Decision Conflicts in Clinical Care during COVID-19: A Multi-Perspective Inquiry.

Background: The early COVID-19-pandemic was characterized by changes in decision making, decision-relevant value systems and the related perception of decisional uncertainties and conflicts resulting in decisional burden and stress. The vulnerability of clinical care professionals to these decisional dilemmas has not been characterized yet. Methods: A cross-sectional questionnaire study (540 patients, 322 physicians and 369 nurses in 11 institutions throughout Germany) was carried out. The inclusion criterion was active involvement in clinical treatment or decision making in oncology or psychiatry during the first year of COVID-19. The questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, and the perception of consequences for patients). Data analysis was performed using ANOVA, Pearson rank correlations, and the Chi²-test, and for inferential analysis, nominal logistic regression and tree classification were conducted. Results: Professionals reported changes in clinical management (27.5%) and a higher workload (29.2%), resulting in decisional uncertainty (19.2%) and decisional conflicts (22.7%), with significant differences between professional groups (p < 0.005), including anxiety, depression, loneliness and stress in professional subgroups (p < 0.001). Nominal regression analysis targeting "Decisional Uncertainty" provided a highly significant prediction model (LQ p < 0.001) containing eight variables, and the analysis for "Decisional Conflicts" included six items. The classification rates were 64.4% and 92.7%, respectively. Tree analysis confirmed three levels of determinants. Conclusions: Decisional uncertainty and conflicts during the COVID-19 pandemic were independent of the actual pandemic load. Vulnerable professional groups for the perception of a high number of decisional dilemmas were characterized by individual perception and the psychological framework. Coping and management strategies should target vulnerability, enable the handling of the individual perception of decisional dilemmas and ensure information availability and specific support for younger professionals.

Differences in Stakeholders' Perception of the Impact of COVID-19 on Clinical Care and Decision-Making.

Background: Pandemics are related to changes in clinical management. Factors that are associated with individual perceptions of related risks and decision-making processes focused on prevention and vaccination, but perceptions of other healthcare consequences are less investigated. Different perceptions of patients, nurses, and physicians on consequences regarding clinical management, decisional criteria, and burden were compared. Study Design: Cross-sectional OnCoVID questionnaire studies. Methods: Data that involved 1231 patients, physicians, and nurses from 11 German institutions that were actively involved in clinical treatment or decision-making in oncology or psychiatry were collected. Multivariate statistical approaches were used to analyze the stakeholder comparisons. Results: A total of 29.2% of professionals reported extensive changes in workload. Professionals in psychiatry returned severe impact of pandemic on all major aspects of their clinical care, but less changes were reported in oncology (p < 0.001). Both patient groups reported much lower recognition of treatment modifications and consequences for their own care. Decisional and pandemic burden was intensively attributed from professionals towards patients, but less in the opposite direction. Conclusions: All of the groups share concerns about the impact of the COVID-19 pandemic on healthcare management and clinical processes, but to very different extent. The perception of changes is dissociated in projection towards other stakeholders. Specific awareness should avoid the dissociated impact perception between patients and professionals potentially resulting in impaired shared decision-making.

Decision Conflicts in Clinical Care during COVID-19: A Patient Perspective.

(1) Background: Uncertainty is typical for a pandemic or similar healthcare crisis. This affects patients with resulting decisional conflicts and disturbed shared decision making during their treatment occurring to a very different extent. Sociodemographic factors and the individual perception of pandemic-related problems likely determine this decisional dilemma for patients and can characterize vulnerable groups with special susceptibility for decisional problems and related consequences. (2) Methods: Cross-sectional data from the OnCoVID questionnaire study were used involving 540 patients from 11 participating institutions covering all major regions in Germany. Participants were actively involved in clinical treatment in oncology or psychiatry during the COVID-19 pandemic. Questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, perception of consequences for patients) and very basic demographic data (age, gender, stage of treatment and educational background). Decision uncertainties and distress were operationalized using equidistant five-point scales. Data analysis was performed using descriptive and various multivariate approaches. (3) Results: A total of 11.5% of all patients described intensive uncertainty in their clinical decisions that was significantly correlated with anxiety, depression, loneliness and stress. Younger and female patients and those of higher educational status and treatment stage had the highest values for these stressors (p < 0.001). Only 15.3% of the patients (14.9% oncology, 16.2% psychiatry; p = 0.021) considered the additional risk of COVID-19 infections as very important for their disease-related decisions. Regression analysis identified determinants for patients at risk of a decisional dilemma, including information availability, educational level, age group and requirement of treatment decision making. (4) Conclusions: In patients, the COVID-19 pandemic induced specific decisional uncertainty and distress accompanied by intensified stress and psychological disturbances. Determinants of specific vulnerability were related to female sex, younger age, education level, disease stages and perception of pandemic-related treatment modifications, whereas availability of sufficient pandemic-related information prevented these problems. The most important decisional criteria for patients under these conditions were expected side effects/complications and treatment responses.

