Samantha V. Abram

Self-reported empathy deficits are uniquely associated with poor functioning in schizophrenia

BACKGROUND Social cognitive deficits have been proposed to be among the causes of poor functional outcome in schizophrenia. Empathy, or sharing and understanding the unique emotions and experiences of other people, is one of the key elements of social cognition, and prior studies suggest that empathic processes are impaired in schizophrenia. The current study examined whether impairments in self-reported empathy were associated with poor functioning, above and beyond the influences of neurocognitive deficits and psychopathology. METHODS Individuals with schizophrenia (n=46) and healthy controls (n=37) completed the Interpersonal Reactivity Index (IRI), a measure of emotional and cognitive empathy. Participants also completed a neuropsychological test battery, clinical ratings of psychopathology, and functional outcome measures assessing both functional capacity and community functioning. After testing for between-group differences, we assessed the relationships between self-reported empathy and the measures of functioning, neurocognition, and psychopathology. Regression analyses examined whether empathic variables predicted functional outcomes. RESULTS Individuals with schizophrenia reported lower IRI scores for perspective-taking and empathic concern, and higher IRI scores for personal distress than controls. Among individuals with schizophrenia, lower perspective-taking, greater disorganized symptoms, and deficits in working memory and episodic memory were correlated with poorer functional capacity and community functioning. Lower scores for perspective-taking explained significant incremental variance in both functional capacity (ΔR(2)=.09, p<.05) and community functioning (ΔR(2)=.152, p<.01) after accounting for relevant neurocognitive and psychopathological variables. CONCLUSIONS Impaired perspective-taking, a component of cognitive empathy, is associated with poor functioning even after taking into account the influences of neurocognitive deficits and psychopathology. These findings support further efforts to clarify the underlying causes of empathic disturbances and suggest that treatments for these disturbances may help functional recovery in schizophrenia.

Alterations in Brain Activation During Cognitive Empathy Are Related to Social Functioning in Schizophrenia

Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response.

Functional Coherence of Insula Networks is Associated with Externalizing Behavior

The externalizing spectrum encompasses a range of maladaptive behaviors, including substance-use problems, impulsivity, and aggression. Although previous literature has linked externalizing behaviors with prefrontal and amygdala abnormalities, recent studies suggest insula functionality is implicated. This study investigated the relation between insula functional coherence and externalizing in a large community sample (N = 244). Participants underwent a resting functional MRI scan. Three nonartifactual intrinsic connectivity networks (ICNs) substantially involving the insula were identified after completing independent components analysis. Three externalizing domains-general disinhibition, substance abuse, and callous aggression-were measured with the Externalizing Spectrum Inventory. Regression models tested whether within-network coherence for the 3 insula ICNs was related to each externalizing domain. Posterior insula coherence was positively associated with general disinhibition and substance abuse. Anterior insula/ventral striatum/anterior cingulate network coherence was negatively associated with general disinhibition. Insula coherence did not relate to the callous aggression domain. Follow-up analyses indicated specificity for insula ICNs in their relation to general disinhibition and substance abuse as compared with other frontal and limbic ICNs. This study found insula network coherence was significantly associated with externalizing behaviors in community participants. Frontal and limbic ICNs containing less insular cortex were not related to externalizing. Thus, the neural synchrony of insula networks may be central for understanding externalizing psychopathology.

Accurate perception of negative emotions predicts functional capacity in schizophrenia

Several studies suggest facial affect perception (FAP) deficits in schizophrenia are linked to poorer social functioning. However, whether reduced functioning is associated with inaccurate perception of specific emotional valence or a global FAP impairment remains unclear. The present study examined whether impairment in the perception of specific emotional valences (positive, negative) and neutrality were uniquely associated with social functioning, using a multimodal social functioning battery. A sample of 59 individuals with schizophrenia and 41 controls completed a computerized FAP task, and measures of functional capacity, social competence, and social attainment. Participants also underwent neuropsychological testing and symptom assessment. Regression analyses revealed that only accurately perceiving negative emotions explained significant variance (7.9%) in functional capacity after accounting for neurocognitive function and symptoms. Partial correlations indicated that accurately perceiving anger, in particular, was positively correlated with functional capacity. FAP for positive, negative, or neutral emotions were not related to social competence or social attainment. Our findings were consistent with prior literature suggesting negative emotions are related to functional capacity in schizophrenia. Furthermore, the observed relationship between perceiving anger and performance of everyday living skills is novel and warrants further exploration.

Default mode functional connectivity is associated with social functioning in schizophrenia.

Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, the authors used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n = 28) and controls (n = 32). The authors also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity and these measures of social functioning. Results revealed that DMN connectivity did not differ between individuals with schizophrenia and controls. However, connectivity between the mPFC and PCC hubs was significantly associated with social competence and social attainment in individuals with schizophrenia but not in controls as reflected by a significant group-by-connectivity interaction. Social cognition did not mediate the association between DMN connectivity and social functioning in individuals with schizophrenia. The findings suggest that fronto-parietal DMN connectivity in particular may be differentially associated with social functioning in schizophrenia and controls. As a result, DMN connectivity may be used as a neuroimaging marker to monitor treatment response or as a potential target for interventions that aim to enhance social functioning in schizophrenia.

