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Lamm, C.

Publications and source records attributed to Lamm, C..

35 records · Page 2Linked to original sources

Effective connectivity reveals distinctive patterns in response to others' genuine affective experience of disgust as compared to pain

Empathy is significantly influenced by the identification of others emotions. In a recent study, we have found increased activation in the anterior insular cortex (aIns) that could be attributed to affect sharing rather than perceptual saliency, when seeing another person genuinely experiencing pain as opposed to merely acting to be in pain. In that prior study, effective connectivity between aIns and the right supramarginal gyrus (rSMG) was revealed to track what another person really feels. In the present study, we used a similar paradigm to investigate the corresponding neural signatures in the domain of empathy for disgust - with participants seeing others genuinely sniffing unpleasant odors as compared to pretending to smell something disgusting. Consistent with the previous findings on pain, we found stronger activations in aIns associated with affect sharing for genuine disgust compared with pretended disgust. However, instead of rSMG we found engagement of the olfactory cortex. Using dynamic causal modeling (DCM), we estimated the neural dynamics of aIns and the olfactory cortex between the genuine and pretended conditions. This revealed an increased excitatory modulatory effect for genuine disgust compared to pretended disgust. For genuine disgust only, brain-to-behavior regression analyses highlighted a link between the observed modulatory effect and the perspective-taking empathic trait. Altogether, the current findings complement and expand our previous work, by showing that perceptual saliency alone does not explain responses in the insular cortex. Moreover, it reveals that different brain networks are implicated in a modality-specific way when sharing the affective experiences associated with pain vs. disgust.

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Similarities and differences of face and body perception in the dog (Canis familiaris) and human brain

Comparing the neural correlates of socio-cognitive skills across species provides insights into the evolution of the social brain and has revealed face- and body-sensitive regions in the primate temporal lobe. Although from a different lineage, dogs share convergent visuo-cognitive skills with humans and a temporal lobe which evolved independently in carnivores. We investigated the neural correlates of face and body perception in dogs (N = 15) and humans (N = 40) using functional MRI. Combining univariate and multivariate analysis approaches, we found functionally analogous occipito-temporal regions involved in the perception of animate entities and bodies in both species, while only humans had regions specialized for face perception. Though unpredicted, we also observed neural representations of faces compared to inanimate objects, and dog compared to human bodies in dog olfactory regions. These findings shed light on the evolutionary foundations of human and dog social cognition and the predominant role of the temporal lobe.

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Enhanced negative response to stress following morphine administration increases wanting of social reward

Animal research suggests a central role of the -opioid receptor (MOR) system in regulating affiliative behaviors and in mediating the stress-buffering function of social contact. However, the neurochemistry of stress-related social contact seeking in humans is still poorly understood. In a randomized, double-blind, between-subject design, healthy female volunteers (N = 80) received either 10 mg of the -opioid agonist morphine sulfate, or a placebo. Following a standardized psychosocial stress induction, participants engaged in a social reward task, in which the motivation to obtain skin-to-skin social touch and the hedonic reactions elicited by such touch were assessed. Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure. Notably, this altered HPA axis responsivity was associated with increased negative affect in response to psychosocial stress, and with enhanced subjective wanting of highly rewarding social contact. These findings provide novel evidence on the effect of exogenous opioids administration on the reactions to psychosocial stress and point to a state-dependent regulation of social motivation.

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In amygdala we trust: different contributions of the basolateral and central amygdala in learning whom to trust

