Dissociating Empathy From Perspective-Taking: Evidence From Intra- and Inter-Individual Differences Research

Humans have the capacity to share others' emotions, be they positive or negative. Elicited by the observed or imagined emotion of another person, an observer develops a similar emotional state herself. This capacity, empathy, is one of the pillars of social understanding and interaction as it creates a representation of another's inner, mental state. Empathy needs to be dissociated from other social emotions and, crucially, also from cognitive mechanisms of understanding others, the ability to take others' perspective. Here, we describe the conceptual distinctions of these constructs and review behavioral and neural evidence that dissociates them. The main focus of the present review lies on the intraindividual changes in empathy and perspective-taking across the lifespan and on interindividual differences on subclinical and clinical levels. The data show that empathy and perspective-taking recruit distinct neural circuits and can be discerned already during early and throughout adult development. Both capacities also vary substantially between situations and people. Differences can be systematically related to situational characteristics as well as personality traits and mental disorders. The clear distinction of affect sharing from other social emotions like compassion and from cognitive perspective-taking, argues for a clear-cut terminology to describe these constructs. In our view, this speaks against using empathy as an umbrella term encompassing all affective and cognitive routes to understanding others. Unifying the way we speak about these phenomena will help to further research on their underlying mechanisms, psychopathological alterations, and plasticity in training and therapy

Perspective Change and Personality State Variability: An Argument for the Role of Self-Awareness and an Outlook on Bidirectionality (Commentary on Wundrack et al., 2018)

In a recent article, Wundrack et al. (2018) put forward an elaborate and intriguing hypothesis on enhanced perspective-taking (Theory of Mind) ability as a consequence of higher personality state variability. While there is evidence in favor of this hypothesis, the clinical examples of bipolar disorder and borderline personality disorder, as highlighted by the authors, demonstrate that a high state variability can also be accompanied by a lower perspective-taking ability (as commonly observed in these disorders). We suggest that only those state changes which are initiated on a voluntary basis and are accompanied by self-awareness go along with a higher perspective-taking ability. Introducing self-awareness as a moderating factor might help explain seemingly conflicting findings related to the hypothesis proposed in the target article. Moreover, we argue that the direction of causality proposed in the target article is not the only conceivable one, and perspective-taking ability could also be a cause, not just a consequence, of personality state variability. Finally, we provide suggestions on how these hypotheses could be tested in future studies

To feel and think what others feel and think: Functional network reorganization underlies context-changes in naturalistic social cognition

The relationship between empathy and Theory of Mind (ToM) as mental capacities enabling dynamic information processing in social interactions is complex and situation-specific. Reductionist approaches and oversimplified measures of these capacities in the lab do not do this complexity justice. While there is a long-standing research tradition studying the two capacities as independent, recent evidence from naturalistic social tasks shows that under certain task demands, neural networks underlying empathy and ToM-processing do interact. In this exploratory graph-theoretic network analysis, we investigate how neural network organization is dynamically modulated when processing affective and cognitive stimuli in isolation and interaction. In a sample of 143 adults, we used a naturalistic social fMRI video task to explore the modulation of neural network organization in empathy, ToM, and their interaction. Using beta-series correlation, we calculated seed-based functional connectivity and condition-specific voxel-wise degree centrality. During empathic processing, we observed network hubs in the right middle frontal gyrus and angular gyrus and a network encompassing the left superior medial frontal, orbitofrontal cortex, and inferior frontal gyrus during ToM processing. Interestingly, the right middle frontal gyrus also showed the highest voxel-wise degree centrality for the interaction of empathy and ToM. Results from our degree centrality and seed-based functional connectivity analysis show dynamic changes in the overall network configuration underlying the interaction of empathy and ToM. Network hubs underlying empathic processing (right middle frontal gyrus) also mediate the interaction of social affect and cognition, and this effect is driven by the emotional modulation of ToM processing (processing emotional and ToM content simultaneously). These hub areas are situated in highly interconnected networks and have been implicated in domain-specific and domain-general processing, such as attentional control. Bottom-up attentional switching might be an important mechanism driving cross-network interaction, in turn enabling behavioral adaptation to changing environmental demands in naturalistic social cognition

Socio-affective and socio-cognitive risk factors of bipolar disorder: Empathy and Theory of Mind in hypomanic personality

