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

AbstractEmpathy for pain involves the affective-motivational and sensory-discriminative pain network. The shared representations account postulates that sharing another’s 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 one’s 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 one’s 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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Another’s pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain

10.1101/2020.05.18.101238 ◽

2020 ◽

Author(s):

Helena Hartmann ◽

Markus Rütgen ◽

Federica Riva ◽

Claus Lamm

Keyword(s):

Brain Activity ◽

Critical Role ◽

Body Part ◽

Self Report ◽

List Type ◽

Placebo Analgesia ◽

Left Hand ◽

Right Hand ◽

Empathy For Pain ◽

The Right

AbstractThe shared representations account of empathy suggests that sharing other people’s 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.HighlightsInvestigated placebo modulation of somatosensory and affective components of painLocalized placebo analgesia effects for self-report and fMRI of first-hand painNo evidence for such effects in empathy for painSuggests that somatosensory sharing does not play a critical role in pain empathy

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A simulation-based approach to improve decoded neurofeedback performance

10.1101/450403 ◽

2018 ◽

Author(s):

Ethan Oblak ◽

James Sulzer ◽

Jarrod Lewis-Peacock

Keyword(s):

Real Time ◽

Brain Activity ◽

Processing Parameters ◽

Orientation Tuning ◽

Design Parameters ◽

Visual Orientation ◽

Brain Functions ◽

Simulation Based ◽

Using Data ◽

The Right

AbstractThe neural correlates of specific brain functions such as visual orientation tuning and individual finger movements can be revealed using multivoxel pattern analysis (MVPA) of fMRI data. Neurofeedback based on these distributed patterns of brain activity presents a unique ability for precise neuromodulation. Recent applications of this technique, known as decoded neurofeedback, have manipulated fear conditioning, visual perception, confidence judgements and facial preference. However, there has yet to be an empirical justification of the timing and data processing parameters of these experiments. Suboptimal parameter settings could impact the efficacy of neurofeedback learning and contribute to the ‘non-responder’ effect. The goal of this study was to investigate how design parameters of decoded neurofeedback experiments affect decoding accuracy and neurofeedback performance. Subjects participated in three fMRI sessions: two ‘finger localizer’ sessions to identify the fMRI patterns associated with each of the four fingers of the right hand, and one ‘finger finding’ neurofeedback session to assess neurofeedback performance. Using only the localizer data, we show that real-time decoding can be degraded by poor experiment timing or ROI selection. To set key parameters for the neurofeedback session, we used offline simulations of decoded neurofeedback using data from the localizer sessions to predict neurofeedback performance. We show that these predictions align with real neurofeedback performance at the group level and can also explain individual differences in neurofeedback success. Overall, this work demonstrates the usefulness of offline simulation to improve the success of real-time decoded neurofeedback experiments.

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Brain Activity During Predictable and Unpredictable Weight Changes When Lifting Objects

Journal of Neurophysiology ◽

10.1152/jn.00230.2004 ◽

2005 ◽

Vol 93 (3) ◽

pp. 1498-1509 ◽

Cited By ~ 48

Author(s):

Christina Schmitz ◽

Per Jenmalm ◽

H. Henrik Ehrsson ◽

Hans Forssberg

Keyword(s):

