Neural patterns associated with mixed valence feelings differ in consistency and predictability throughout the brain.

Mixed feelings, the simultaneous presence of feelings with positive and negative valence, remain an understudied topic. They pose a specific set of challenges due to individual variation, and their investigation requires analtyic approaches focusing on individually self-reported states. We used functional magnetic resonance imaging (fMRI) to scan 27 subjects watching an animated short film chosen to induce bittersweet mixed feelings. The same subjects labeled when they had experienced positive, negative, and mixed feelings. Using hidden-Markov models, we found that various brain regions could predict the onsets of new feeling states as determined by self-report. The ability of the models to identify these transitions suggests that these states may exhibit unique and consistent neural signatures. We next used the subjects' self-reports to evaluate the spatiotemporal consistency of neural patterns for positive, negative, and mixed states. The insula had unique and consistent neural signatures for univalent states, but not for mixed valence states. The anterior cingulate and ventral medial prefrontal cortex had consistent neural signatures for both univalent and mixed states. This study is the first to demonstrate that subjectively reported changes in feelings induced by naturalistic stimuli can be predicted from fMRI and the first to show direct evidence for a neurally consistent representation of mixed feelings.

Brain activity associated with emotion regulation predicts individual differences in working memory ability.

Previous behavioral research has found that working memory is associated with emotion regulation efficacy. However, there has been mixed evidence as to whether the neural mechanisms between emotion regulation and working memory overlap. The present study tested the prediction that individual differences on the working memory subtest of the Weschler Adult Intelligence Scale (WAIS-IV) could be predicted from the pattern of brain activity produced during emotion regulation in regions typically associated with working memory, such as the dorsal lateral prefrontal cortex (dlPFC). A total of 101 participants completed an emotion regulation fMRI task in which they either viewed or reappraised negative images. Participants also completed working memory test outside the scanner. A whole brain covariate analysis contrasting the reappraise negative and view negative BOLD response found that activity in the right dlPFC positively related to working memory ability. Moreover, a multivoxel pattern analysis approach using tenfold cross-validated support vector regression in regions-of-interest associated with working memory, including bilateral dlPFC, demonstrated that we could predict individual differences in working memory ability from the pattern of activity associated with emotion regulation. These findings support the idea that emotion regulation shares underlying cognitive processes and neural mechanisms with working memory, particularly in the dlPFC.

Feelings are Messy: The Feelings We Study in Affective Science Should Be Too.

Affective science has taken up the challenge of building a bridge between basic affective science and practical applications. The articles in the Future of Affective Science issue lay out methodological and conceptual frameworks that allow us to expand affective science into real-world settings and to handle naturalistic methods. Along with these advances, accomplishing this goal will require additionally refocusing the types of experiences we study, and the measures of experience we are interested in. This paper explores the necessity for basic affective science to embrace the messy and complex nature of human emotion in order to bridge the gap between theoretical concepts and real-world applicability. Specifically, this involves studying experiences that do not fit as neatly into dominant conceptual frameworks, such as valenced scales and the most common discrete emotion categories, and that may be more difficult to measure or experimentally control. This makes the gap between affective science and real-world feelings larger. To move the field towards incorporating emotional complexity in an empirical manner, I propose measurement standards that err on the side of less fixed-choice options and using stimuli chosen for their potential to elicit highly complex responses over time within the same individual. Designing studies that can measure these experiences will push emotion theories to explain data they were not originally designed for, likely leading to refinement and collaboration. These approaches will help capture the full spectrum of human emotional experience, leading to a more nuanced and applicable understanding of affective science.

Intrinsic connectivity demonstrates a shared role of the posterior cingulate for cue reactivity in both gambling and cocaine use disorders.

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.

Neural correlates of inhibitory control in the context of infant cry and paternal postpartum mental health.

BACKGROUND: Inhibitory control, a form of self-regulation, may support sensitive parenting, but has been understudied in new fathers despite their pronounced risk for stress and mental health challenges. METHODS: This study probed the neural correlates of inhibitory control and its associations to first-time fathers' postpartum mental health, focusing on depressive symptoms, state anxiety, and perceived stress. Six months after their child's birth, 38 fathers self-reported on their mood, anxiety, and stress, and performed a Go/No-Go fMRI task while listening to three sets of sounds (infant cry, pink noise, and silence). RESULTS: Fathers' behavioral inhibition accuracy was consistent across the sound conditions, but their patterns of neural activation varied. Compared to the pink noise condition, fathers showed heightened engagement in prefrontal regulatory regions when self-regulating during the infant cry and silent conditions. When examining correct trials only, results in visual motor area and primary somatosensory cortex emerged only for infant cry and not for pink noise and silence. Moreover, fathers reporting higher levels of postpartum depression, state anxiety, and perceived stress showed greater activation in prefrontal regions when inhibiting during infant cry or silence. CONCLUSION: This study is the first to underscore the complex interplay between the neural mechanisms related to inhibitory control and postpartum mental health and stress across varied auditory context, laying the groundwork for future research.

