The blushing brain: neural substrates of cheek temperature increase in response to self-observation.

Darwin proposed that blushing-the reddening of the face owing to heightened self-awareness-is 'the most human of all expressions'. Yet, relatively little is known about the underlying mechanisms of blushing. Theories diverge on whether it is a rapid, spontaneous emotional response that does not involve reflection upon the self or whether it results from higher-order socio-cognitive processes. Investigating the neural substrates of blushing can shed light on the mental processes underlying blushing and the mechanisms involved in self-awareness. To reveal neural activity associated with blushing, 16-20 year-old participants (n = 40) watched pre-recorded videos of themselves (versus other people as a control condition) singing karaoke in a magnetic resonance imaging scanner. We measured participants' cheek temperature increase-an indicator of blushing-and their brain activity. The results showed that blushing is higher when watching oneself versus others sing. Those who blushed more while watching themselves sing had, on average, higher activation in the cerebellum (lobule V) and the left paracentral lobe and exhibited more time-locked processing of the videos in early visual cortices. These findings show that blushing is associated with the activation of brain areas involved in emotional arousal, suggesting that it may occur independently of higher-order socio-cognitive processes. Our results provide new avenues for future research on self-awareness in infants and non-human animals.

A multivariate brain signature for reward.

The processing of reinforcers and punishers is crucial to adapt to an ever changing environment and its dysregulation is prevalent in mental health and substance use disorders. While many human brain measures related to reward have been based on activity in individual brain regions, recent studies indicate that many affective and motivational processes are encoded in distributed systems that span multiple regions. Consequently, decoding these processes using individual regions yields small effect sizes and limited reliability, whereas predictive models based on distributed patterns yield larger effect sizes and excellent reliability. To create such a predictive model for the processes of rewards and losses, termed the Brain Reward Signature (BRS), we trained a model to predict the signed magnitude of monetary rewards on the Monetary Incentive Delay task (MID; N = 39) and achieved a highly significant decoding performance (92% for decoding rewards versus losses). We subsequently demonstrate the generalizability of our signature on another version of the MID in a different sample (92% decoding accuracy; N = 12) and on a gambling task from a large sample (73% decoding accuracy, N = 1084). We further provided preliminary data to characterize the specificity of the signature by illustrating that the signature map generates estimates that significantly differ between rewarding and negative feedback (92% decoding accuracy) but do not differ for conditions that differ in disgust rather than reward in a novel Disgust-Delay Task (N = 39). Finally, we show that passively viewing positive and negatively valenced facial expressions loads positively on our signature, in line with previous studies on morbid curiosity. We thus created a BRS that can accurately predict brain responses to rewards and losses in active decision making tasks, and that possibly relates to information seeking in passive observational tasks.

Bidirectional cingulate-dependent danger information transfer across rats.

Social transmission of freezing behavior has been conceived of as a one-way phenomenon in which an observer "catches" the fear of another. Here, we use a paradigm in which an observer rat witnesses another rat receiving electroshocks. Bayesian model comparison and Granger causality show that rats exchange information about danger in both directions: how the observer reacts to the demonstrator's distress also influences how the demonstrator responds to the danger. This was true to a similar extent across highly familiar and entirely unfamiliar rats but is stronger in animals preexposed to shocks. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. Using simulations, we support the notion that the coupling of freezing across rats could be selected for to more efficiently detect dangers in a group, in a way similar to cross-species eavesdropping.

Obeying orders reduces vicarious brain activation towards victims' pain.