Brain Activity ◽

Inferior Frontal Gyrus ◽

Memory Systems ◽

Synaptic Activity ◽

Weight Changes ◽

Fmri Study ◽

Sensorimotor Memory ◽

Memory Representations ◽

The Right ◽

Fingertip Forces

When humans repetitively lift the same object, the fingertip forces are targeted to the weight of the object. The anticipatory programming of the forces depends on sensorimotor memory representations that provide information on the object weight. In the present study, we investigate the neural substrates of these sensorimotor memory systems by recording the neural activity during predictable or unpredictable changes in the weight of an object in a lifting task. An unpredictable change in weight leads to erroneous programming of the fingertip forces. This triggers corrective mechanisms and an update of the sensorimotor memories. In the present fMRI study, healthy right-handed subjects repetitively lifted an object between right index finger and thumb. In the constant condition, which served as a control, the weight of the object remained constant (either 230 or 830 g). The weight alternated between 230 and 830 g during the regular condition and was irregularly changed between the two weights during the irregular condition. When we contrasted regular minus constant and irregular minus constant, we found activations in the right inferior frontal gyrus pars opercularis (area 44), the left parietal operculum and the right supramarginal gyrus. Furthermore, irregular was associated with stronger activation in the right inferior frontal cortex as compared with regular. Taken together, these results suggest that the updating of sensorimotor memory representations and the corrective reactions that occur when we manipulate different objects correspond to changes in synaptic activity in these fronto-parietal circuits.

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Dissociating Neural Correlates of Action Monitoring and Metacognition of Agency

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00052 ◽

2011 ◽

Vol 23 (11) ◽

pp. 3620-3636 ◽

Cited By ~ 60

Author(s):

David B. Miele ◽

Tor D. Wager ◽

Jason P. Mitchell ◽

Janet Metcalfe

Keyword(s):

Brain Activity ◽

Dorsal Striatum ◽

Neural Correlates ◽

Action Monitoring ◽

Fmri Study ◽

Metacognitive Judgments ◽

The Right ◽

Reflective Processing ◽

Increased Activity ◽

The Brain

Judgments of agency refer to people's self-reflective assessments concerning their own control: their assessments of the extent to which they themselves are responsible for an action. These self-reflective metacognitive judgments can be distinguished from action monitoring, which involves the detection of the divergence (or lack of divergence) between observed states and expected states. Presumably, people form judgments of agency by metacognitively reflecting on the output of their action monitoring and then consciously inferring the extent to which they caused the action in question. Although a number of previous imaging studies have been directed at action monitoring, none have assessed judgments of agency as a potentially separate process. The present fMRI study used an agency paradigm that not only allowed us to examine the brain activity associated with action monitoring but that also enabled us to investigate those regions associated with metacognition of agency. Regarding action monitoring, we found that being “out of control” during the task (i.e., detection of a discrepancy between observed and expected states) was associated with increased brain activity in the right TPJ, whereas being “in control” was associated with increased activity in the pre-SMA, rostral cingulate zone, and dorsal striatum (regions linked to self-initiated action). In contrast, when participants made self-reflective metacognitive judgments about the extent of their own control (i.e., judgments of agency) compared with when they made judgments that were not about control (i.e., judgments of performance), increased activity was observed in the anterior PFC, a region associated with self-reflective processing. These results indicate that action monitoring is dissociable from people's conscious self-attributions of control.

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Processing of Targets in Smooth or Apparent Motion Along the Vertical in the Human Brain: An fMRI Study

Journal of Neurophysiology ◽

10.1152/jn.00892.2009 ◽

2010 ◽

Vol 103 (1) ◽

pp. 360-370 ◽

Cited By ~ 30

Author(s):

Vincenzo Maffei ◽

Emiliano Macaluso ◽

Iole Indovina ◽

Guy Orban ◽

Francesco Lacquaniti

Keyword(s):

