increased activation during the observation of painful facial expressions seems to reflect emotional hypersensitivity in BPD.

Childhood trauma affects processing of social interactions in borderline personality disorder: An event-related potential study investigating empathy for pain.

Objectives: Patients with borderline personality disorder (BPD) have difficulties in empathising with others and show disturbances in social interactions. Using a 'Social Interaction Empathy Task', we found that BPD patients judged neutral and psychologically painful conditions as more painful than healthy subjects. Here, we present the neural correlates underlying these differences in empathy for pain. Methods: Female BPD patients and healthy controls completed the 'Social Interaction Empathy Task' during EEG recording. Event-related potentials (ERP) were analysed for an early anterior component and a late latency positivity. Empathic abilities were assessed using the Interpersonal Reactivity Index and early aversive experiences were measured by the Childhood Trauma Questionnaire (CTQ). Results: ERPs in the patient group matched the behaviour results and correlated with the level of personal distress and CTQ. In addition, ERPs of patients were predicted by childhood maltreatment and stress. Conclusions: Taken together, our findings indicate that the observed behavioural differences between patients with BPD and controls might be due to modulatory effects of empathic abilities on the evaluation of pain-related social stimuli, which are supposed to be based on childhood maltreatment.

Kinematic Analysis of Handwriting Movements in Individuals with Intellectual Disabilities with and without Obsessive Compulsive Symptoms.

Theory/calculation: Movement disorders such as disturbances of coordination, clumsiness, and hand-related stereotypies are a frequent phenomenon in individuals with intellectual disabilities (ID). Obsessive-compulsive symptoms are also common in persons with ID. Our aim was to investigate hand motor dysfunction in persons with ID with and without OCD, using a digitizing tablet and the kinematic analysis of handwriting and drawing movements. METHODS: We examinedthe hand motor performance of 23 individuals (12 males, 11 females, 42.6 ± 13.7 years old) with ID of heterogeneous aetiology. All subjects were required to write a sentence and draw circles under various conditions. Kinematic parameters were calculated to quantify hand motion. RESULTS: Individuals with ID exhibit serious hand motor impairments suggestive of bradykinesia, irregularity, and micrographia. More than half of our ID patients (60.9%) displayed obsessive-compulsive symptoms of moderate severity (Y-BOCS total score: 16.6 ± 8.3). Interestingly, the ID patients with OCD displayed smaller amplitudes of hand motor movements than did patients with no obsessive-compulsive symptoms, while differences observed in the writing and drawing concentric circles trials were significant. CONCLUSIONS: The results of this pilot study support the use of kinematic analyses of handwriting movements to evaluate motor abnormalities in patients with ID and comorbid mental illnesses.

Relationship Between Neuroanatomical and Serotonergic Hypotheses of Obsessive-Compulsive Disorder: A Combined Functional Magnetic Resonance Imaging-Evoked Potential Study.

OBJECTIVE: The so-called neuroanatomical hypothesis (with an increased activity of orbitofrontal cortex [OFC]) and the serotonergic hypothesis (with low activity in this system) have been discussed regarding the pathogenesis of obsessive-compulsive disorder (OCD) for decades. This study aimed to look for a relationship between the 2 pathogenetic concepts. METHODS: Nineteen OCD patients (8 female, 11 male, mean ± SD age = 33.37 ± 11.73 years, Yale-Brown Obsessive Compulsive Scale: 21.79 ± 6.59; diagnosed by ICD-10/DSM-IV-TR) were compared to 19 matched healthy controls (8 female, 11 male, mean ± SD age = 31.63 ± 10.79 years) and investigated (2012-2014) with the loudness dependence of auditory-evoked potentials (LDAEP) as a marker of the synaptic serotonergic activity and functional magnetic resonance imaging (fMRI) during the delay discounting paradigm, inducing OFC blood-oxygen level-dependent activity in the 2 groups. RESULTS: There were significant correlation coefficients between LDAEP (eLORETA right side) and fMRI OFC activities (anatomic region of interest) within the delay discounting paradigm (immediate vs control) in patients with OCD (r = -0.554; P = .014). LDAEP differed between the 2 groups with larger LDAEP at Cz in OCD patients indicating low serotonergic activity (0.28 ± 0.14 vs 0.20 ± 0.10 µV/10 dB, F2,35 = 4.66, P = .016). fMRI activations of dorsolateral and medial prefrontal cortex as well as ventral striatum (functional region of interest) were different between OCD and healthy volunteers. CONCLUSIONS: The 2 main pathophysiologic hypotheses of OCD seem to be related to each other as measured by LDAEP and fMRI OFC activity during the delay discounting task. This could be interpreted as a further hint that low serotonergic activity induces altered OFC responsivity, which has to be treated in each patient with OCD by a serotonin agonist.