Human societies are built on cooperation and mutual trust, but not everybody is trustworthy. Research on rodents suggests an essential role of the basolateral amygdala (BLA) in learning from social experiences (Hernandez-Lallement J et al., 2016), which was also confirmed in human subjects with selective bilateral BLA damage as they failed to adapt their trust behavior towards trustworthy vs. untrustworthy interaction partners (Rosenberger LA et al., 2019). However, neuroimaging in neurotypical populations did not consistently report involvement of the amygdala in trust behavior. This might be explained by the difficulty of differentiating between amygdalas structurally and functionally different subnuclei, i.e., the BLA and central amygdala (CeA), which have even antagonistic features particularly in trust behavior (van Honk J et al., 2013). Here, we used fMRI of the amygdala subnuclei of neurotypical adults (n=31f/31m) engaging in the repeated trust game. Our data show that both the BLA and the CeA play a role and indeed differentially: While the BLA was most active when obtaining feedback on whether invested trust had been reciprocated or not, the CeA was most active when subjects were preparing their next trust decision. In the latter phase, improved learning was associated with higher activation differences in response to untrustworthy vs. trustworthy trustees, in both BLA and CeA. Our data not only translate to rodent models and support our earlier findings in BLA-damaged subjects, but also show the specific contributions of other brain structures in the amygdala-centered network in learning whom to trust, and better not to trust. SIGNIFICANCE STATEMENTIn this fMRI study, the central amygdala was found active during trust behavior planning, while the basolateral amygdala was active during outcome evaluation. When planning trust behavior, central and basolateral amygdala activation differences between the players was related to whether participants learned to differentiate the players trustworthiness. Nucleus accumbens tracked whether trust was reciprocated but was not related to learning. This suggests learning whom to trust is not related to reward processing in the nucleus accumbens but rather to engagement of the basolateral amygdala. This study overcomes major empirical gaps between animal models and human neuroimaging and shows how different amygdala subnuclei and connected areas orchestrate learning to form different subjective trustworthiness beliefs about others and guide trust choice behavior.

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Negative Urgency as a Risk Factor for Hazardous Alcohol Use: Dual Influences of Cognitive Control and Reinforcement Processing

Negative Urgency (NU) is a prominent risk factor for hazardous alcohol use. While research has helped elucidate how NU relates to neurobiological functioning with respect to alcohol use, no known work has contextualized such functioning within existing neurobiological theories in addiction. Therefore, we elucidated mechanisms contributing to the NU-hazardous alcohol use relationship by combining NU theories with neurobiological dual models of addiction, which posit addiction is related to cognitive control and reinforcement processing. Fifty-five undergraduates self-reported NU and hazardous alcohol use. We recorded EEG while participants performed a reinforced flanker task. We measured cognitive control using N2 activation time-locked to the incongruent flanker stimulus, and we measured reinforcement processing using the feedback-related negativity (FRN) time-locked to better-than-expected negative reinforcement feedback. We modeled hazardous drinking using hierarchical regression, with NU, N2, and FRN plus their interactions as predictors. The regression model significantly predicted hazardous alcohol use, and the three-way interaction (NUxN2xFRN) significantly improved model fit. In the context of inefficient processing (i.e., larger N2s and FRNs), NU demonstrated a strong relationship with hazardous alcohol use. In the context of efficient processing (i.e., smaller N2s and FRNs), NU was unrelated to hazardous alcohol use. This analysis provides preliminary evidence that brain mechanisms of cognitive control and reinforcement processing influence the relationship between NU and hazardous alcohol use, and confirms a specific influence of negative reinforcement processing. Future clinical research could leverage these neurobiological moderators for substance misuse treatment.

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Neural dynamics between anterior insular cortex and right supramarginal gyrus dissociate genuine affect sharing from automatic responses to pretended pain

Empathy for pain engages both shared affective responses and self-other distinction. In this study, we addressed the highly debated question of whether neural responses previously linked to affect sharing could result from the perception of salient affective displays. Moreover, we investigated how affect sharing and self-other distinction interact to determine our response to a pain that is either perceived as genuine or pretended (while in fact both were acted for reasons of experimental control). We found stronger activations in regions associated with affect sharing (anterior insula, aIns, and anterior mid-cingulate cortex, aMCC) as well as with affective self-other distinction (right supramarginal gyrus, rSMG), in participants watching video clips of genuine vs. pretended facial expressions of pain. Using dynamic causal modeling (DCM), we then assessed the neural dynamics between the right aIns and rSMG in these two conditions. This revealed a reduced inhibitory effect on the aIns to rSMG connection for genuine compared to pretended pain. For genuine pain only, brain-to-behavior regression analyses highlighted a linkage between this inhibitory effect on the one hand, and pain ratings as well as empathic traits on the other. These findings imply that if the pain of others is genuine and thus calls for an appropriate empathic response, neural responses in the aIns indeed seem related to affect sharing and self-other distinction is engaged to avoid empathic over-arousal. In contrast, if others merely pretend to be in pain, the perceptual salience of their painful expression results in neural responses that are down-regulated to avoid inappropriate affect sharing and social support.

