Cortical regulation of helping behaviour towards others in pain.

Humans and animals exhibit various forms of prosocial helping behaviour towards others in need1-3. Although previous research has investigated how individuals may perceive others' states4,5, the neural mechanisms of how they respond to others' needs and goals with helping behaviour remain largely unknown. Here we show that mice engage in a form of helping behaviour towards other individuals experiencing physical pain and injury-they exhibit allolicking (social licking) behaviour specifically towards the injury site, which aids the recipients in coping with pain. Using microendoscopic imaging, we found that single-neuron and ensemble activity in the anterior cingulate cortex (ACC) encodes others' state of pain and that this representation is different from that of general stress in others. Furthermore, functional manipulations demonstrate a causal role of the ACC in bidirectionally controlling targeted allolicking. Notably, this behaviour is represented in a population code in the ACC that differs from that of general allogrooming, a distinct type of prosocial behaviour elicited by others' emotional stress. These findings advance our understanding of the neural coding and regulation of helping behaviour.

Callousness, exploitativeness, and tracking of cooperation incentives in the human default network.

Human cognitive capacities that enable flexible cooperation may have evolved in parallel with the expansion of frontoparietal cortical networks, particularly the default network. Conversely, human antisocial behavior and trait antagonism are broadly associated with reduced activity, impaired connectivity, and altered structure of the default network. Yet, behaviors like interpersonal manipulation and exploitation may require intact or even superior social cognition. Using a reinforcement learning model of decision-making on a modified trust game, we examined how individuals adjusted their cooperation rate based on a counterpart's cooperation and social reputation. We observed that learning signals in the default network updated the predicted utility of cooperation or defection and scaled with reciprocal cooperation. These signals were weaker in callous (vs. compassionate) individuals but stronger in those who were more exploitative (vs. honest and humble). Further, they accounted for associations between exploitativeness, callousness, and reciprocal cooperation. Separately, behavioral sensitivity to prior reputation was reduced in callous but not exploitative individuals and selectively scaled with responses of the medial temporal subsystem of the default network. Overall, callousness was characterized by blunted behavioral and default network sensitivity to cooperation incentives. Exploitativeness predicted heightened sensitivity to others' cooperation but not social reputation. We speculate that both compassion and exploitativeness may reflect cognitive adaptations to social living, enabled by expansion of the default network in anthropogenesis.

Connected in Bad Times and in Good Times: Empathy Induces Stable Social Closeness.

Humans need social closeness to prosper. There is evidence that empathy can induce social closeness. However, it remains unclear how empathy-related social closeness is formed and how stable it is as time passes. We applied an acquisition-extinction paradigm combined with computational modeling and fMRI, to investigate the formation and stability of empathy-related social closeness. Female participants observed painful stimulation of another person with high probability (acquisition) and low probability (extinction) and rated their closeness to that person. The results of two independent studies showed increased social closeness in the acquisition block that resisted extinction in the extinction block. Providing insights into underlying mechanisms, reinforcement learning modeling revealed that the formation of social closeness is based on a learning signal (prediction error) generated from observing another's pain, whereas maintaining social closeness is based on a learning signal generated from observing another's pain relief. The results of a reciprocity control study indicate that this feedback recalibration is specific to learning of empathy-related social closeness. On the neural level, the recalibration of the feedback signal was associated with neural responses in anterior insula and adjacent inferior frontal gyrus and the bilateral superior temporal sulcus/temporoparietal junction. Together, these findings show that empathy-related social closeness generated in bad times, that is, empathy with the misfortune of another person, transfers to good times and thus may form one important basis for stable social relationships.

Empathy incites a stable prosocial decision bias.

Empathy toward suffering individuals serves as potent driver for prosocial behavior. However, it remains unclear whether prosociality induced by empathy for another person's pain persists once that person's suffering diminishes. To test this, participants underwent functional magnetic resonance imaging while performing a binary social decision task that involved allocation of points to themselves and another person. In block one, participants completed the task after witnessing frequent painful stimulation of the other person, and in block two, after observing low frequency of painful stimulation. Drift-diffusion modeling revealed an increased initial bias toward making prosocial decisions in the first block compared with baseline that persisted in the second block. These results were replicated in an independent behavioral study. An additional control study showed that this effect may be specific to empathy as stability was not evident when prosocial decisions were driven by a social norm such as reciprocity. Increased neural activation in dorsomedial prefrontal cortex was linked to empathic concern after witnessing frequent pain and to a general prosocial decision bias after witnessing rare pain. Altogether, our findings show that empathy for pain elicits a stable inclination toward making prosocial decisions even as their suffering diminishes.

