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

May combine two claims.

There were nonsignificant effects of Group and Group × Condition on physical pain ratings.

“and nonsignificant effects of Group (F(1,30) = 0.66; P = 0.422) and Group × Condition (F(1,30) = 0.075; P = 0.787, see Table 1) on the pain ratings.”

May combine two claims.

During the SP task, there was substantial heterogeneity in individual activation parameters within the ASD group, and interindividual differences in AIC activation were larger in ASD than HC (ASD SD=0.19, HC SD=0.13).

“The inspection of individual activation parameters showed substantial heterogeneity during the SP task within the ASD group and the interindividual differences of the AIC activation during SP were somewhat larger in individuals with ASD compared with healthy controls (ASD: SD = 0.19, HC: SD = 0.13, Fig. 2c).”

May combine two claims.

There were no significant effects of Group or Group × Condition interaction on pupil diameter during physical pain.

“and no significant effects of Group (F(1,20) = 0.68; P = 0.797) or Group × Condition interaction (F(1,20) = 1.21; P = 0.284).”

May combine two claims.

During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the AIC and ACC.

“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).”

May combine two claims.

The neural response during vicarious SP is related to the ADOS-SA, which substantiates the finding for reduced neural responses in more complex social situations.

“In this line, we observe the neural response during vicarious SP to be related to the ADOS‐SA which additionally substantiates the finding for reduced neural responses in more complex social situations.”

May combine two claims.

The neural response of the AIC and ACC as well as the pupil response of the ASD group were very similar compared to HC during vicarious physical pain.

“The neural response of the AIC and ACC as well as the pupil response of the ASD group were very similar compared to HC, thereby replicating recent findings on vicarious physical pain in ASD [Bird et al., 2010; Hadjikhani et al., 2014].”

• cites Bird et al., 2010Not checked yet

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• cites Hadjikhani et al., 2014Not checked yet

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Classified as probably not a substantial claim.

The deficient embodied representation has been attributed to malfunctions of the interoceptive cortex, a network comprising the AIC and ACC.

“The deficient embodied representation has been attributed to malfunctions of the interoceptive cortex [Craig, 2002, 2003], a network comprising the anterior insula cortex (AIC) and the anterior cingulate cortex (ACC) [Bird et al., 2010; Silani et al., 2008].”

• cites Craig, 2002, 2003Not checked yet

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• cites Bird et al., 2010Not checked yet

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• cites Silani et al., 2008Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable).

Embodied representations of emotions are thought to underlie and motivate socially competent behavior.

“Such embodied representations of emotions are thought to underlie and motivate socially competent behavior [Eisenberg and Miller, 1987; Hein et al., 2010].”

• cites Eisenberg and Miller, 1987Not checked yet

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• cites Hein et al., 2010Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

A frequent explanation for this impairment is based on the patients' often described deficit in embodying another's affective states.

“A frequent explanation for this impairment is based on the patients' often described deficit in embodying another's affective states [Gallese et al., 2013; Hill et al., 2004].”

• cites Gallese et al., 2013Not checked yet

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• cites Hill et al., 2004Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

The AIC provides a salient representation of one's own bodily states and has been suggested to be a correlate of one's conscious experience of emotion.

“This network, and specifically the AIC, provides a salient representation of one's own bodily states and has been suggested to be a correlate of one's conscious experience of emotion [Gu et al., 2013].”

• cites Gu et al., 2013Not checked yet

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Classified as probably not a substantial claim.

The representation of another's affect is reached through the embodied simulation of our own states.

“The observation that the same regions are activated while witnessing the affect of other individuals led to the idea that the representation of another's affect is reached through the embodied simulation of our own states [Gallese and Sinigaglia, 2011; Keysers and Gazzola, 2009].”

• cites Gallese and Sinigaglia, 2011Not checked yet

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• cites Keysers and Gazzola, 2009Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

This reduced capacity predominantly alters experience and behavior within complex social situations.

“This affects many aspects of life, but predominantly alters experience and behavior within complex social situations [American Psychiatric Association, 2013; Klin et al., 2007].”

