Leonie Koban

Separate neural representations for physical pain and social rejection

Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92% and 80% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain- and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N = 91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans.

Transient functional blood flow change in the human brain measured noninvasively by diffusing-wave spectroscopy

Multispeckle diffusing-wave spectroscopy (DWS) is used to measure blood flow transients in the human visual cortex following stimulation by 7.5 Hz full-field and checkerboard flickering. The average decay time tau(d) characterizing the decay of the DWS autocorrelation function shows a biphasic behavior; within about 2 s after stimulation onset, tau(d) increases rapidly to about 6% above the baseline value. At later times, tau(d) slowly decreases and reaches a steady-state value about 5% below the baseline value after about 15 s. The initial increase of the DWS signal suggests a transient reduction of the cortical blood flow velocity shortly after stimulation onset. Measurements of this transient response at different positions over the primary visual cortex show a spatial pattern different from the one measured by electroencephalography.

Effects of social context and predictive relevance on action outcome monitoring

Outcome monitoring is crucial for subsequent adjustments in behavior and is associated with a specific electrophysiological response, the feedback-related negativity (FRN). Besides feedback generated by one’s own action, the performance of others may also be relevant for oneself, and the observation of outcomes for others’ actions elicits an observer FRN (oFRN). To test how these components are influenced by social setting and predictive value of feedback information, we compared event-related potentials, as well as their topographies and neural generators, for performance feedback generated by oneself and others in a cooperative versus competitive context. Our results show that (1) the predictive relevance of outcomes is crucial to elicit an FRN in both players and observers, (2) cooperation increases FRN and P300 amplitudes, especially in individuals with high traits of perspective taking, and (3) contrary to previous findings on gambling outcomes, oFRN components are generated for both cooperating and competing observers, but with smaller amplitudes in the latter. Neural source estimation revealed medial prefrontal activity for both FRN and oFRN, but with additional generators for the oFRN in the dorsolateral and ventral prefrontal cortex, as well as the temporoparietal junction. We conclude that the latter set of brain regions could mediate social influences on action monitoring by representing agency and social relevance of outcomes and are, therefore, recruited in addition to shared prediction error signals generated in medial frontal areas during action outcome observation.

Placebo Analgesia Affects Brain Correlates of Error Processing

Placebo analgesia (PA) is accompanied by decreased activity in pain-related brain regions, but also by greater prefrontal cortex (PFC) activation, which has been suggested to reflect increases in top-down cognitive control and regulation of pain. Here we test whether PA is associated with altered prefrontal monitoring functions that could adjust nociceptive processing to a mismatch between expected and experienced pain. We recorded event-related potentials to response errors in a go/nogo task during placebo vs. a matched control condition. Error commission was associated with two well-described components, the error-related negativity (ERN) and the error positivity (Pe). Results show that the Pe, but not the ERN, was amplified during placebo analgesia compared to the control condition, with neural sources in the lateral and medial PFC. This Pe increase was driven by participants showing a placebo-induced change in pain tolerance, but was absent in the group of non-responders. Our results shed new light on the possible functional mechanisms underlying PA, suggesting a placebo-induced transient change in prefrontal error monitoring and control functions.

The Cognitive Neuroscience of Placebo Effects: Concepts, Predictions, and Physiology

Placebos have been used ubiquitously throughout the history of medicine. Expectations and associative learning processes are important psychological determinants of placebo effects, but their underlying brain mechanisms are only beginning to be understood. We examine the brain systems underlying placebo effects on pain, autonomic, and immune responses. The ventromedial prefrontal cortex (vmPFC), insula, amygdala, hypothalamus, and periaqueductal gray emerge as central brain structures underlying placebo effects. We argue that the vmPFC is a core element of a network that represents structured relationships among concepts, providing a substrate for expectations and a conception of the situation-the self in context-that is crucial for placebo effects. Such situational representations enable multidimensional predictions, or priors, that are combined with incoming sensory information to construct percepts and shape motivated behavior. They influence experience and physiology via descending pathways to physiological effector systems, including the spinal cord and other peripheral organs.