Do we empathize humanoid robots and humans in the same way? Behavioral and multimodal brain imaging investigations.

Humanoid robots have been designed to look more and more like humans to meet social demands. How do people empathize humanoid robots who look the same as but are essentially different from humans? We addressed this issue by examining subjective feelings, electrophysiological activities, and functional magnetic resonance imaging signals during perception of pain and neutral expressions of faces that were recognized as patients or humanoid robots. We found that healthy adults reported deceased feelings of understanding and sharing of humanoid robots' compared to patients' pain. Moreover, humanoid robot (vs. patient) identities reduced long-latency electrophysiological responses and blood oxygenation level-dependent signals in the left temporoparietal junction in response to pain (vs. neutral) expressions. Furthermore, we showed evidence that humanoid robot identities inhibited a causal input from the right ventral lateral prefrontal cortex to the left temporoparietal junction, contrasting the opposite effect produced by patient identities. These results suggest a neural model of modulations of empathy by humanoid robot identity through interactions between the cognitive and affective empathy networks, which provides a neurocognitive basis for understanding human-robot interactions.

Vicarious punishment of moral violations in naturalistic drama narratives predicts cortical synchronization.

Punishment of moral norm violators is instrumental for human cooperation. Yet, social and affective neuroscience research has primarily focused on second- and third-party norm enforcement, neglecting the neural architecture underlying observed (vicarious) punishment of moral wrongdoers. We used naturalistic television drama as a sampling space for observing outcomes of morally-relevant behaviors to assess how individuals cognitively process dynamically evolving moral actions and their consequences. Drawing on Affective Disposition Theory, we derived hypotheses linking character morality with viewers' neural processing of characters' rewards and punishments. We used functional magnetic resonance imaging (fMRI) to examine neural responses of 28 female participants while free-viewing 15 short story summary video clips of episodes from a popular US television soap opera. Each summary included a complete narrative structure, fully crossing main character behaviors (moral/immoral) and the consequences (reward/punishment) characters faced for their actions. Narrative engagement was examined via intersubject correlation and representational similarity analysis. Highest cortical synchronization in 9 specifically selected regions previously implicated in processing moral information was observed when characters who act immorally are punished for their actions with participants' empathy as an important moderator. The results advance our understanding of the moral brain and the role of normative considerations and character outcomes in viewers' engagement with popular narratives.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Predicting psychosocial intervention response from baseline gene expression.

To address the challenge of predicting psychological response to a psychosocial intervention we tested the possibility that baseline gene expression profiles might provide information above and beyond baseline psychometric measures. The genomics strategy utilized individual level inferences of transcription factor activity to predict changes in loneliness and affect in response to two well-established meditation interventions. Initial algorithm development analyses focused on three a-priori defined stress-related gene regulation pathways (CREB, GR, and NF-ĸB) as inferred from TELiS promoter-based bioinformatic analysis of basal (pre-intervention) blood samples from a randomized-controlled trial comparing a compassion-based meditation (CM, n = 45) with mindfulness meditation (MM, n = 44). Greater baseline CREB activity (but not GR or NF-ĸB) predicted greater reductions from pre- to post-intervention in loneliness (b = -0.24, p = 0.016) and negative emotions (b = -0.23, p = 0.017) for CM, but not for MM. A second algorithm validation analysis applied the same approach to another randomized controlled trial comparing CM (n = 42) with MM (n = 38) and a health education control condition (n = 41). Similarly, greater baseline CREB activity predicted greater pre- to post-intervention decreases in loneliness (b = -0.24, p = 0.029) and greater increases in satisfaction with life (b = 0.21, p = 0.046) for the CM condition only. Baseline CREB activity was not associated with baseline psychometric measures in either study. Results raise the possibility that pre-intervention gene expression profiles may reflect non-conscious psychobiological states that affect psychological responses to distinct psychosocial interventions, and thereby help personalize intervention selection.