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Effects of non-invasive brain stimulation on visual perspective taking: A meta-analytic study

Visual perspective taking (VPT) is a critical ability required by complex social interaction. Non-invasive brain stimulation (NIBS) has been increasingly used to examine the causal relationship between brain activity and VPT, yet with heterogeneous results. In the current study, we conducted two meta-analyses to examine the effects of NIBS of the right temporoparietal junction (rTPJ) or dorsomedial prefrontal cortex (dmPFC) on VPT, respectively. We performed a comprehensive literature search to identify qualified studies, and computed the standardized effect size (ES) for each combination of VPT level (Level-1: visibility judgment; Level-2: mental rotation) and perspective (self and other). Thirteen studies (rTPJ: 12 studies, 23 ESs; dmPFC: 4 studies, 14 ESs) were included in the meta-analyses. Random-effects models were used to generate the overall effects. Subgroup analyses for distinct VPT conditions were also performed. We found that rTPJ stimulation significantly improved participants visibility judgment from the allocentric perspective, whereas its effects on other VPT conditions are negligible. Stimulation of dmPFC appeared to influence Level-1 performance from the egocentric perspective, although it was only based on a small number of studies. Notably, contrary to some theoretical models, we did not find strong evidence that these regions are involved in Level-2 VPT with a higher requirement of mental rotation. These findings not only advanced our understanding of the causal roles of the rTPJ and dmPFC in VPT, but also revealed the efficacy of NIBS on VPT is relatively small. Researchers should also be cautious about the potential publication bias and selective reporting.

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Placebo analgesia does not reduce empathy for naturalistic depictions of others' pain in a somatosensory specific way

Empathy for pain involves the affective-motivational and sensory-discriminative pain network. The shared representations account postulates that sharing anothers pain recruits underlying brain functions also engaged during first-hand pain. Critically, causal evidence for this has only been shown for affective pain processing, while the specific contribution of ones own somatosensory system to empathy remains controversial. Experimental paradigms used in previous studies did not a) direct attention towards a specific body part or b) employed naturalistic depictions of others pain, which could explain the absence of somatosensory effects. In this preregistered fMRI study, we thus aimed to test whether a causal manipulation of first-hand pain affects processing of empathy in a somatotopically- matched manner. Forty-five participants underwent a placebo analgesia induction in the right hand and observed pictures of right vs. left hands in pain. We found neither behavioral nor neural evidence for laterality-specific modulation of empathy for pain. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others hands in pain corresponding to ones own placebo hand. These results refine our knowledge regarding the mechanisms underlying empathy for pain by specifying the influence of first-hand pain on empathic responding.

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Beyond sharing unpleasant affect - evidence for pain-specific opioidergic modulation of empathy for pain

The neural mechanisms underpinning empathy for pain are still a matter of debate. One of the major questions is whether empathy-related pain responses indicate domain-general vs. pain-specific affective responses. Using fMRI and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them to the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiate the role of shared representations in empathy.

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Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain

The shared representations account of empathy suggests that sharing other peoples emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models. HighlightsO_LIInvestigated placebo modulation of somatosensory and affective components of pain C_LIO_LILocalized placebo analgesia effects for self-report and fMRI of first-hand pain C_LIO_LINo evidence for such effects in empathy for pain C_LIO_LISuggests that somatosensory sharing does not play a critical role in pain empathy C_LI

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Durable memories and efficient neural coding through mnemonic training using the method of loci

Mnemonic techniques, such as the method of loci, can powerfully boost memory. Here, we compared memory athletes ranked among the worlds top 50 in memory sports to mnemonics-naive controls. In a second study, participants completed a six-weeks memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. fMRI during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after four months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings are the first to demonstrate that mnemonic training boosts durable memory formation via decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.