Past historical events and experimental research have shown complying with the orders from an authority has a strong impact on people's behaviour. However, the mechanisms underlying how obeying orders influences moral behaviours remain largely unknown. Here, we test the hypothesis that when male and female humans inflict a painful stimulation to another individual, their empathic response is reduced when this action complied with the order of an experimenter (coerced condition) in comparison with being free to decide to inflict that pain (free condition). We observed that even if participants knew that the shock intensity delivered to the 'victim' was exactly the same during coerced and free conditions, they rated the shocks as less painful in the coerced condition. MRI results further indicated that obeying orders reduced activity associated with witnessing the shocks to the victim in the ACC, insula/IFG, TPJ, MTG and dorsal striatum (including the caudate and the putamen) as well as neural signatures of vicarious pain in comparison with being free to decide. We also observed that participants felt less responsible and showed reduced activity in a multivariate neural guilt signature in the coerced than in the free condition, suggesting that this reduction of neural response associated with empathy could be linked to a reduction of felt responsibility and guilt. These results highlight that obeying orders has a measurable influence on how people perceive and process others' pain. This may help explain how people's willingness to perform moral transgressions is altered in coerced situations.

Does higher sampling rate (multiband + SENSE) improve group statistics - An example from social neuroscience block design at 3T.

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3 â€‹T scanner using five sequences, up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movie blocks showing complex actions with hand object interactions and (ii) control movie blocks without hand object interaction. Data were processed using a widely used analysis pipeline implemented in SPM12 including the unified segmentation and canonical HRF modelling. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7 â€‹mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.

Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia.

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programmes. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using functional MRI, we show here that observing goal-directed hand actions of others bilaterally recruits lobules VI, VIIb and VIIIa in the cerebellar hemispheres. Moreover, whereas healthy subjects (n = 31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n = 21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients' deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition.

Primary somatosensory cortex necessary for the perception of weight from other people's action: A continuous theta-burst TMS experiment.

The presence of a network of areas in the parietal and premotor cortices, which are active both during action execution and observation, suggests that we might understand the actions of other people by activating those motor programs for making similar actions. Although neurophysiological and imaging studies show an involvement of the somatosensory cortex (SI) during action observation and execution, it is unclear whether SI is essential for understanding the somatosensory aspects of observed actions. To address this issue, we used off-line transcranial magnetic continuous theta-burst stimulation (cTBS) just before a weight judgment task. Participants observed the right hand of an actor lifting a box and estimated its relative weight. In counterbalanced sessions, we delivered sham and active cTBS over the hand region of the left SI and, to test anatomical specificity, over the left motor cortex (M1) and the left superior parietal lobule (SPL). Active cTBS over SI, but not over M1 or SPL, impaired task performance relative to sham cTBS. Moreover, active cTBS delivered over SI just before participants were asked to evaluate the weight of a bouncing ball did not alter performance compared to sham cTBS. These findings indicate that SI is critical for extracting somatosensory features (heavy/light) from observed action kinematics and suggest a prominent role of SI in action understanding.

Mentalizing and the Role of the Posterior Superior Temporal Sulcus in Sharing Others' Embarrassment.

The experience of embarrassment provides a highly salient cue for the human moral apparatus. Interestingly, people also experience embarrassment on behalf of others' inappropriate conditions. The perceiver's embarrassment often lacks an equivalent expression of embarrassment in the social counterpart. The present study examines this phenomenon and distinguishes neural circuits involved in embarrassment with and embarrassment for another person's mishaps. Using functional magnetic resonance imaging, we show that the embarrassment on behalf of others engages the temporal pole and the medial prefrontal cortex, central structures of the mentalizing network, together with the anterior insula and anterior cingulate cortex. In contrast, sharing others' embarrassment additionally stimulated the posterior superior temporal sulcus (STS), which exhibited increased functional integration with inferior parietal and insular cortex areas. These findings characterize common neural circuits involved in the embodied representation of embarrassment and further unravel the unique role of the posterior STS in sharing others' affective state.

Responsibility modulates pain-matrix activation elicited by the expressions of others in pain.

Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured.

cTBS delivered to the left somatosensory cortex changes its functional connectivity during rest.

The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI.

Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.

Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life.

Somatosensation in social perception.