Changes and Challenges in Inpatient Mental Health Care During the First Two High Incidence Phases of the COVID-19 Pandemic in Germany - Results From the COVID Ψ Psychiatry Survey.

Psychiatric inpatient treatment, an important pillar of mental health care, is often of longer duration in Germany than in other countries. The COVID-19 pandemic called for infection prevention and control measures and thereby led to shifts in demand and inpatient capacities. The Germany-wide COVID Ψ Psychiatry Survey surveyed department heads of German psychiatric inpatient institutions. It assessed changes in utilization during the first two high incidence phases of the pandemic (spring 2020 and winter 2020/21) and also consequences for care, telemedicine experiences, hygiene measures, treatment of patients with mental illness and co-occuring SARS-CoV-2, and coercive measures in such patients. A total of n = 71 psychiatric departments (of 346 contacted) participated in the survey. The results showed a median decrease of inpatient treatment to 80% of 2019 levels and of day hospital treatment to 50% (first phase) and 70% (second phase). Reductions were mainly due to decreases in elective admissions, and emergency admissions remained unchanged or increased in 87% of departments. Utilization was reduced for affective, anxiety, personality, and addiction disorders but appeared roughly unaffected for psychotic disorders. A lack of integration of patients into their living environment, disease exacerbations, loss of contact, and suicide attempts were reported as problems resulting from reduced capacities and insufficient outpatient treatment alternatives. Almost all departments (96%) treated patients with severe mental illness and co-occurring SARS-CoV-2 infection. The majority established special wards and separate areas for (potentially) infectious patients. Telephone and video consultations were found to provide benefits in affective and anxiety disorders. Involuntary admissions of persons without mental illness because of infection protection law violations were reported by 6% of the hospitals. The survey showed high adaptability of psychiatric departments, which managed large capacity shifts and introduced new services for infectious patients, which include telemedicine services. However, the pandemic exacerbated some of the shortcomings of the German mental health system: Avoidable complications resulted from the lack of cooperation and integrated care sequences between in- and outpatient sectors and limited options for psychiatric hospitals to provide outpatient services. Preventive approaches to handle comparable pandemic situations in the future should focus on addressing these shortcomings.

No effect of a dopaminergic modulation fMRI task by amisulpride and L-DOPA on reward anticipation in healthy volunteers.

RATIONALE: Dysregulation of dopaminergic neurotransmission, specifically altered reward processing assessed via the reward anticipation in the MID task, plays a central role in the etiopathogenesis of neuropsychiatric disorders. OBJECTIVES: We hypothesized to find a difference in the activity level of the reward system (measured by the proxy reward anticipation) under drug administration versus placebo, in that amisulpride reduces, and L-DOPA enhances, its activity. METHODS: We studied the influence of dopamine agonist L-DOPA and the antagonist amisulpride on the reward system using functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task in n = 45 healthy volunteers in a randomized, blinded, cross-over study. RESULTS: The MID paradigm elicits strong activation in reward-dependent structures (such as ventral striatum, putamen, caudate, anterior insula) during reward anticipation. The placebo effect demonstrated the expected significant blood oxygen level-dependent activity in reward-dependent brain regions. Neither amisulpride nor L-DOPA led to significant changes in comparison with the placebo condition. This was true for whole-brain analysis as well as analysis of a pre-defined nucleus accumbens region-of-interest mask. CONCLUSION: The present results cast doubt on the sensitivity of reward anticipation contrast in the MID task for assessing dopamine-specific changes in healthy volunteers by pharmaco-fMRI. While our task was not well-suited for detailed analysis of the outcome phase, we provide reasonable arguments that the lack of effect in the anticipation phase is not due to an inefficient task but points to unexpected behavior of the reward system during pharmacological challenge. Group differences of reward anticipation should therefore not be seen as simple representatives of dopaminergic states.