• cites American Psychiatric Association, 2013Not checked yet

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• cites Klin et al., 2007Not checked yet

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Classified as probably not a substantial claim.

Autism spectrum disorder (ASD) is characterized by substantial social deficits.

“Autism spectrum disorder (ASD) is characterized by substantial social deficits.”

• cites Levy et al., 2009Not checked yet

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• cites Lombardo et al., 2007, 2010Not checked yet

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Classified as probably not a substantial claim.

One of the core symptoms in high-functioning individuals with ASD is reduced capacity to intuitively represent their own and others' mental states.

“One of the core symptoms in high‐functioning individuals with autism spectrum disorder (ASD) is their reduced capacity to intuitively represent their own and others’ mental states [Levy et al., 2009; Lombardo et al., 2007, 2010].”

• cites Levy et al., 2009Not checked yet

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• cites Lombardo et al., 2007, 2010Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

Emotional resonance can occur for others' primary emotions such as physical pain or disgust, as well as for more complex social emotions such as rejection and embarrassment.

“Emotional resonance can occur for others’ primary emotions such as physical pain [Singer et al., 2004] or disgust [Wicker et al., 2003], as well as for more complex social emotions such as rejection and embarrassment [Beeney et al., 2011; Krach et al., 2011; Paulus et al., 2014].”

• cites Singer et al., 2004Not checked yet

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• cites Wicker et al., 2003Not checked yet

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• cites Beeney et al., 2011Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

Using this strategy, patients with ASD learn to navigate the complex social world being less dependent on social intuition.

“Using this strategy, patients with ASD learn to navigate the complex social world being less dependent on social intuition.”

Classified as probably not a substantial claim.

Pupil dilation is considered to be a measure of autonomic arousal which provides an additional and directly observable quantitative measure of the temporal pattern of brain reactivity to emotional stimuli.

“Pupil dilation is considered to be a measure of autonomic arousal which provides an additional and directly observable quantitative measure of the temporal pattern of brain reactivity to emotional stimuli [Silk et al., 2007].”

• cites Silk et al., 2007Not checked yet

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Classified as probably not a substantial claim.

Previous results stress the AIC and the ACC as key regions in processing physical pain and social pain.

“Previous results stress the AIC and the ACC as key regions in processing PP and SP.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The hippocampus including the parahippocampal gyrus is a key region for memory processes.

“We therefore generated an anatomical mask of the hippocampus including the parahippocampal gyrus — a key region for memory processes [Squire et al., 2004] — as defined by the anatomical labeling atlas with a dilation factor of one [Tzourio‐Mazoyer et al., 2002].”

• cites Squire et al., 2004Not checked yet

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Probably not a substantial claim: may not pass S4 (based).

While witnessing others' physical pain, the individual's own body provides sufficient input to build an adequate model of another's affect.

“Basically, while witnessing others’ PP, the individual's own body provides sufficient input to build an adequate model of another's affect.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The concept of social pain has been conceptualized much broader, also including negative affective states such as shame, guilt, or embarrassment because they provide signs that one might not live up to others' standards.

“However, the concept of social pain has been conceptualized much broader, also including negative affective states such as shame, guilt, or embarrassment because they provide signs that one might not live up to others’ standards [Macdonald and Leary, 2005].”

• cites Macdonald and Leary, 2005Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable).

Social norms, conventions, and etiquettes are culturally learned connections of certain behaviors with certain social occasions.

“Similar to tasks that require different elements to be remembered as a pair, such as a name and a face [Squire et al., 2004], social norms, conventions, and etiquettes are culturally learned connections of certain behaviors with certain social occasions (e.g., wearing a black suit at a funeral).”

• cites Squire et al., 2004Not checked yet

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Classified as probably not a substantial claim.

Vicarious responses for social pain result in cortical activation comparable to those associated with vicarious physical pain.

“Vicarious responses for SP result in cortical activation comparable to those associated with vicarious PP [Immordino‐Yang et al., 2009; Krach et al., 2011; Masten et al., 2011], and are coupled with increased autonomic activation [Müller‐Pinzler et al., 2012].”

• cites Immordino‐Yang et al., 2009Not checked yet

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• cites Krach et al., 2011Not checked yet

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• cites Masten et al., 2011Not checked yet

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Classified as probably not a substantial claim.