Acute experimental inflammation in healthy women attenuates empathy for psychological pain.

Administration of low-dose lipopolysaccharide (LPS) to healthy humans is a translational approach to analyze the effects of acute systemic inflammation and sickness behavior. Although studies documented that LPS-induced inflammation can alter social behavior, its impact on empathy remains poorly understood. In this double-blind, placebo-controlled study, 52 healthy female volunteers received an intravenous injection of either LPS (0.4 ng/kg body weight) or placebo and completed the Social Interaction Empathy Task (SIET) two hours after injection. Physiological responses (blood pressure, heart rate, body temperature, cytokines, cortisol) were analyzed along with sickness symptoms and mood before and after LPS or placebo administration. LPS application led to significant increases in plasma cytokines and sickness symptoms as well as low mood. Moreover, volunteers receiving LPS showed significantly less empathy for other's psychological pain than those who received placebo. Furthermore, LPS-injected volunteers with more severe sickness symptoms displayed higher pain ratings in the first-person perspective. Thus, low-grade inflammation reduces empathy for other's psychological pain which might reflect an adaptive strategy to save energy by not responding empathetically when sick oneself.

Testing the monitor and acceptance theory: the role of training-induced changes in monitoring- and acceptance-related capacities after attention-based, socio-emotional, or socio-cognitive mental training in reducing cortisol stress reactivity.

Mindfulness-based interventions have become a popular means to reduce stress. However, the specific mechanisms driving observed stress reduction remain understudied. The Monitor and Acceptance Theory suggests that the cultivation of monitoring and acceptance skills are necessary moderators of practice-induced stress reduction. In the context of the ReSource Project, a large healthy adult sample underwent three 3-month mental training modules targeting either attentional (Presence module), socio-affective (Affect module) or socio-cognitive skills (Perspective module). In the current study, the development of a range of inter-individual differences in mindfulness-, interoception- and compassion-related traits - which mapped to either monitoring or acceptance categories - was tracked. The relationship of these training-induced changes with cortisol stress reactivity after the three distinct 3-month training modules was explored. We found that stress sensitivity was particularly modulated by a differential adaptivity of one cultivated attentional capacity - Attention regulation - which predicted higher cortisol reactivity after mere attention training (Presence) but was associated with lower stress-induced cortisol release after additional socio-affective and socio-cognitive practice (Affect and Perspective). However, this effect did not survive multiple comparisons correction, and analyses were limited by the sample size available. We conclude that our study provides preliminary support of the Monitor and Acceptance Theory, lending weight to the advantage of primary attentional increases in order to fully harness the beneficial effects of socio-affective training, ultimately leading to stress reduction. Although training-induced increases in acceptance were not directly shown to contribute to lowering cortisol stress reactivity, the data suggest an additional benefit of socio-affective and socio-cognitive training that is not directly captured within the current analyses. Our study corroborates the importance of going beyond the training of attention monitoring to foster stress resilience, and highlights that mental training relies on the co-development of several interacting processes to successfully attenuate stress. Further exploring the overarching concept of acceptance in future research may prove beneficial to the theoretical framework of MAT, and in understanding the processes by which stress reduction occurs.

Empathic stress is decreased by prior stressor experience and increased in a position of power.

The observation of a stressed individual can trigger a stress response in a passive observer. Little is known about the mechanisms of this so-termed empathic stress, including the observer's empathic involvement with the stressful situation. In 108 opposite-sex stranger dyads, we expected to increase the observer's empathic involvement with a stressed target performing a standardized laboratory stressor (Trier Social Stress Test, TSST; Kirschbaum et al., 1993) by exposing observers themselves to the TSST one week earlier. Conversely, we intended to decrease empathic involvement by granting observers a powerful position over the targets (by asking them to evaluate the targets' TSST performance and allegedly decide on their financial compensation). A control group without any manipulation was also included. In the preregistered data analysis, two types of empathic stress were investigated: vicarious stress, which evolves irrespective of the target's stress response, and stress resonance, which is proportional to the target's stress response. Irrespective of manipulation, observers exhibited vicarious stress in subjective and high-frequency heart rate variability (HF-HRV), and synchronized with the targets' stress reactivity in cortisol release. Prior TSST experience unexpectedly decreased observers' self-reported empathy and vicarious cortisol stress reactivity. The power manipulation, conversely, led to stronger observer vicarious stress in overall heart rate and HF-HRV reactivity. Based on Wondra and Ellsworth's (2015) appraisal theory, we propose that, due to their prior stressor exposure, observers habituated to said stressor, and consequently changed their evaluation of the target's stressful situation. In contrast, observers in the powerful position may have felt responsible for the targets, triggering a stronger vicarious stressful experience.