Amisulpride and l-DOPA modulate subcortical brain nuclei connectivity in resting-state pharmacologic magnetic resonance imaging.

The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco-fMRI study using a double-blind, placebo-controlled design, where we examined the effect of l -DOPA, a dopamine precursor, and amisulpride, a D2/D3-receptor antagonist on resting-state FC in 45 healthy young adults using a cross-over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l -DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self-rated impulsivity goes together with a significant increase in VTA-mid-cingulate gyrus FC during l -DOPA-challenge. Therefore, our DA challenge modulated distinct large-scale subcortical connectivity networks. A dopamine-boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA-cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.

Interoception in insula subregions as a possible state marker for depression-an exploratory fMRI study investigating healthy, depressed and remitted participants.

BACKGROUND: Interoceptive awareness (iA), the awareness of stimuli originating inside the body, plays an important role in human emotions and psychopathology. The insula is particularly involved in neural processes underlying iA. However, iA-related neural activity in the insula during the acute state of major depressive disorder (MDD) and in remission from depression has not been explored. METHODS: A well-established fMRI paradigm for studying (iA; heartbeat counting) and exteroceptive awareness (eA; tone counting) was used. Study participants formed three independent groups: patients suffering from MDD, patients in remission from MDD or healthy controls. Task-induced neural activity in three functional subdivisions of the insula was compared between these groups. RESULTS: Depressed participants showed neural hypo-responses during iA in anterior insula regions, as compared to both healthy and remitted participants. The right dorsal anterior insula showed the strongest response to iA across all participant groups. In depressed participants there was no differentiation between different stimuli types in this region (i.e., between iA, eA and noTask). Healthy and remitted participants in contrast showed clear activity differences. CONCLUSIONS: This is the first study comparing iA and eA-related activity in the insula in depressed participants to that in healthy and remitted individuals. The preliminary results suggest that these groups differ in there being hypo-responses across insula regions in the depressed participants, whilst non-psychiatric participants and patients in remission from MDD show the same neural activity during iA in insula subregions implying a possible state marker for MDD. The lack of activity differences between different stimulus types in the depressed group may account for their symptoms of altered external and internal focus.

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.

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.

Culture modulates brain activity during empathy with anger.

Interdependent cultures (such as the Chinese) and independent cultures (such as the German) differ in their attitude towards harmony that is more valued in interdependent cultures. Interdependent and independent cultures also differ in their appreciation of anger--an emotion that implies the disruption of harmony. The present study investigated if interdependent and independent cultures foster distinct brain activity associated with empathic processing of familiar angry, familiar neutral, and unfamiliar neutral faces. Using functional MRI, we scanned Chinese and German healthy subjects during an intentional empathy task, a control task (the evaluation of skin color), and a baseline condition. The subject groups were matched with regard to age, gender, and education. Behaviorally, Chinese subjects described themselves as significantly more interdependent compared to German subjects. The contrast 'intentional empathy for familiar angry'>'baseline' revealed several regions, including the left inferior frontal cortex, the left supplementary motor area, and the left insula, that showed comparable hemodynamic responses in both groups. However, the left dorsolateral prefrontal cortex had stronger hemodynamic responses in Chinese subjects in the contrast 'intentional empathy for familiar angry'>'baseline'. Germans, in contrast, showed stronger hemodynamic responses in the right temporo-parietal junction, right inferior and superior temporal gyrus, and left middle insula for the same contrast. Hemodynamic responses in the latter three brain regions correlated with interdependences scores over all subjects. Our results suggest that enhanced emotion regulation during empathy with anger in the interdependent lifestyle is mediated by the left dorsolateral prefrontal cortex. Increased tolerance towards the expression of anger in the independent lifestyle, in contrast, is associated with increased activity of the right inferior and superior temporal gyrus and the left middle insula.

Neural substrates underlying intentional empathy.