Forgiveness and cognitive control - Provoking revenge via theta-burst-stimulation of the DLPFC.

In order to act in a socially acceptable way, the ability to forgive is indispensable. It has been suggested that forgiveness relies on cognitive control, more specifically inhibition. In this study, we combined an ultimatum game (UG) and a dictator game (DG) with inhibitory, continuous theta-burst stimulation (cTBS; verum vs. placebo, within-subjects design) of the right dorsolateral prefrontal cortex (DLPFC) to investigate the effect of reduced cognitive control on forgiveness. To this end, participants played an UG against fair and unfair opponents, where they had to accept or reject (fair and unfair) monetary offers, and then received a cTBS prior to playing a DG against the same opponents with reversed roles. The participants now had the possibility to forgive the unfair opponents (allocation of a fair amount of money) or to take revenge whereby the cTBS effects were assessed with functional near-infrared spectroscopy. Following verum cTBS, participants allocated significantly less money to their unfair opponents than in the placebo cTBS condition. Also, reaction times (RTs) differed significantly between verum and placebo cTBS for unfair opponents (higher RTs following verum stimulation) but not for fair opponents. These results strongly indicate that cognitive control is a fundamental requirement for overcoming unwanted emotional responses.

Retaliation or selfishness? An rTMS investigation of the role of the dorsolateral prefrontal cortex in prosocial motives.

Equity, fairness and cooperative behavior are crucial for everyday social interactions. Recent neuroimaging studies suggest that the dorsolateral prefrontal cortex (DLPFC) is involved in the evaluation of violations of fairness rules, though difficulties remain to determine its role in implementing retaliating or forgiving responses to unfairness. Accordingly, we applied repetitive transcranial magnetic stimulation (rTMS) to the left and right DLPFC and investigated the impact of the DLPFC on retaliation and selfishness using a sequential neuroeconomic task establishing a role reversal. That is, participants first played an Ultimatum Game (in the role of a recipient) against fair or unfair proposers, followed by a Dictator Game in the role of a proposer. Following inhibition of the right DLPFC, subjects showed an increased punishment rate regarding previously unfair opponents. Surprisingly, previously fair opponents were also treated less fairly after rTMS to the right DLPFC, but not after left or sham rTMS. Previous work suggests that the right DLPFC provides "top-down" cognitive control over prepotent emotional responses to unfairness. Our results indicate, however, that the right DLPFC may be involved in controlling selfish behavior and that its suppression leads to maximization of one's own benefit, regardless of another's fairness or unfairness in previous encounters.

Altered Empathy for Psychological and Physical Pain in Borderline Personality Disorder.

Many patients with borderline personality disorder (BPD) experience difficulties in empathizing with others and are sensitive to social exclusion. Accordingly, the authors developed a novel Social Interaction Empathy Task to examine empathy for physical and psychological pain from first- and third-person perspectives. Fifty female patients with BPD and forty-eight controls matched for age and gender were included. Alexithymia was also measured. Patients with BPD rated neutral and psychologically painful situations as more painful than healthy controls, and patients with BPD rated psychological pain as more intense in the first-person perspective than in the third-person perspective. In contrast, controls did not differentiate between the perspectives and rated physical pain as most intense. The impact of early adversity on empathy for psychological pain was mediated by alexithymia. Increased sensitivity for psychological pain in BPD correlated with symptom severity. BPD is associated with altered empathy for pain, which is related to difficulties in reflecting emotional states.

Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

BACKGROUND: The orbitofrontal cortex seems to play a crucial role in reward-guided learning and decision making, especially for impulsive choice procedures including delayed reward discounting. The central serotonergic system is closely involved in the regulation of impulsivity, but how the serotonergic firing rate and release, best investigated by the loudness dependence of auditory evoked potentials (LDAEP), interact with orbitofrontal activity is still unknown. METHODS: Twenty healthy volunteers (11 males, 9 females, 31.3 ± 10.6 years old) were studied in a 3T MRI scanner (Philips, Hamburg, Germany) during a delay discounting task, after their LDAEP was recorded using a 32 electrodes EEG machine (Brain Products, Munich, Germany). RESULTS: Significant positive correlations were only found between the LDAEP and the medial orbitofrontal part of the superior frontal gyrus (SFG/MO) [Δ immediate reward - delayed reward] for the right (r = 0.519; P = 0.019) and left side (r = 0.478; P = 0.033). This relationship was stronger for females compared with males. Orbitofrontal activity was also related to the Barratt Impulsivity Scale. CONCLUSIONS: This study revealed that low serotonergic activity as measured by a strong LDAEP was related to a high fMRI signal intensity of SFG/MO during immediate reward behavior which is related to impulsivity. Since this relationship was only found for the infralimbic medial and not for the middle or lateral part of the orbitofrontal cortex, an exclusive projection tract of the serotonergic system to this cortical region can be assumed to regulate impulsive reward-orientated decision making. Hum Brain Mapp 38:1507-1517, 2017. © 2016 Wiley Periodicals, Inc.