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Tailored haemodynamic response function increases detection power of fMRI in awake dogs (Canis familiaris)

Functional magnetic resonance imaging (fMRI) of awake and unrestrained dogs (Canis familiaris) has been established as a novel opportunity for comparative neuroimaging, promising important insights into the evolutionary roots of human brain function and cognition. However, data processing and analysis pipelines are often derivatives of methodological standards developed for human neuroimaging, which may be problematic due to profound neurophysiological and anatomical differences between humans and dogs. Here, we explore whether dog fMRI studies would benefit from a tailored dog haemodynamic response function (HRF). In two independent experiments, dogs were presented with different visual stimuli. BOLD signal changes in the visual cortex during these experiments were used for (a) the identification and estimation of a tailored dog HRF, and (b) the independent validation of the resulting dog HRF estimate. Time course analyses revealed that the BOLD signal in the primary visual cortex peaks significantly earlier in dogs compared to humans, while being comparable in shape. Deriving a tailored dog HRF significantly improved the model fit in both experiments, compared to the canonical HRF used in human fMRI. Using the dog HRF yielded significantly increased activation during visual stimulation, extending from the occipital lobe, to the caudal parietal cortex, the bilateral temporal cortex, and into bilateral hippocampal and thalamic regions. In sum, our findings provide robust evidence for an earlier onset of the dog HRF in a visual stimulation paradigm, and suggest that using such an HRF will be important to increase fMRI detection power in canine neuroimaging. By providing the parameters of the tailored dog HRF and related code, we encourage and enable other researchers to validate whether our findings generalize to other sensory modalities and experimental paradigms. HighlightsO_LIDog fMRI typically uses human HRF, but underlying neurophysiology might differ C_LIO_LIV1 BOLD signal peaked earlier in dogs than predicted by the human HRF C_LIO_LITailored dog HRF improved model fit when tested with independent data C_LIO_LIWhole-brain comparisons confirmed increased detection power for tailored dog HRF C_LIO_LIDog fMRI will benefit from increased detection power of tailored HRF C_LI

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A causal role for estradiol in human reinforcement learning

The sex hormone estrogen is hypothesized to play a key role in human cognition via its interactions with the dopaminergic system. Work in rodents has shown that estrogens most potent form, estradiol, impacts striatal dopamine functioning predominately via increased D1-receptor signalling, while human work has suggested that high estradiol levels are associated with altered reward sensitivity. Here, we addressed two fundamental questions: 1) whether estradiol causally alters reward sensitivity in men, and 2) whether this effect of estradiol is moderated by individual variation in polymorphisms of dopaminergic genes. To test this, we performed a double-blind placebo-controlled administration study in which hundred men received either a single dose of estradiol (2 mg) or placebo. We found that estradiol administration increased reward sensitivity, which was moderated by baseline dopamine. This was observed in choice behaviour and increased learning rates. These results confirm a causal role of estradiol in reinforcement learning in men that is moderated by the striatal dopaminergic pathway.

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Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain

Empathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between fist-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal MPFC was increased the more dissimilar the other individual was perceived. Moreover, hippocampal connectivity with regions engaged in first-hand pain was also increased during pain empathy, during which hippocampal coupling with the fusiform gyrus positively scaled with self-report measures of individual perspective taking skills. These findings highlight that shared representations and interactions within a hippocampal-neocortical network support pain empathy. This potentially reflects memory-based mental simulation processes, which seem partially modulated by personality traits and the perceived similarity of the other individual in pain.

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Neuro-Computational Foundations of Moral Preferences

Moral preferences pervade many aspects of our lives, dictating how we ought to behave, whom we can marry, and even what we eat. Despite their relevance, one fundamental question remains unanswered: Where do individual moral preferences come from? It is often thought that all types of preferences reflect properties of domain-general neural decision mechanisms that employ a common \"neural currency\" to value choice options in many different contexts. This assumption, however, appears at odds with the observation that many humans consider it intuitively wrong to employ the same scale to compare moral value (e.g., of a human life) with material value (e.g., of money). In this paper, we directly challenge the common-currency hypothesis by comparing the neural mechanisms that represent moral and financial subjective values. In a study combining fMRI with a novel behavioral paradigm, we identify neural representations of the subjective values of human lives or financial payoffs by means of structurally identical computational models. Correlating isomorphic model variables from both domains with brain activity reveals specific patterns of neural activity that selectively represent values in the moral (in the rTPJ) or financial (in the vmPFC) domain. Thus, our findings show that human lives and money are valued in distinct neural currencies, supporting theoretical proposals that human moral behavior is guided by processes that are distinct from those underlying behavior driven by personal material benefit.