Embarrassment on behalf of others' mishaps constitutes a form of vicarious social pain.

“Embarrassment on behalf of others’ mishaps (e.g., observing a waiter in a fully occupied restaurant stumbling and dropping dishes to the floor) constitutes a form of vicarious social pain [Krach et al., 2011; Müller‐Pinzler et al., 2012; Paulus et al., 2013b, 2014]1.”

• cites Krach et al., 2011Not checked yet

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• cites Müller‐Pinzler et al., 2012Not checked yet

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• cites Paulus et al., 2013b, 2014Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

Although the emotion of embarrassment is conceptually different from the experience of social exclusion, both share the underlying threat to one's social integrity which justifies integrating embarrassment in the broader construct of social pain.

“Although the emotion of embarrassment is conceptually different from the experience of social exclusion, both share the underlying threat to one's social integrity which justifies integrating embarrassment in the broader construct of social pain.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The experience of vicarious social pain - particularly embarrassment - is thought to signal threats to another's social integrity.

“Likewise, the experience of vicarious social pain (henceforth SP) — and particularly embarrassment — is thought to serve a similar function, thereby signaling threats to another's social integrity [Macdonald and Leary, 2005; Krach et al., 2011; Paulus et al., 2014].”

• cites Macdonald and Leary, 2005Not checked yet

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• cites Krach et al., 2011Not checked yet

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• cites Paulus et al., 2014Not checked yet

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Classified as probably not a substantial claim.

A longstanding theory in autism research suggests that from the time of their early childhood onwards, patients with ASD try to compensate for their lack of social intuition by adhering to learned social rules and conventions - often in an inflexible or stereotyped manner.

“A longstanding theory in autism research suggests that from the time of their early childhood onwards, patients with ASD try to compensate for their lack of social intuition by adhering to learned social rules and conventions – often in an inflexible or stereotyped manner [Baron‐Cohen et al., 2003; Klin et al., 2003].”

• cites Baron‐Cohen et al., 2003Not checked yet

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• cites Klin et al., 2003Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Vicarious responses for social pain are coupled with increased autonomic activation.

“Vicarious responses for SP result in cortical activation comparable to those associated with vicarious PP [Immordino‐Yang et al., 2009; Krach et al., 2011; Masten et al., 2011], and are coupled with increased autonomic activation [Müller‐Pinzler et al., 2012].”

• cites Müller‐Pinzler et al., 2012Not checked yet

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Classified as probably not a substantial claim.

Neuropsychological data, imaging and lesion studies show that the hippocampus is highly implicated in memory formation.

“Neuropsychological data, imaging and lesion studies show that the hippocampus is highly implicated in memory formation [Squire, 1992; Squire and Zola‐Morgan, 1991].”

• cites Squire, 1992Not checked yet

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• cites Squire and Zola‐Morgan, 1991Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The negative affect induced by witnessing another person's physical pain is thought to provide strong signals for the injuries of another's bodily integrity.

“The negative affect induced by witnessing another person's PP is thought to provide strong signals for the injuries of another's bodily integrity [Singer et al., 2004].”

• cites Singer et al., 2004Not checked yet

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May combine two claims.

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.

“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.”

May combine two claims.

ASD individuals did not base their self-report on the embodied representations of affect in the ACC/AIC network, but instead showed a stronger association with the hippocampus.

“In contrast, ASD individuals did not base their self‐report on the embodied representations of affect in this network, but instead showed a stronger association with the hippocampus”

Classified as probably not a substantial claim. May combine two claims.

Healthy controls were matched for sex, age, and verbal IQ.

“Healthy controls (HC; N = 16) were matched for sex, age (ASD: M = 21.5 years; HC: M = 24.3 years; t(30) = 2.68; P = 0.012), and verbal IQ (ASD: M = 117.4; HC: M = 113.3; t(28) = 0.93; P = 0.368) using the Wechsler Adult Intelligence Scale [Tewes, 1991] (see Table 1).”

May combine two claims.

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.

“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.”

May combine two claims.