Empathy for pain-related dorsolateral prefrontal activity is modulated by angry face perception.

Empathy, i.e., the ability to perceive and share another person's affective state, is associated with activity in a complex neural network, including the anterior insula, the anterior and mid-cingulate cortex, and the lateral prefrontal cortex. Here, we were interested in the question how facial emotions influence the activation of the 'pain network'. In the present study, we used functional magnetic resonance imaging to investigate the neuronal correlates of empathy for pain and its interaction with emotional face recognition in 20 healthy subjects. We identified various brain regions commonly associated with empathy for pain, including the right mid-cingulate cortex, the left anterior insula (AI), and the left dorsolateral prefrontal cortex (dlPFC), with an increased neuronal response in the left dlPFC after the presentation of angry faces. Furthermore, a negative correlation between psychological measures of alexithymia and empathy for pain-related brain activity was observed in the left AI. The dlPFC is an important brain region involved in cognitive reappraisal or in 'top-down' control of the limbic system. Our findings could therefore reflect a regulatory response associated with distancing from negatively valenced stimuli. Moreover, our results underline the involvement of the AI in empathy for pain responses and their relationship to alexithymia.

Alterations of monetary reward and punishment processing in chronic cannabis users: an FMRI study.

Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (n = 15) and in healthy control subjects (n = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were - in contrast to healthy controls - not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.

"An eye for an eye"? Neural correlates of retribution and forgiveness.

Humans have evolved strong preferences for equity and fairness. Neuroimaging studies suggest that punishing unfairness is associated with the activation of a neural network comprising the anterior cingulate cortex, anterior insula, the ventral striatum, and the dorsolateral prefrontal cortex (DLPFC). Here, we report the neuronal correlates of retribution and "forgiveness" in a scenario, in which individuals first acted as a recipient in an Ultimatum Game, and subsequently assumed the position of a proposer in a Dictator Game played against the same opponents as in the Ultimatum Game. Most subjects responded in a tit-for-tat fashion, which was accompanied by activation of the ventral striatum, corroborating previous findings that punishing unfair behaviour has a rewarding connotation. Subjects distinguished between the human opponent and computer condition by activation of the ventromedial PFC in the human condition, indicative of mentalising. A substantial number of subjects did not retaliate. Neurally, this "forgiveness" behaviour was associated with the activation of the right (and to a lesser degree left) DLPFC, a region that serves as a cognitive control region and thus may be involved in inhibiting emotional responses against unfairness.

Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy.

Somatoform disorder patients show a variety of emotional disturbances including impaired emotion recognition and increased empathic distress. In a previous paper, our group showed that several brain regions involved in emotional processing, such as the parahippocampal gyrus and other regions, were less activated in pre-treatment somatoform disorder patients (compared to healthy controls) during an empathy task. Since the parahippocampal gyrus is involved in emotional memory, its decreased activation might reflect the repression of emotional memories (which-according to psychoanalytical concepts-plays an important role in somatoform disorder). Psychodynamic psychotherapy aims at increasing the understanding of emotional conflicts as well as uncovering repressed emotions. We were interested, whether brain activity in the parahippocampal gyrus normalized after (inpatient) multimodal psychodynamic psychotherapy. Using fMRI, subjects were scanned while they shared the emotional states of presented facial stimuli expressing anger, disgust, joy, and a neutral expression; distorted stimuli with unrecognizable content served as control condition. 15 somatoform disorder patients were scanned twice, pre and post multimodal psychodynamic psychotherapy; in addition, 15 age-matched healthy control subjects were investigated. Effects of psychotherapy on hemodynamic responses were analyzed implementing two approaches: (1) an a priori region of interest approach and (2) a voxelwise whole brain analysis. Both analyses revealed increased hemodynamic responses in the left and right parahippocampal gyrus (and other regions) after multimodal psychotherapy in the contrast "empathy with anger"-"control." Our results are in line with psychoanalytical concepts about somatoform disorder. They suggest the parahippocampal gyrus is crucially involved in the neurobiological mechanisms which underly the emotional deficits of somatoform disorder patients.

Differential reward processing in subtypes of adult attention deficit hyperactivity disorder.