Alterations in metabolites in the anterior cingulate cortex and thalamus and their associations with pain and empathy in patients with chronic mild pain: a preliminary study.

Proton magnetic resonance spectroscopy (1H-MRS) has shown inconsistent alterations in the brain metabolites of individuals with chronic pain. We used 3T 1H-MRS to investigate the brain metabolites in the anterior cingulate cortex and thalamus of 22 patients with chronic mild pain and no gait disturbance and 22 healthy controls. The chronic-pain group included patients with chronic low back pain and/or osteoarthritis but none suffering from hypersensitivity. There were no significant between group-differences in glutamate, glutamate plus glutamine (Glx), N-acetylaspartate, glycerophosphorylcholine (GPC), glutamine, creatine plus phosphocreatine, or myo-inositol in the anterior cingulate cortex, but the patients showed a significant decrease in GPC, but not other metabolites, in the thalamus compared to the controls. The GPC values in the patients' thalamus were significantly correlated with pain components on the Short-Form McGill Pain Questionnaire (SF-MPQ-2) and affective empathy components on the Questionnaire of Cognitive and Affective Empathy (QCAE). The GPC in the patients' anterior cingulate cortex showed significant correlations with cognitive empathy components on the QCAE. Myo-inositol in the controls' anterior cingulate cortex and Glx in the patients' thalamus each showed significant relationships with peripheral responsivity on the QCAE. These significances were not significant after Bonferroni corrections. These preliminary findings indicate important roles of GPC, myo-inositol, and Glx in the brain of patients with chronic mild pain.

Reduced prosocial motivation and effort in adolescents with conduct problems and callous-unemotional traits.

BACKGROUND: Prosocial behaviours - acts that benefit others - are of crucial importance for many species including humans. However, adolescents with conduct problems (CP), unlike their typically developing (TD) peers, demonstrate markedly reduced engagement in prosocial behaviours. This pattern is particularly pronounced in adolescents with CP and high levels of callous-unemotional traits (CP/HCU) who are at increased risk of developing psychopathy in adulthood. While a substantial amount of research has investigated the cognitive-affective mechanisms thought to underlie antisocial behaviour, much less is known about the mechanisms that could explain reduced prosocial behaviours in adolescents with CP. METHODS: Here we examined the willingness to exert effort to benefit oneself (self) and another person (other, prosocial condition) in children with CP/HCU, CP and lower levels of CU traits (CP/LCU) and their TD peers. The task captured both prosocial choices, and actual effort exerted following prosocial choices, in adolescent boys aged 11-16 (27 CP/HCU; 34 CP/LCU; 33 TD). We used computational modelling to reveal the mechanistic processes involved when choosing prosocial acts. RESULTS: We found that both CP/HCU and CP/LCU groups were more averse to initiating effortful prosocial acts than TD adolescents - both at a cognitive and at a behavioural level. Strikingly, even if they chose to initiate a prosocial act, the CP/HCU group exerted less effort following this prosocial choice than other groups. CONCLUSIONS: Our findings indicate that reduced exertion of effort to benefit others may be an important factor that differentiates adolescents with CP/HCU from their peers with CP/LCU. They offer new insights into what might drive low prosocial behaviour in adolescents with CP, including vulnerabilities that may particularly characterise those with high levels of CU traits.

Oxytocin neurons in the paraventricular nucleus and fear empathy among male mice.

BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.

Compassionate mind training for people with Parkinson's disease: A pilot study and predictors of response.