Fronto-temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting‐state functional connectivity between data‐driven networks, or components (referred to as, inter‐component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter‐component connectivity at rest using a group‐matched schizophrenia and control sample. We then assessed whether inter‐component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity‐symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter‐component connectivity, a medial‐fronto‐temporal metric and an orbito‐fronto‐temporal metric were related to cognitive empathy. Moreover, the medial‐fronto‐temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111–1124, 2017.

Using personality neuroscience to study personality disorder

Personality neuroscience integrates techniques from personality psychology and neuroscience to elucidate the neural basis of individual differences in cognition, emotion, motivation, and behavior. This endeavor is pertinent not only to our understanding of healthy personality variation, but also to the aberrant trait manifestations present in personality disorders and severe psychopathology. In the current review, we focus on the advances and limitations of neuroimaging methods with respect to personality neuroscience. We discuss the value of personality theory as a means to link specific neural mechanisms with various traits (e.g., the neural basis of the “Big Five”). Given the overlap between dimensional models of normal personality and psychopathology, we also describe how researchers can reconceptualize psychopathological disorders along key dimensions, and, in turn, formulate specific neural hypotheses, extended from personality theory. Examples from the borderline personality disorder literature are used to illustrate this approach. We provide recommendations for utilizing neuroimaging methods to capture the neural mechanisms that underlie continuous traits across the spectrum from healthy to maladaptive.

Sensitivity to “sunk costs” in mice, rats, and humans

The impact of time wasted The amount of time already spent on a task influences human choice about whether to continue. This dedicated time, known as the “sunk cost,” reduces the likelihood of giving up the pursuit of a reward, even when there is no indication of likely success. Sweis et al. show that this sensitivity to time invested occurs similarly in mice, rats, and humans (see the Perspective by Brosnan). All three display a resistance to giving up their pursuit of a reward in a foraging context, but only after they have made the decision to pursue the reward. Science, this issue p. 178; see also p. 124 Mice, rats, and humans show similar sensitivity to time invested when making foraging decisions. Sunk costs are irrecoverable investments that should not influence decisions, because decisions should be made on the basis of expected future consequences. Both human and nonhuman animals can show sensitivity to sunk costs, but reports from across species are inconsistent. In a temporal context, a sensitivity to sunk costs arises when an individual resists ending an activity, even if it seems unproductive, because of the time already invested. In two parallel foraging tasks that we designed, we found that mice, rats, and humans show similar sensitivities to sunk costs in their decision-making. Unexpectedly, sensitivity to time invested accrued only after an initial decision had been made. These findings suggest that sensitivity to temporal sunk costs lies in a vulnerability distinct from deliberation processes and that this distinction is present across species.

Personality and Neural Correlates of Mentalizing Ability: Personality and mentalizing ability

Theory of mind, or mentalizing, defined as the ability to reason about anothers mental states, is a crucial psychological function that is disrupted in some forms of psychopathology, but little is known about how individual differences in this ability relate to personality or brain function. One previous study linked mentalizing ability to individual differences in the personality trait Agreeableness. Agreeableness encompasses two major subdimensions: Compassion reflects tendencies toward empathy, prosocial behaviour, and interpersonal concern, whereas Politeness captures tendencies to suppress aggressive and exploitative impulses. We hypothesized that Compassion but not Politeness would be associated with better mentalizing ability. This hypothesis was confirmed in Study 1 (N = 329) using a theory of mind task that required reasoning about the beliefs of fictional characters. Post hoc analyses indicated that the honesty facet of Agreeableness was negatively associated with mentalizing. In Study 2 (N = 217), we examined whether individual differences in mentalizing and related traits were associated with patterns of resting–state functional connectivity in the brain. Performance on the theory of mind task was significantly associated with patterns of connectivity between the dorsal medial and core subsystems of the default network, consistent with evidence implicating these regions in mentalization. Copyright

Bootstrap Enhanced Penalized Regression for Variable Selection with Neuroimaging Data

Recent advances in fMRI research highlight the use of multivariate methods for examining whole-brain connectivity. Complementary data-driven methods are needed for determining the subset of predictors related to individual differences. Although commonly used for this purpose, ordinary least squares (OLS) regression may not be ideal due to multi-collinearity and over-fitting issues. Penalized regression is a promising and underutilized alternative to OLS regression. In this paper, we propose a nonparametric bootstrap quantile (QNT) approach for variable selection with neuroimaging data. We use real and simulated data, as well as annotated R code, to demonstrate the benefits of our proposed method. Our results illustrate the practical potential of our proposed bootstrap QNT approach. Our real data example demonstrates how our method can be used to relate individual differences in neural network connectivity with an externalizing personality measure. Also, our simulation results reveal that the QNT method is effective under a variety of data conditions. Penalized regression yields more stable estimates and sparser models than OLS regression in situations with large numbers of highly correlated neural predictors. Our results demonstrate that penalized regression is a promising method for examining associations between neural predictors and clinically relevant traits or behaviors. These findings have important implications for the growing field of functional connectivity research, where multivariate methods produce numerous, highly correlated brain networks.