OBJECTIVES: Abnormalities in reward processing have been found in adolescents and adults with ADHD using the 'Monetary Incentive Delay' (MID) task. However, ADHD groups in previous studies were heterogeneous regarding ADHD subtype, gender and, in part, drug treatment status. This study sought to compare neural activations in the ventral striatum (VS) and prefrontal regions during reward processing in homogenous ADHD subtype groups and healthy adults, using the MID task. METHODS: In total, 24 drug-naïve, right-handed male adults with ADHD (12 subjects with combined type (ADHD-ct) and 12 subjects with predominantly inattentive (ADHD-it) type ADHD), and twelve healthy right-handed male control subjects were included. RESULTS: Compared to ADHD-ct and healthy subjects, ADHD-it subjects showed a bilateral ventral striatal deficit during reward anticipation. In contrast, ADHD-ct subjects showed orbitofrontal hyporesponsiveness to reward feedback when compared with ADHD-it and healthy subjects. CONCLUSIONS: This is the first fMRI study that delineates dysfunctional and subtype-divergent neural and behavioural reward processing in adults with ADHD.

Personality functioning and the cortical midline structures--an exploratory FMRI study.

OBJECTIVE: Recent neuroscience studies explored the neuronal mechanisms underlying our sense of self. Thereby the cortical midline structures and their anterior and posterior regions have been shown to be central. What remains unclear though is how both, self and cortical midline structures, are related to the identity of the self which is of central importance in especially personality disorders. METHODS: Conducting an exploratory study with a dimensional approach, we here compared subjects with high and low level of personality functioning and identity integration as measured in a standardized way in fMRI during both, emotion- and reward-related tasks. RESULTS: Low levels of personality functioning and identity integration were predicted by significantly decreased degrees of deactivation in the anterior and posterior cortical midline structures. CONCLUSIONS: Though exploratory our results show for the first time direct relationship between cortical midline structures and personality functioning in terms of identity integration. This does not only contribute to our understanding of the neuronal mechanism underlying self and identity but carries also major implications for the treatment of patients with personality disorders.

Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.

Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.

Altered brain activity during emotional empathy in somatoform disorder.

Somatoform disorder patients suffer from impaired emotion recognition and other emotional deficits. Emotional empathy refers to the understanding and sharing of emotions of others in social contexts. It is likely that the emotional deficits of somatoform disorder patients are linked to disturbed empathic abilities; however, little is known so far about empathic deficits of somatoform patients and the underlying neural mechanisms. We used fMRI and an empathy paradigm to investigate 20 somatoform disorder patients and 20 healthy controls. The empathy paradigm contained facial pictures expressing anger, joy, disgust, and a neutral emotional state; a control condition contained unrecognizable stimuli. In addition, questionnaires testing for somatization, alexithymia, depression, empathy, and emotion recognition were applied. Behavioral results confirmed impaired emotion recognition in somatoform disorder and indicated a rather distinct pattern of empathic deficits of somatoform patients with specific difficulties in "empathic distress." In addition, somatoform patients revealed brain areas with diminished activity in the contrasts "all emotions"-"control," "anger"-"control," and "joy"-"control," whereas we did not find brain areas with altered activity in the contrasts "disgust"-"control" and "neutral"-"control." Significant clusters with less activity in somatoform patients included the bilateral parahippocampal gyrus, the left amygdala, the left postcentral gyrus, the left superior temporal gyrus, the left posterior insula, and the bilateral cerebellum. These findings indicate that disturbed emotional empathy of somatoform disorder patients is linked to impaired emotion recognition and abnormal activity of brain regions responsible for emotional evaluation, emotional memory, and emotion generation.

Involvement of glutamate in rest-stimulus interaction between perigenual and supragenual anterior cingulate cortex: a combined fMRI-MRS study.

The brain shows a high degree of activity at rest. The significance of this activity has come increasingly into focus. At present, however, the interaction between this activity and stimulus-induced activity is not well defined. The interaction between a task-negative (perigenual anterior cingulate cortex, pgACC) and task-positive (supragenual anterior cingulate cortex, sgACC) region during a simple task was thus investigated using a combination of fMRI and MRS. Negative BOLD responses in the pgACC were found to show a unidirectional effective connectivity with task-induced positive BOLD responses in the sgACC. This connectivity was shown to be related specifically with glutamate levels in the pgACC. These results demonstrate an interaction between deactivation from resting-state and resting-state glutamate levels in a task-negative region (pgACC), and task-induced activity in a task-positive region (sgACC). This provides insight into the neuronal and biochemical mechanisms by means of which the resting state activity of the brain potentially impacts upon subsequent stimulus-induced activity.