INTRODUCTION: People with Parkinson's disease (PD) often present with disabling neuropsychiatric symptoms. Compassionate mind training (CMT) is a psychological approach effective in reducing stress and promoting psychological well-being. Heart rate variability (HRV), a measure reflecting sympathovagal balance, has been associated with psychological well-being and a compassionate attitude. AIM: To assess the feasibility and effectiveness of CMT in enhancing the quality of life and psychological well-being in PD patients. Additionally, we evaluated HRV as a physiomarker for assessing the CMT outcomes. METHODS: Twenty-four PD patients participated in the study. A 6-week online CMT intervention was delivered on a weekly basis. At baseline and post-intervention patients completed questionnaires assessing depression, anxiety and quality of life. In a subsample of 11 patients, HRV was measured at baseline and post-intervention in three conditions: at rest, during stress and after 3 min of deep breathing. RESULTS: The attendance rate was 94.3%. Quality of life and perceived stigma improved post-intervention as compared with baseline (p = 0.02 and p = 0.03 for PD Questionnaire-39 total score and Stigma subscore, respectively). After CMT, patients presented better physiological regulation to stress, as measured by higher HRV as compared with baseline (p = 0.005). Notably, patients who were more resilient to stress at baseline (less decrease in HRV during stress) experienced a more substantial reduction in anxiety and depression following CMT. CONCLUSIONS: CMT is feasible and can improve quality of life and stigma in PD patients. HRV emerges as a promising physiomarker for predicting and measuring the outcomes of psychological interventions in PD.

Interoceptive awareness mediated the effects of a 15-minute diaphragmatic breathing on empathy for pain: A randomized controlled trial.

Although empathy for pain plays an important role in positive interpersonal relationships and encourages engagement in prosocial behavior, it remains largely unknown whether empathy for pain could be effectively altered by psychophysiological techniques. This study aimed to investigate the impact of a single session of diaphragmatic breathing practice on empathy for pain and examine the potential mechanism involving interoceptive awareness. A total of 66 healthy participants were randomly assigned to the intervention group or the control group. The intervention group received a 15-minute diaphragmatic breathing (DB) practice with real-time biofeedback, while the control group was to gaze at a black screen at rest and not engaged in any other activities. Before and after the invention, all participants were instructed to evaluate the intensity and unpleasantness of empathy for pain while watching different pictures with pain or non-pain conditions. The Multidimensional Assessment of Interoceptive Awareness (MAIA) was then administered to measure interoceptive awareness. The results indicated a significant interaction between group and time with regard to empathy for pain and MAIA. The DB group showed a statistically significant decrease in both pain intensity and unpleasantness during the pain picture condition, as well as a noteworthy increase in MAIA scores. The control group did not demonstrate any substantial changes. More importantly, the regulation of attention, a dimension of MAIA, had a significant mediating effect on the impact of diaphragmatic breathing on reported unpleasantness. Diaphragmatic breathing could serve as a simple, convenient, and practical strategy to optimize human empathy for pain that warrants further investigation, which has important implications not only for individuals with impaired empathy for pain but also for the improvement of interoceptive awareness.

Topographic mapping of the sensorimotor qualities of empathic reactivity: A psychophysiological study in people with spinal cord injuries.

The experience of empathy for pain is underpinned by sensorimotor and affective dimensions which, although interconnected, are at least in part behaviorally and neurally distinct. Spinal cord injuries (SCI) induce a massive, below-lesion level, sensorimotor body-brain disconnection. This condition may make it possible to test whether sensorimotor deprivation alters specific dimensions of empathic reactivity to observed pain. To explore this issue, we asked SCI people with paraplegia and healthy controls to observe videos of painful or neutral stimuli administered to a hand (intact) or a foot (deafferented). The stimuli were displayed by means of a virtual reality set-up and seen from a first person (1PP) or third person (3PP) visual perspective. A number of measures were recorded ranging from explicit behaviors like explicit verbal reports on the videos, to implicit measures of muscular activity (like EMG from the corrugator and zygomatic muscles that may represent a proxy of sensorimotor empathy) and of autonomic reactivity (like the electrodermal response and Respiratory Sinus Arrhythmia that may represent a general proxy of affective empathy). While no across group differences in explicit verbal reports about the pain stimuli were found, SCI people exhibited reduced facial muscle reactivity to the stimuli applied to the foot (but not the hand) seen from the 1PP. Tellingly, the corrugator activity correlated with SCI participants' neuropathic pain. There were no across group differences in autonomic reactivity suggesting that SCI lesions may affect sensorimotor dimensions connected to empathy for pain.