Apparent Motion ◽

Visual Motion ◽

Brain Activity ◽

Activity Patterns ◽

Vertical Motion ◽

Constant Speed ◽

Lingual Gyrus ◽

Fmri Study ◽

Smooth Motion ◽

The Right

Neural substrates for processing constant speed visual motion have been extensively studied. Less is known about the brain activity patterns when the target speed changes continuously, for instance under the influence of gravity. Using functional MRI (fMRI), here we compared brain responses to accelerating/decelerating targets with the responses to constant speed targets. The target could move along the vertical under gravity (1 g), under reversed gravity (−1 g), or at constant speed (0 g). In the first experiment, subjects observed targets moving in smooth motion and responded to a GO signal delivered at a random time after target arrival. As expected, we found that the timing of the motor responses did not depend significantly on the specific motion law. Therefore brain activity in the contrast between different motion laws was not related to motor timing responses. Average BOLD signals were significantly greater for 1 g targets than either 0 g or −1 g targets in a distributed network including bilateral insulae, left lingual gyrus, and brain stem. Moreover, in these regions, the mean activity decreased monotonically from 1 g to 0 g and to −1 g. In the second experiment, subjects intercepted 1 g, 0 g, and −1 g targets either in smooth motion (RM) or in long-range apparent motion (LAM). We found that the sites in the right insula and left lingual gyrus, which were selectively engaged by 1 g targets in the first experiment, were also significantly more active during 1 g trials than during −1 g trials both in RM and LAM. The activity in 0 g trials was again intermediate between that in 1 g trials and that in −1 g trials. Therefore in these regions the global activity modulation with the law of vertical motion appears to hold for both RM and LAM. Instead, a region in the inferior parietal lobule showed a preference for visual gravitational motion only in LAM but not RM.

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Altered Spontaneous Brain Activity in Women During Menopause Transition and Its Association With Cognitive Function and Serum Estradiol Level

Frontiers in Endocrinology ◽

10.3389/fendo.2021.652512 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lemin He ◽

Wei Guo ◽

Jianfeng Qiu ◽

Xingwei An ◽

Weizhao Lu

Keyword(s):

Cognitive Function ◽

Brain Activity ◽

Premenopausal Women ◽

Spontaneous Brain Activity ◽

Brain Functions ◽

Perimenopausal Women ◽

Serum Hormone ◽

Menopause Transition ◽

Global Cognition ◽

The Right

ObjectiveSerum hormone deficiencies during menopause transition may affect spontaneous brain activity and global cognition. The purpose of this study was to explore the differences in spontaneous brain activity between premenopausal and perimenopausal women, and to investigate the associations between spontaneous brain activity, serum hormone levels and global cognition.MethodsThirty-two premenopausal women (47.75 ± 1.55 years) and twenty-five perimenopausal women (51.60 ± 1.63 years) underwent resting-state functional MRI (fMRI) scan. Clinical information including Mini-Mental State Examination (MMSE), levels of estradiol (E2), free testosterone, progesterone, prolactin, follicle-stimulating hormone and luteinizing hormone were measured. Regional homogeneity (ReHo) was used to evaluate spontaneous brain activity alterations between perimenopausal and premenopausal women. Correlation analysis was used to investigate the associations between brain functional alterations and clinical measures in perimenopausal group.ResultsThe results demonstrated increased ReHo value in the right lingual gyrus (LG) and decreased ReHo value in the right superior frontal gyrus (SFG) in perimenopausal women compared with premenopausal women. In perimenopausal group, ReHo of the right LG showed a negative correlation with level of E2 (r = -0.586, p = 0.002), ReHo of the right SFG showed a positive correlation with level of E2 (r = 0.470, p = 0.018) and MMSE (r = 0.614, p = 0.001).ConclusionsThe results demonstrated that women approaching menopause suffered from altered functions in brain regions related to cognitive function, working memory, the results also revealed a direct association between levels of E2 and brain functions in perimenopausal women.

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Oxytocin reduces interoceptive influences on empathy-for-pain in the anterior insula

10.1101/2021.10.22.465431 ◽

2021 ◽

Author(s):

Sophie Jacqueline Andree Betka ◽

Cassandra Gould Van Praag ◽

Charlotte Rae ◽

Gaby Pfeiffer ◽

Henrique Sequeira ◽

...