Bipolar disorders (BD) are amongst the leading causes of disability worldwide (Ferrari et al., 2016). In spite of their high prevalence and immense individual as well as economic burden, profound knowledge about characteristic markers of an elevated BD-risk as a prerequisite for early detection and intervention is still lacking. One promising approach to gain insights on this matter lies in the study of healthy at-risk populations regarding illness-related endophenotypes. In the context of mental disorders, endophenotypes reflect behavioral, affective, or cognitive markers that are heritable and potentially identify those who are at greatest risk for prospective illness onset (Gottesman & Gould, 2003). Compared to the study of patients, research on healthy populations allows for investigating potential pre-onset markers with less confounds by past pharmacological or psychotherapeutic interventions or prior affective episodes. In the present study, we investigate impairments in social affect and social cognition as candidate endophenotypes of BD. This is not only due to their undisputed relevance in the pathogenesis of psychiatric disorders in general (van Neerven et al., 2021); importantly, indications of respective impairments have been found in association with euthymic and acute BD (Lima et al., 2018; Samamé, 2013) and as well as with an elevated BD-risk (Kjærstad et al., 2021; Miskowiak et al., 2017). Amongst the various aspects of social affect and social cognition that require deliberate differentiation, we aim to specifically focus on the two core concepts of empathy and theory of mind (ToM): Empathy, on the one hand, is defined as sharing another’s emotional state in a vicarious and isomorphic way while being aware that the other is the source of the emotion (de Vignemont & Singer, 2006; Stietz et al., 2019). ToM, on the other hand, refers to the ability to cognitively represent and reason on others’ mental or affective states (Frith & Frith, 2005; Kanske et al., 2016). From an overall perspective, the current state of research is marked by a general lack of evidence on aberrations in empathy and ToM in individuals at-risk for developing BD. However, findings on BD patients could provide initial indications of potential endophenotypes: To be more precise, if aberrations in empathy and ToM were evident in both acute and euthymic BD, this could indicate those to be independent of mood states and, potentially, constitute disorder-related markers that are present independent of disorder onset. When reviewing previous empirical findings, studies in which euthymic or symptomatic BD patients were compared with healthy control subjects frequently indicate elevated empathy and empathic distress on the one hand (Cusi et al., 2010; Montag et al., 2010; Shamay-Tsoory et al., 2009) and deficits in ToM performance on the other hand (Bora et al., 2016; de Siqueira Rotenberg et al., 2020; Sanamé et al., 2012). However, contradictory and null findings are likewise to be considered (Haag et al., 2016; Lemvigh et al., 2022; Purcell et al., 2013; Seidel et al., 2012). In addition, findings have not consistently indicated aberrations in empathy and ToM to be independent of the affective state; for example, increased empathic distress has become evident during manic but not during depressed states in BD (Bodnar & Rybakowski, 2017), which again adds to the ambiguity of the current state of research. Taken together, it becomes clear that specifics regarding the nature and occurrence of altered empathy and ToM in association with BD are still unknown, which – in addition to the general lack of research on at-risk populations – hampers predictions of BD-risk based on early phenomenology. In the present study, we therefore aim to tackle this research gap by investigating a non-clinical population regarding associations between individual BD-risk and aberrant social affect and cognition. More specifically, against the background of hypomanic personality being one of the strongest prodromal predictors of bipolar conversion (Vieta et al., 2018), we aim to investigate potential associations between individual scores in the Hypomanic Personality Scale (HPS; Eckblad & Chapman, 1986; German version from Meyer et al., 2000) and empathy and ToM. For enquiring the latter two, the EmpaToM task (Kanske et al., 2015) is administered. In this functional magnetic resonance imaging (fMRI) paradigm, naturalistic video stimuli depicting autobiographic narratives which are either emotionally negative or neutral are presented. After each video, participants are asked to rate how they feel and how much compassion they feel for the narrator in the video. Subsequently, a multiple-choice question is presented that either demands ToM or factual reasoning on the contents of the video. Throughout the task, subjects’ neural activity is measured, providing insights into neural correlates of the respective behavioral performance. Data from the EmpaToM are particularly insightful considering the oftentimes subtle precursors of disorder onset that might be differentially evident on a behavioral versus neural level. In order to examine aberrations on a neural level, whole-brain fMRI analyses as well as more targeted region of interest (ROI) analyses will be performed. Aiming to ensure a systematic and targeted selection of relevant ROIs, neuroimaging research on neural activity related to social affect and cognition in general (Schurz et al., 2021), task-specific empathy- and ToM-related neural activity in the EmpaToM task (Kanske et al., 2015), as well as neural aberrations observed in BD patients and at-risk individuals (Maletic & Raison, 2014; Miskowiak et al., 2017) will be jointly considered. Prospectively, elucidating the role of behavioral or neural aberrations in social affect and social cognition could enable a more precise understanding of BD-related endophenotypes. Considering that the oftentimes delayed and error-prone diagnostic processes are associated with symptom exacerbation and higher relapse rates (Kessing et al., 2004; Passos et al., 2016), the imperative need for research for more timely and accurate risk prediction becomes evident. In the long run, by driving towards a more comprehensive and potentially neurobiologically grounded phenotype of BD-risk, the present study contributes to forming the foundation for more differential, longitudinal investigations on risk and resilience mechanisms as a prerequisite for more personalized interventions

Analysis of inflammatory markers and tau deposits in an autopsy series of nine patients with anti-IgLON5 disease

Anti-IgLON5 disease is a rare neurological, probably autoimmune, disorder associated in many cases with a specific tauopathy. Only a few post-mortem neuropathological studies have been reported so far. Little is known about the pathogenic mechanisms that result in neurodegeneration. We investigated the neuropathology of anti-IgLON5 disease and characterized cellular and humoral inflammation. We included nine cases (six of them previously published). Median age of patients was 71 years (53-82 years), the median disease duration was 6 years (0.5-13 years), and the female to male ratio was 5:4. Six cases with a median disease duration of 9 years presented a prominent tauopathy. Five of them had a classical anti-IgLON5-related brainstem tauopathy and another presented a prominent neuronal and glial 4-repeat tauopathy, consistent with progressive supranuclear palsy (PSP). Three cases with short disease duration (median 1.25 years) only showed a primary age-related neurofibrillary pathology. Inflammatory infiltrates of T and B cells were mild to moderate and did not significantly differ between anti-IgLON5 disease cases with or without tauopathy. In contrast, we found an extensive neuropil deposition of IgG4 in the tegmentum of the brainstem, olivary nucleus, and cerebellar cortex that was most prominent in two patients with short disease duration without the typical IgLON5-related tauopathy. The IgG4 deposits were particularly prominent in the cerebellar cortex and in these regions accompanied by mild IgG1 deposits. Activated complement deposition (C9neo) was absent. Our study indicates that IgLON5-related tau pathology occurs in later disease stages and may also present a PSP-phenotype with exclusively 4-repeat neuronal and glial tau pathology. The prominent deposition of anti-IgLON5 IgG4 at predilection sites for tau pathology suggests that anti-IgLON5 antibodies precede the tau pathology. Early start of immunotherapy might prevent irreversible neuronal damage and progression of the disease, at least in a subgroup of patients