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Age-related changes in human emotional egocentricity: evidence from multi-level neuroimaging

Emotional egocentric bias (EEB) occurs when, due to a partial failure in self-other distinction, empathy for anothers emotions is influenced by our own emotional state. Recent studies have demonstrated that this bias is higher in children, adolescents and older adults than in young adults. In the latter, overcoming emotional egocentrism has been associated with significant activity in the right supramarginal gyrus (rSMG), as well as increased connectivity between rSGM and somatosensory and visual cortices. Investigations on the neural correlates of EEB in adolescents and older adults are missing. We filled this gap, by asking female participants from three different age groups (adolescents, young adults and older adults, N=92) to perform a well-validated EEB task (Silani et al., 2013) in an MRI scanner. A multi-level analysis approach of MRI data including functional segregation, effective connectivity and structural analyses was adopted. Results revealed higher EEB in older compared to young adults and a comparable EEB in adolescents and young adults. Age-related differences in EEB were associated with differences in task-related rSMG connectivity with somatosensory cortices, especially with S2, which acted as a partial mediator between age and EEB. These findings provide further evidence for the crucial role of the rSMG in self-other distinction in the emotional domain, and suggest that the age-related decline in overcoming EEB is best explained by changes in rSMG connectivity rather than decreased regional activity in that area. This advocates a more systematic investigation of task-related connectivity in studies on aging and life-span development of social-cognitive phenomena.\n\nSignificance StatementEmpathy comprises both the ability to identify and share anothers emotional state, and the ability to disentangle ones own from the others emotional state. When self- and other-related emotions are conflicting, empathy might be negatively influenced by egocentric tendencies. This phenomenon is referred to as emotional egocentric bias (EEB), with previous research showing that its extent changes across the life-span. Here, we provide evidence that age-related differences in EEB are mainly associated with age-related changes in rSMG effective connectivity, and in particular that higher EEB in older adults is associated to lower rSMG effective connectivity with somatosensory cortices. These findings suggest the importance, particularly in aging, of intact functional connectivity for optimal socio-cognitive functioning.

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Placebo-induced pain reduction is associated with inverse network coupling at rest

Placebos can reduce pain by inducing beliefs in the effectiveness of an actually inert treatment. Such top-down effects on pain typically engage lateral and medial prefrontal regions, the insula, somatosensory cortex, as well as the thalamus and brainstem during pain anticipation or perception. Considering the level of large-scale brain networks, these regions spatially align with fronto-parietal/executive control, salience, and sensory-motor networks, but it is unclear if and how placebos alter interactions between them during rest. Here, we investigated how placebo analgesia affected intrinsic network coupling. Ninety-nine human participants were randomly assigned to a placebo or control group and underwent resting-state fMRI after pain processing. Results revealed inverse coupling between sensory-motor and salience-like networks in placebo but not control participants. Specifically, networks were centered on the bilateral somatosensory cortex, as well as on the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, but was unrelated to expectations of medication effectiveness in the placebo group. Altogether, these findings provide initial evidence that placebo analgesia affects the intrinsic communication between large-scale brain networks, even in the absence of pain. We suggest a model where placebo analgesia increases activation within a descending pain-modulatory network, segregating it from somatosensory regions that might code for painful experiences.\n\nHighlightsO_LIPlacebo analgesia affects resting-state connectivity between networks.\nC_LIO_LISalience-related and somatosensory regions are negatively coupled at rest.\nC_LIO_LIThis coupling is negative following placebo, but not in control participants.\nC_LIO_LIMore negative between-network coupling is related to lower pain intensity.\nC_LI

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