Keyword(s):

Linear Models ◽

Brain Activity ◽

Social Cues ◽

Anterior Cingulate ◽

Internal States ◽

Empathy For Pain ◽

Central Representation ◽

Psychiatric Conditions ◽

The Right ◽

Male Subjects

Empathy-for-pain states are underpinned by interoception, i.e the central representation of internal states. Cardiac signals occur in a phasic manner; baroreceptor discharges at systole communicate the heartbeats′ strength. These signals modulate pain and emotion processing. We tested whether these phasic interoceptive signals modulate empathy-for-pain. As oxytocin (OT) enhances empathy and modulates interoceptive signals′ precision, we also tested if OT administration impacts empathy-for-pain via interoceptive mechanisms. Male subjects (N=32) attended three sessions to perform psychometric tests and an fMRI empathy-for-pain task, after intranasal administration of OT or placebo (40IU). Pictures of hands in painful or non-painful context were presented at systole or diastole. Effects of drug, emotion and cardiac timing on behaviour and brain activity was tested using general and mixed-effects linear models. Across conditions, activation was observed within regions implicated in pain and empathy-for-pain, with insula activation greater in the right than left hemisphere. OT administration, compared to placebo, attenuated the reactivity of some regions, including anterior cingulate cortex, but presentation of stimuli at systole blocked the OT attenuating effect. Our data suggest that OT alters the processing of motivationally-salient social cues, interacting with interoceptive signals. Our findings may inform targeted use of OT in psychiatric conditions linked to aberrant interoceptive processing.

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Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2101273118 ◽

2021 ◽

Vol 118 (19) ◽

pp. e2101273118

Author(s):

Yiheng Tu ◽

Georgia Wilson ◽

Joan Camprodon ◽

Darin D. Dougherty ◽

Mark Vangel ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medical Practice ◽

Brain Activity ◽

Placebo Analgesia ◽

Double Blind ◽

Cathodal Tdcs ◽

Nocebo Effects ◽

The Right ◽

Manipulation Model ◽

Pain Regulation

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain’s descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.

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Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511269112 ◽

2015 ◽

Vol 112 (41) ◽

pp. E5638-E5646 ◽

Cited By ~ 91

Author(s):

Markus Rütgen ◽

Eva-Maria Seidel ◽

Giorgia Silani ◽

Igor Riečanský ◽

Allan Hummer ◽

...

Keyword(s):

Opioid Antagonist ◽

Neural Responses ◽

Placebo Analgesia ◽

Hand Pain ◽

Midcingulate Cortex ◽

Novel Approach ◽

Concomitant Reduction ◽

Empathy For Pain ◽

Neurotransmitter Activity ◽

Pain Experiences

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding “normalization” of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.

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Effects of a CACNA1C genotype on attention networks in healthy individuals

Psychological Medicine ◽

10.1017/s0033291710002217 ◽

2010 ◽

Vol 41 (7) ◽

pp. 1551-1561 ◽

Cited By ~ 49

Author(s):

M. Thimm ◽

T. Kircher ◽

T. Kellermann ◽

V. Markov ◽

S. Krach ◽

...

Keyword(s):

Executive Control ◽

Neural Activity ◽

Brain Activity ◽

Attention Deficits ◽

Neural Function ◽

Control Mechanisms ◽

Attention Networks ◽

Impaired Performance ◽

Fmri Study ◽

The Right

BackgroundRecent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder. In these disorders, attention deficits are among the main cognitive symptoms and have been related to altered neural activity in cerebral attention networks. The particular effect of CACNA1C on neural function, such as attention networks, remains to be elucidated.MethodThe current event-related functional magnetic resonance imaging (fMRI) study investigated the effect of the CACNA1C gene on brain activity in 80 subjects while performing a scanner-adapted version of the Attention Network Test (ANT). Three domains of attention were probed simultaneously: alerting, orienting and executive control of attention.ResultsRisk allele carriers showed impaired performance in alerting and orienting in addition to reduced neural activity in the right inferior parietal lobule [Brodmann area (BA) 40] during orienting and in the medial frontal gyrus (BA 8) during executive control of attention. These areas belong to networks that have been related to impaired orienting and executive control mechanisms in neuropsychiatric disorders.ConclusionsOur results suggest that CACNA1C plays a role in the development of specific attention deficits in psychiatric disorders by modulation of neural attention networks.

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