Moral reframing of messages about mask-wearing during the COVID-19 pandemic.

When communicating about political issues, messages targeted to resonate with the core values of the receiver may be effective, an approach known as moral reframing. During the COVID-19 pandemic, we tested the relationships between moral values and mask-wearing in a sample (N = 540) of self-identified liberals, conservatives, and moderates in the United States. Anti-mask attitudes were stronger in conservatives, and were associated with increased concerns for in-group loyalty, national identity, and personal liberty. We then crafted messages about the benefits of mask-wearing framed to resonate with these moral concerns, and in a pre-registered study of N = 597 self-identified U.S. conservatives, tested the effect of moral reframing on anti-mask attitudes and behaviors. Messages framed in terms of loyalty, with appeals to the protection of the community and America, were effective in reducing anti-mask beliefs, compared with unrelated control messages and messages delivering purely scientific information, and these changes in belief persisted for at least 1 week. Exploratory analyses showed that participants who saw loyalty-framed messages reported wearing masks in public more frequently in the subsequent week. This study provides evidence that framing messages about health behaviors in terms of group loyalty may be one productive way of communicating with conservative audiences.

Preventing antisocial robots: A pathway to artificial empathy.

Given the accelerating powers of artificial intelligence (AI), we must equip artificial agents and robots with empathy to prevent harmful and irreversible decisions. Current approaches to artificial empathy focus on its cognitive or performative processes, overlooking affect, and thus promote sociopathic behaviors. Artificially vulnerable, fully empathic AI is necessary to prevent sociopathic robots and protect human welfare.

Perspective-taking is associated with increased discriminability of affective states in the ventromedial prefrontal cortex.

Recent work using multivariate-pattern analysis (MVPA) on functional magnetic resonance imaging (fMRI) data has found that distinct affective states produce correspondingly distinct patterns of neural activity in the cerebral cortex. However, it is unclear whether individual differences in the distinctiveness of neural patterns evoked by affective stimuli underlie empathic abilities such as perspective-taking (PT). Accordingly, we examined whether we could predict PT tendency from the classification of blood-oxygen-level-dependent (BOLD) fMRI activation patterns while participants (n = 57) imagined themselves in affectively charged scenarios. We used an MVPA searchlight analysis to map where in the brain activity patterns permitted the classification of four affective states: happiness, sadness, fear and disgust. Classification accuracy was significantly above chance levels in most of the prefrontal cortex and in the posterior medial cortices. Furthermore, participants' self-reported PT was positively associated with classification accuracy in the ventromedial prefrontal cortex and insula. This finding has implications for understanding affective processing in the prefrontal cortex and for interpreting the cognitive significance of classifiable affective brain states. Our multivariate approach suggests that PT ability may rely on the grain of internally simulated affective representations rather than simply the global strength.

Functional Brain Connectivity During Narrative Processing Relates to Transportation and Story Influence.

Engaging with narratives involves a complex array of cognitive and affective processes. These processes make stories persuasive in ways that standard arguments are not, though the underlying reasons for this remain unclear. Transportation theory proposes a potential explanation for this: narratives are processed in a way which makes individuals feel immersed in the world of a story, which in turn leads people to resonate emotionally with the events of the story. Recent fMRI studies have shown that the posterior medial cortex (PMC) and anterior insula (AI) play important roles in understanding the meaning of stories and experiencing the feelings they produce. In this study, we aimed to explore the AI's and PMC's role in narrative processing by measuring their functional connectivity with the rest of the brain during story listening, and how connectivity changes as a function of narrative transportation and the persuasiveness of the story. We analyzed data from 36 right-handed subjects who listened to two stories, obtained from podcasts, inside the fMRI scanner. After the scan, subjects were asked a series of questions, including a measure of how transported into the story they felt, how likely they would be to donate to causes related to the messages of the stories. We used searchlight multivariate pattern analysis (MVPA) to classify functional connectivity maps using seeds in both the AI and PMC and to compare these maps between participants who differed in transportation and prosocial intention. We found that connectivity to various regions successfully distinguished between high and low ratings on each of these behavioral measures with accuracies over 75%. However, only one pattern of connectivity was consistent across both stories: PMC-inferior frontal gyrus connectivity successfully distinguished high and low ratings of narrative transportation in both stories. All other findings were not consistent across stories. Instead, we found that patterns of connectivity may relate more to the specific content of the story rather than to a universal way in which narratives are processed.

Bittersweet: The Neuroscience of Ambivalent Affect.