The discovery of mirror neurons in motor areas of the brain has led many to assume that our ability to understand other people's behaviour partially relies on vicarious activations of motor cortices. This Review focuses the limelight of social neuroscience on a different set of brain regions: the somatosensory cortices. These have anatomical connections that enable them to have a role in visual and auditory social perception. Studies that measure brain activity while participants witness the sensations, actions and somatic pain of others consistently show vicarious activation in the somatosensory cortices. Neuroscientists are starting to understand how the brain adds a somatosensory dimension to our perception of other people.

Primary somatosensory cortex discriminates affective significance in social touch.

Another person's caress is one of the most powerful of all emotional social signals. How much the primary somatosensory cortices (SIs) participate in processing the pleasantness of such social touch remains unclear. Although ample empirical evidence supports the role of the insula in affective processing of touch, here we argue that SI might be more involved in affective processing than previously thought by showing that the response in SI to a sensual caress is modified by the perceived sex of the caresser. In a functional MRI study, we manipulated the perceived affective quality of a caress independently of the sensory properties at the skin: heterosexual males believed they were sensually caressed by either a man or woman, although the caress was in fact invariantly delivered by a female blind to condition type. Independent analyses showed that SI encoded, and was modulated by, the visual sex of the caress, and that this effect is unlikely to originate from the insula. This suggests that current models may underestimate the role played by SI in the affective processing of social touch.

Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy.

Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts.

Hebbian Learning is about contingency, not contiguity, and explains the emergence of predictive mirror neurons.

Hebbian Learning should not be reduced to contiguity, as it detects contingency and causality. Hebbian Learning accounts of mirror neurons make predictions that differ from associative learning: Through Hebbian Learning, mirror neurons become dynamic networks that calculate predictions and prediction errors and relate to ideomotor theories. The social force of imitation is important for mirror neuron emergence and suggests canalization.

Predictive coding for the actions and emotions of others and its deficits in autism spectrum disorders.

Traditionally, the neural basis of social perception has been studied by showing participants brief examples of the actions or emotions of others presented in randomized order to prevent participants from anticipating what others do and feel. This approach is optimal to isolate the importance of information flow from lower to higher cortical areas. The degree to which feedback connections and Bayesian hierarchical predictive coding contribute to how mammals process more complex social stimuli has been less explored, and will be the focus of this review. We illustrate paradigms that start to capture how participants predict the actions and emotions of others under more ecological conditions, and discuss the brain activity measurement methods suitable to reveal the importance of feedback connections in these predictions. Together, these efforts draw a richer picture of social cognition in which predictive coding and feedback connections play significant roles. We further discuss how the notion of predicting coding is influencing how we think of autism spectrum disorder.

Neural mechanisms of costly helping in the general population and mirror-pain synesthetes.

It has been argued that experiencing the pain of others motivates helping. Here, we investigate the contribution of somatic feelings while witnessing the pain of others onto costly helping decisions, by contrasting the choices and brain activity of participants that report feeling somatic feelings (self-reported mirror-pain synesthetes) against those that do not. Participants in fMRI witnessed a confederate receiving pain stimulations whose intensity they could reduce by donating money. The pain intensity could be inferred either from the facial expressions of the confederate in pain (Face condition) or from the kinematics of the pain-receiving hand (Hand condition). Our results show that self-reported mirror-pain synesthetes increase their donation more steeply, as the intensity of the observed pain increases, and their somatosensory brain activity (SII and the adjacent IPL) was more tightly associated with donation in the Hand condition. For all participants, activation in insula, SII, TPJ, pSTS, amygdala and MCC correlated with the trial by trial donation made in the Face condition, while SI and MTG activation was correlated with the donation in the Hand condition. These results further inform us about the role of somatic feelings while witnessing the pain of others in situations of costly helping.

Cognitive control: exploring the causal role of the rTPJ in empathy for pain mediated by contextual information.