Although empathic responses to stimuli with emotional contents may occur automatically, humans are capable to intentionally empathize with other individuals. Intentional empathy for others is even possible when they do not show emotional expressions. However, little is known about the neuronal mechanisms of this intentionally controlled empathic process. To investigate the neuronal substrates underlying intentional empathy, we scanned 20 healthy Chinese subjects, using fMRI, when they tried to feel inside the emotional states of neutral or angry faces of familiar (Asian) and unfamiliar (Caucasian) models. Skin color evaluation of the same stimuli served as a control task. Compared to a baseline condition, the empathy task revealed a network of established empathy regions, including the anterior cingulate cortex, bilateral inferior frontal cortex and bilateral anterior insula. The contrast of intentional empathy vs skin color evaluation, however, revealed three regions: the bilateral inferior frontal cortex, whose hemodynamic responses were independent of perceived emotion and familiarity and the right-middle temporal gyrus, whose activity was modulated by emotion but not by familiarity. These findings extend our understanding of the role of the inferior frontal cortex and the middle temporal gyrus in empathy by demonstrating their involvement in intentional empathy.

Are emotions associated with activity during rest or interoception? An exploratory fMRI study in healthy subjects.

Imaging studies investigating the default-mode network (DMN) of the brain revealed the phenomenon of elevated neural responses during periods of rest. This effect has been shown to be abnormally elevated in regions of the DMN concerning mood disorders like major depressive disorder (MDD). Since these disorders are accompanied by impaired emotional functioning, this leads to the suggestion of an association between activity during rest conditions and emotions, which remains to be demonstrated in a healthy and clinical population. Controlling for interoceptive processing, a process often closely connected to emotional functioning, we here demonstrate in an fMRI study of 30 healthy subjects the connection between activity during rest conditions in regions of the DMN and emotions in a psychologically, regionally, and stimulus specific way. Our findings provide further insight into the psychological functions underlying rest activity. Our findings in healthy subjects may also have future implications for a better understanding of mood disorders.

Multimodal psychodynamic psychotherapy induces normalization of reward related activity in somatoform disorder.

OBJECTIVES: Somatoform disorder patients demonstrate a disturbance in the balance between internal and external information processing, with a decreased focus on external stimulus processing. We investigated brain activity of somatoform disorder patients, during the processing of rewarding external events, paying particular attention to the effects of inpatient multimodal psychodynamic psychotherapy. METHODS: Using fMRI, we applied a reward task that required fast reactions to a target stimulus in order to obtain monetary rewards; a control condition contained responses without the opportunity to gain rewards. Twenty acute somatoform disorder patients were compared with twenty age-matched healthy controls. In addition, 15 patients underwent a second scanning session after participation in multimodal psychodynamic psychotherapy. RESULTS: Acute patients showed diminished hemodynamic differentiation between rewarding and non rewarding events in four regions, including the left postcentral gyrus and the right ventroposterior thalamus. After multimodal psychodynamic psychotherapy, both regions showed a significant normalization of neuronal differentiation. CONCLUSION: Our results suggest that diminished responsiveness of brain regions involved in the processing of external stimuli underlies the disturbed balance of internal and external processing of somatoform disorder patients. By providing new approaches to cope with distressing events, multimodal psychodynamic psychotherapy led to decreased symptoms and normalization of neuronal activity.

Is there a core neural network in empathy? An fMRI based quantitative meta-analysis.

Whilst recent neuroimaging studies have identified a series of different brain regions as being involved in empathy, it remains unclear concerning the activation consistence of these brain regions and their specific functional roles. Using MKDA, a whole-brain based quantitative meta-analysis of recent fMRI studies of empathy was performed. This analysis identified the dACC-aMCC-SMA and bilateral anterior insula as being consistently activated in empathy. Hypothesizing that what are here termed affective-perceptual and cognitive-evaluative forms of empathy might be characterized by different activity patterns, the neural activations in these forms of empathy were compared. The dorsal aMCC was demonstrated to be recruited more frequently in the cognitive-evaluative form of empathy, whilst the right anterior insula was found to be involved in the affective-perceptual form of empathy only. The left anterior insula was active in both forms of empathy. It was concluded that the dACC-aMCC-SMA and bilateral insula can be considered as forming a core network in empathy, and that cognitive-evaluative and affective-perceptual empathy can be distinguished at the level of regional activation.

Abnormal body perception and neural activity in the insula in depression: an fMRI study of the depressed "material me".

OBJECTIVES: In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their "material me". While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the "material me" has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. METHODS: We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. RESULTS: MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. CONCLUSIONS: We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients' somato-vegetative abnormalities and their abnormal "material me".

Decreased neuronal activity in reward circuitry of pathological gamblers during processing of personal relevant stimuli.