Ambivalent affective states, such as bittersweetness, nostalgia, and longing, which are felt as having both positive and negative aspects, are an important component of human experience but have received little attention. The most influential theoretical frameworks in affective neuroscience focus largely on univalenced states. As a result, it is not known whether ambivalent affect corresponds to a simultaneously positive and negative valenced state or whether it results from a rapid vacillation between positive and negative states. Here we hypothesize that ambivalent affect involves both mechanisms, that is, rapid vacillation and simultaneity of positive and negative affect, albeit at different neurobiological levels. Rapidly vacillating univalent emotions could give rise to an ambivalent feeling, a mechanism that depends on brainstem nuclei that facilitate rapid action programs of emotional behavior while inhibiting opposing behaviors. This reciprocal inhibition prevents organisms from simultaneously implementing responses to conflicting emotions but also allows for rapid switching between emotions triggered by counterfactual thinking and rapid reappraisal of situations. We propose that as these transitions occur and respective interoceptive information reaches the insular cortex, further processing of this "emotional moment" would allow separate emotional events to be experienced as one "mixed" and integrated feeling.

Diagnostic and Classification Considerations Regarding Gaming Disorder: Neurocognitive and Neurobiological Features.

Video gaming and Internet use have become a part of the everyday lives of many individuals, especially during adolescence. Given the health concerns related to problematic gaming behaviors, gaming disorder (GD) has been included in the version of the 11th edition of The International Classification of Diseases (ICD-11) ratified by the secretariat of the World Health Organization. Given these considerations and others (including debate regarding the most appropriate classification of GD and how best to prevent and treat the condition), there is a need for further research into GD. Specifically, we suggest that researching intermediate phenotypes focusing on cognitive and neurobiological function may help clarify GD's relationships to other addictive disorders and more accurately define their relationships with core and associated features of GD. Overlaps in neural activity, cognitive functioning, and other features suggest that GD shares similarities with gambling and substance-use disorders and may best be classified as an addictive disorder. Individuals with GD differ from those with regular game use (RGU) on neurocognitive levels. However, concerns have been raised with respect to the differences between GD and substance-use disorders in certain dimensional features, such as tolerance. Additionally, it has been argued that differences between GD and RGU may not be fully captured by nomenclature systems like the ICD-11. Nonetheless, individuals seek treatment for help with GD, despite the limited data available for effective treatments. As more data are gathered from investigations of GD, they should be translated into refining criteria for GD and optimizing interventions.

Thinking about thinking: A coordinate-based meta-analysis of neuroimaging studies of metacognitive judgements.

Metacognition supports reflection upon and control of other cognitive processes. Despite metacognition occupying a central role in human psychology, its neural substrates remain underdetermined, partly due to study-specific differences in task domain and type of metacognitive judgement under study. It is also unclear how metacognition relates to other apparently similar abilities that depend on recursive thought such as theory of mind or mentalising. Now that neuroimaging studies of metacognition are more prevalent, we have an opportunity to characterise consistencies in neural substrates identified across different analysis types and domains. Here we used quantitative activation likelihood estimation methods to synthesise findings from 47 neuroimaging studies on metacognition, divided into categories based on the target of metacognitive evaluation (memory and decision-making), analysis type (judgement-related activation, confidence-related activation, and predictors of metacognitive sensitivity), and, for metamemory judgements, temporal focus (prospective and retrospective). A domain-general network, including medial and lateral prefrontal cortex, precuneus, and insula was associated with the level of confidence in self-performance in both decision-making and memory tasks. We found preferential engagement of right anterior dorsolateral prefrontal cortex in metadecision experiments and bilateral parahippocampal cortex in metamemory experiments. Results on metacognitive sensitivity were inconclusive, likely due to fewer studies reporting this contrast. Finally, by comparing our results to meta-analyses of mentalising, we obtain evidence for common engagement of the ventromedial and anterior dorsomedial prefrontal cortex in both metacognition and mentalising, suggesting that these regions may support second-order representations for thinking about the thoughts of oneself and others.

Concomitant use of an active boosted protease inhibitor with enfuvirtide in treatment-experienced, HIV-infected individuals: recent data and consensus recommendations.

Recent data from clinical trials investigating the efficacy of enfuvirtide, a fusion inhibitor, in treatment-experienced patients have revealed that the addition of enfuvirtide (ENF) to an active boosted protease inhibitor regimen doubles the rate of virological response. At week 48 of the TORO studies, 55% of patients previously naive to and receiving lopinavir/ritonavir (LPV/r) with ENF achieved a viral load of <400 copies/mL compared with 24% of patients treated with LPV/r alone. At week 24 of the RESIST studies, 70% of previously ENF-naive patients who took both ENF and tipranavir/ritonavir (TPV/r) achieved a >or=1 log10 reduction in viral load compared with 37% of such patients treated with TPV/r alone. Similarly, concomitant use of TMC114/ritonavir (TMC114/r) with ENF, compared with TMC114/r alone, increased the number of patients with <50 copies/mL from 46% to 64% in a combined 24-week analysis from the POWER trials. Data from these trials suggest that combining one agent from a new class with a new agent from a previously exposed class offers a greater chance of achieving full virological control than either type of agent alone. Undetectable viraemia should be the primary objective for treatment-experienced patients requiring a switch in therapy, and the present data support the combination of an active boosted protease inhibitor with an agent from a new class (e.g., ENF) for triple-class-experienced patients.