Empathy determines our emotional and social lives. Research has recognized the role of the right temporoparietal junction (rTPJ) in social cognition; however, there is less direct causal evidence for its involvement in empathic responses to pain, which is typically attributed to simulation mechanisms. Given the rTPJ's role in processing false beliefs and contextual information during social scenarios, we hypothesized that empathic responses to another person's pain depend on the rTPJ if participants are given information about people's intentions, engaging mentalizing mechanisms alongside simulative ones. Participants viewed videos of an actress freely showing or suppressing pain caused by an electric shock while receiving 6 Hz repetitive transcranial magnetic stimulation (rTMS) over the rTPJ or sham vertex stimulation. Active rTMS had no significant effect on participants' ratings depending on the pain expression, although participants rated the actress's pain as lower during rTPJ perturbation. In contrast, rTMS accelerated response times for providing ratings during pain suppression. We also found that participants perceived the actress's pain as more intense when they knew she would suppress it rather than show it. These results suggest an involvement of the rTPJ in attributing pain to others and provide new insights into people's behavior in judging others' pain when it is concealed.

A systematic review and multivariate meta-analysis of the physical and mental health benefits of touch interventions.

Receiving touch is of critical importance, as many studies have shown that touch promotes mental and physical well-being. We conducted a pre-registered (PROSPERO: CRD42022304281) systematic review and multilevel meta-analysis encompassing 137 studies in the meta-analysis and 75 additional studies in the systematic review (n = 12,966 individuals, search via Google Scholar, PubMed and Web of Science until 1 October 2022) to identify critical factors moderating touch intervention efficacy. Included studies always featured a touch versus no touch control intervention with diverse health outcomes as dependent variables. Risk of bias was assessed via small study, randomization, sequencing, performance and attrition bias. Touch interventions were especially effective in regulating cortisol levels (Hedges' g = 0.78, 95% confidence interval (CI) 0.24 to 1.31) and increasing weight (0.65, 95% CI 0.37 to 0.94) in newborns as well as in reducing pain (0.69, 95% CI 0.48 to 0.89), feelings of depression (0.59, 95% CI 0.40 to 0.78) and state (0.64, 95% CI 0.44 to 0.84) or trait anxiety (0.59, 95% CI 0.40 to 0.77) for adults. Comparing touch interventions involving objects or robots resulted in similar physical (0.56, 95% CI 0.24 to 0.88 versus 0.51, 95% CI 0.38 to 0.64) but lower mental health benefits (0.34, 95% CI 0.19 to 0.49 versus 0.58, 95% CI 0.43 to 0.73). Adult clinical cohorts profited more strongly in mental health domains compared with healthy individuals (0.63, 95% CI 0.46 to 0.80 versus 0.37, 95% CI 0.20 to 0.55). We found no difference in health benefits in adults when comparing touch applied by a familiar person or a health care professional (0.51, 95% CI 0.29 to 0.73 versus 0.50, 95% CI 0.38 to 0.61), but parental touch was more beneficial in newborns (0.69, 95% CI 0.50 to 0.88 versus 0.39, 95% CI 0.18 to 0.61). Small but significant small study bias and the impossibility to blind experimental conditions need to be considered. Leveraging factors that influence touch intervention efficacy will help maximize the benefits of future interventions and focus research in this field.

Nonlinear sound-sheet microscopy: imaging opaque organs at the capillary and cellular scale.

Light-sheet fluorescence microscopy has revolutionized biology by visualizing dynamic cellular processes in three dimensions. However, light scattering in thick tissue and photobleaching of fluorescent reporters limit this method to studying thin or translucent specimens. Here we show that non-diffractive ultrasonic beams used in conjunction with a cross-amplitude modulation sequence and nonlinear acoustic reporters enable fast and volumetric imaging of targeted biological functions. We report volumetric imaging of tumor gene expression at the cm 3 scale using genetically encoded gas vesicles, and localization microscopy of currently uncharted cerebral capillary networks using intravascular microbubble contrast agents. Nonlinear sound-sheet microscopy provides a ∼64x acceleration in imaging speed, ∼35x increase in imaged volume and ∼4x increase in classical imaging resolution compared to the state-of-the-art in biomolecular ultrasound.