Pathological gamblers impress by an increasing preoccupation with gambling, which leads to the neglect of stimuli, interests, and behaviors that were once of high personal relevance. Neurobiologically dysfunctions in reward circuitry underlay pathological gambling. To explore the association of both findings, we investigated 16 unmedicated pathological gamblers using an fMRI paradigm that included two different tasks: the evaluation of personal relevance and a reward task that served as a functional localizer. Pathological gamblers revealed diminished deactivation during monetary loss events in some of our core reward regions, the left nucleus accumbens and the left putamen. Moreover, while pathological gamblers viewed stimuli of high personal relevance, we found decreased neuronal activity in all of our core reward regions, including the bilateral nucleus accumbens and the left ventral putamen cortex as compared to healthy controls. We demonstrated for the first time altered neuronal activity in reward circuitry during personal relevance in pathological gamblers. Our findings may provide new insights into the neurobiological basis of pathological gamblers' preoccupation by gambling.

Is our self nothing but reward? Neuronal overlap and distinction between reward and personal relevance and its relation to human personality.

BACKGROUND: The attribution of personal relevance, i.e. relating internal and external stimuli to establish a sense of belonging, is a common phenomenon in daily life. Although previous research demonstrated a relationship between reward and personal relevance, their exact neuronal relationship including the impact of personality traits remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we applied an experimental paradigm that allowed us to explore the neural response evoked by reward and the attribution of personal relevance separately. We observed different brain regions previously reported to be active during reward and personal relevance, including the bilateral caudate nucleus and the pregenual anterior cingulate cortex (PACC). Additional analysis revealed activations in the right and left insula specific for the attribution of personal relevance. Furthermore, our results demonstrate a negative correlation between signal changes in both the PACC and the left anterior insula during the attribution of low personal relevance and the personality dimension novelty seeking. CONCLUSION/SIGNIFICANCE: While a set of subcortical and cortical regions including the PACC is commonly involved in reward and personal relevance, other regions like the bilateral anterior insula were recruited specifically during personal relevance. Based on our correlation between novelty seeking and signal changes in both regions during personal relevance, we assume that the neuronal response to personally relevant stimuli is dependent on the personality trait novelty seeking.

Decreased neural activity in reward circuitry during personal reference in abstinent alcoholics--a fMRI study.

Two of the most striking features in alcoholism are the irresistible craving for alcohol and the proceeding neglect of other activities and pleasures that were formerly relevant. Craving has been investigated extensively and is commonly due to a dysfunctional reward system. The neural basis of the neglect of self-relevant interests, which can be described as altered personal reference, and its association to the reward system, however, remains unclear. Using fMRI, we investigated neural activity during a paradigm that tested for both reward and personal reference with regard to the same stimuli, i.e., alcoholic and nonalcoholic pictures, in healthy subjects and abstinent alcoholic patients. Alcoholic patients showed slightly reduced signal changes in the brain stem adjacent to ventral tegmental area (VTA) and in the ventromedial prefrontal cortex (VMPFC) during the reward task, while we found no alterations in the right and left ventral striatum (VS). The same regions (VS, VTA, and VMPFC), however, showed reduced signal changes during personal reference with lack of neural differentiation between high and low referenced stimuli in alcoholic patients. In summary, we demonstrate for the first time neurophysiological alterations in reward circuitry during personal reference in alcoholic patients. Our results underline the important role of the reward circuitry during personal reference in the pathophysiology of alcohol addiction.

Self-referential processing in our brain--a meta-analysis of imaging studies on the self.

The question of the self has intrigued philosophers and psychologists for a long time. More recently, distinct concepts of self have also been suggested in neuroscience. However, the exact relationship between these concepts and neural processing across different brain regions remains unclear. This article reviews neuroimaging studies comparing neural correlates during processing of stimuli related to the self with those of non-self-referential stimuli. All studies revealed activation in the medial regions of our brains' cortex during self-related stimuli. The activation in these so-called cortical midline structures (CMS) occurred across all functional domains (e.g., verbal, spatial, emotional, and facial). Cluster and factor analyses indicate functional specialization into ventral, dorsal, and posterior CMS remaining independent of domains. Taken together, our results suggest that self-referential processing is mediated by cortical midline structures. Since the CMS are densely and reciprocally connected to subcortical midline regions, we advocate an integrated cortical-subcortical midline system underlying human self. We conclude that self-referential processing in CMS constitutes the core of our self and is critical for elaborating experiential feelings of self, uniting several distinct concepts evident in current neuroscience.