Moving on with (social) cognition in idiopathic cervical dystonia.

OBJECTIVE: Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients. METHOD: In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy). RESULTS: CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC. CONCLUSIONS: The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

Sensitivity to moral and conventional rules in temporal lobe epilepsy.

OBJECTIVES: Sensitivity to moral and conventional rules (SMCR) is supported by bilateral brain networks and psychosocial input both of which may be altered in temporal lobe epilepsy (TLE). This study evaluated the components of SMCR in patients with TLE, aiming to clarify their preservation and link to psychopathological and cognitive aspects. METHODS: Adult patients with unilateral TLE and healthy controls were evaluated using neuropsychological tests for SMCR, memory, language, and executive functions, the Empathy Questionnaire (EQ), and the Symptom Checklist-90-R (SCL-90-R). RESULTS: The SMCR test items showed good reliability and validity, yielding the Severity and Rules factors distinct from the Executive, Lexical and Memory factors. Patients with right TLE scored worse in moral rules recognition than controls, but this difference was nullified by a significant influence for age and sex. The Severity and Rules factors related to semantic fluency and age and, respectively, TLE side and psychoticism. However, these factors did predict TLE membership. CONCLUSIONS: In adult patients with TLE, the SMCR test reflects a distinct cognitive domain. Conventional rules are well-retained, while moral reasoning may be only affected in right TLE if unfavorable demographics coexist. Although age, TLE side, semantic abilities, and psychoticism cooperate to determine SMCR, impairment of such domain is not a distinctive feature of TLE.

Virtual Reality Combined With Psychoeducation to Improve Emotional Well-Being in Informal Caregivers of Alzheimer's Disease Patients: Rationale and Study Design of a Randomized Controlled Trial.

OBJECTIVES: Care for community-dwelling people with dementia is frequently delegated to relatives, who find themselves in the role of informal caregivers with no practical management knowledge. This situation exposes caregivers to increased risk for emotional wellbeing. The current study aims to test whether the integration of the efficacy of an immersive virtual reality (VR) experience into an online psychoeducational program impacts caregiver empathy and therefore emotional wellbeing. METHODS: One-hundred informal caregivers of mild-to-moderate Alzheimer's disease (AD) patients will be enrolled and randomly assigned to (i) an online psychoeducational program (control arm); or (ii) an online psychoeducational program integrated with VR (experimental arm). VR will consist of 360-degree videos involving the caregivers to an immersive experience of dementia symptoms from the patient's perspective. Before, after the intervention and after 2 months, all participants will complete validated clinical scales for caregiver burden and anxiety (primary outcomes) and sense of competence and dispositional empathy (secondary outcomes). A subsample of 50 participants will also undergo MRI exam, including structural and functional (resting-state and task-functional MRI [fMRI]) sequences. The fMRI task paradigm will use emotional stimuli to evaluate the neural correlate of empathy, by stressing its cognitive and affective components. The main outcome will be the change in the clinical assessment; the secondary outcome will be the change in brain connectivity of networks subserving the empathic and emotional functioning. RESULTS: We expect that the psychoeducational program will decrease anxiety and stress, enabling caregivers to perceive themselves capable of managing AD patients at home, educating them on symptom handling and boosting their cognitive empathy. In the experimental intervention, the VR-based experience will act as an add-on to psychoeducation, leading to greater improvement in the assessed clinical dimensions. VR should, in fact, enable a deeper understanding of disease symptoms and improve caregivers' cognitive empathy. We expect that the experimental intervention will result in deeper comprehension of disease symptoms and further strengthen caregivers' cognitive empathy. At the neural level, we expect to observe increased activation in circuits subserving cognitive empathy and decreased activation in circuits underlying affective empathy. CONCLUSIONS: To the best of our knowledge, this will be the first randomized controlled trial assessing the effect of combining psychoeducational interventions with VR-based experience in caregivers, and assessing both clinical and imaging outcomes. TRIAL REGISTRATION: Registered in ClinicalTrials.gov (NCT05780476).