What’s in a word? How instructions, suggestions, and social information change pain and emotion

HIGHLIGHTSInstructions and social information have powerful effects on emotion and pain.Physiological and brain responses mirror experienced and behavioral effects.Changes in expectations and appraisal are key mediators of instruction effects.Prefrontal systems may bias affective processing based on instructions. ABSTRACT Instructions, suggestions, and other types of social information can have powerful effects on pain and emotion. Prominent examples include observational learning, social influence, placebo, and hypnosis. These different phenomena and their underlying brain mechanisms have been studied in partially separate literatures, which we discuss, compare, and integrate in this review. Converging findings from these literatures suggest that (1) instructions and social information affect brain systems associated with the generation of pain and emotion, and with reinforcement learning, and that (2) these changes are mediated by alterations in prefrontal systems responsible for top‐down control and the generation of affective meaning. We argue that changes in expectation and appraisal, a process of assessing personal meaning and implications for wellbeing, are two potential key mediators of the effects of instructions and social information on affective experience. Finally, we propose a tentative model of how prefrontal regions, especially dorsolateral and ventromedial prefrontal cortex may regulate affective processing based on instructions and socially transmitted expectations more broadly.

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

Social anxiety is characterized by biased learning about performance and the self.

People learn about their self from social information, and recent work suggests that healthy adults show a positive bias for learning self-related information. In contrast, social anxiety disorder (SAD) is characterized by a negative view of the self, yet what causes and maintains this negative self-view is not well understood. Here the authors use a novel experimental paradigm and computational model to test the hypothesis that biased social learning regarding self-evaluation and self-feelings represents a core feature that distinguishes adults with SAD from healthy controls. Twenty-one adults with SAD and 35 healthy controls (HCs) performed a speech in front of 3 judges. They subsequently evaluated themselves and received performance feedback from the judges and then rated how they felt about themselves and the judges. Affective updating (i.e., change in feelings about the self over time, in response to feedback from the judges) was modeled using an adapted Rescorla-Wagner learning model. HCs demonstrated a positivity bias in affective updating, which was absent in SAD. Further, self-performance ratings revealed group differences in learning from positive feedback—a difference that endured at an average of 1 year follow up. These findings demonstrate the presence and long-term endurance of positively biased social learning about the self among healthy adults, a bias that is absent or reversed among socially anxious adults.

Brain Predictors of Individual Differences in Placebo Responding

Abstract Placebo responses are highly variable across individuals. Explaining this variability is one of the keys to understanding endogenous regulatory processes, and is critical for measuring and controlling placebo effects in all kinds of studies. In this chapter, we review literature on the personality and brain correlates of individual differences in placebo analgesia. An emerging brain literature has used functional magnetic resonance imaging (fMRI), opioid binding, dopamine binding, and structural brain imaging to predict the magnitude of individual placebo responses. Brain predictors in prefrontal cortices and ventral striatum/nucleus accumbens are relatively consistent across studies and methodologies, showing promise for understanding the neural bases of placebo analgesia. However, most studies use voxel-wise correlation maps to relate brain measures and placebo analgesia, which do not provide unbiased measures of predictive accuracy. Thus, the utility of these brain measures remains to be determined by larger-scale studies using appropriate analytic methods. Finally, we address an apparent paradox in the placebo literature: placebo responses appear to be both related to stable person-level variables (e.g. brain structure, genetics, personality) and highly variable across situational contexts. We suggest that a resolution lies in recognizing that placebo responses, like many other psychologic phenomena, arise from person × situation interactions, and that both must be considered jointly in order to understand and predict who will be a placebo ‘responder’ in a given situation.

Frontal-brainstem pathways mediating placebo effects on social rejection

Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience, social pain elicited by a recent romantic rejection. We compared these effects with placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared with control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems. SIGNIFICANCE STATEMENT Placebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for nonspecific treatment effects across a wide range of therapeutic approaches and mental health conditions.