Persons with ASD use an alternative route to obtain the same behavior, and this provides the first evidence for differences in the underlying neurobiological mechanisms that link neural activation with behavior.

“Here, we show that persons with ASD use an alternative route to obtain the same behavior and we provide the first evidence for differences in the underlying neurobiological mechanisms that link neural activation with behavior.”

May combine two claims.

Group differences in head motion were examined and MANOVAs revealed no significant differences in subject's head motion between groups both for the averages and the variances.

“The four MANOVAs revealed no significant differences in subject's head motion between groups both for the averages (SP: F(6,25) = 1.36, P = 0.269; PP: F(6,25) = 1.07, P = 0.407) and the variances (SP: F(6,25) = 2.26, P = 0.070; PP: F(6,25) = 2.01, P = 0.102).”

Classified as probably not a substantial claim.

Valid pupil measurements were available for eleven ASD patients and eleven healthy controls.

“Valid pupil measurements were available for eleven ASD patients and eleven healthy controls (see Table 1).”

Classified as probably not a substantial claim. May combine two claims.

The AIC and ACC ROIs for physical pain were defined in an independent sample contrasting PP-PN, and the left AIC and ACC during social pain were derived from another independent sample with the respective contrast SP-SN.

“First, for PP, the bilateral AIC and ACC were defined in an independent sample contrasting PP‐PN [Paulus et al., 2015], and second, the left AIC and ACC during SP were derived from another independent sample with the respective contrast SP‐SN [Krach et al., 2011]”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study was approved by the local ethics committee and written informed consent was obtained from all participants.

“The study was approved by the local ethics committee and written informed consent was obtained from all participants involved in the study.”

Classified as probably not a substantial claim.

All results were family-wise error (FWE)-corrected for multiple comparisons either in whole-brain or ROI analyses using Gaussian-random field theory as implemented in SPM8.

“All results were family‐wise error (FWE)‐corrected for multiple comparisons either in whole‐brain or regions of interest (ROI) analyses using Gaussian‐random field theory as implemented in SPM8.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Social pain and social neutral stimuli did not differ regarding their luminance (t(48)=1.54, P=0.130).

“SP and SN stimuli did not differ regarding their luminance (t(48) = 1.54, P = 0.130).”

Classified as probably not a substantial claim. May combine two claims.

Physical pain and physical neutral stimuli were matched in number and for semantic content and luminance (t(27)=0.26, P=0.790).

“PP and PN were matched in number and for semantic content and luminance (t(27) = 0.26, P = 0.790).”

May combine two claims.

The lack of reliance on the interoceptive route in ASD manifests in diminished embodied affect as represented by reduced activation of the ACC and AIC as well as by the pupillary responses.

“The lack of reliance on the interoceptive route in ASD also manifests in diminished embodied affect as represented by reduced activation of the ACC and AIC as well as by the pupillary responses.”

Classified as probably not a substantial claim. May combine two claims.

Patients had a confirmed ICD-10 diagnosis of autism, Asperger syndrome, or atypical autism and underwent standardized diagnostic procedures with ADOS, WISC, and ADI-R.

“Patients (N = 16) were older than 18 years, male, and had a verbal IQ > 85; matched the DSM IV criteria for ASD; had a confirmed ICD‐10 diagnosis of autism (n = 1), Asperger syndrome (n = 14), or atypical autism (n = 1); had undergone standardized diagnostic procedures with either Module 3 or Module 4 of the Autism Diagnostic Observation Schedule (ADOS) [Lord et al., 2000, 2012; Rühl et al., 2004,”

May combine two claims.

Other factors such as the complexity of the situation and motivational aspects might impact the vicarious response.

“Instead, other factors such as the complexity of the situation [Paulus et al., 2013b] and motivational aspects [Chevallier et al., 2012] might impact the vicarious response.”

• cites Paulus et al., 2013bNot checked yet

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• cites Chevallier et al., 2012Not checked yet

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May combine two claims.

Activation within the AIC was inversely related to autism symptom severity in the domain of social affect, suggesting a central role of embodiment of others' affect for the emotional and social impairments in ASD.

“The activation within the AIC was thereby inversely related to autism symptom severity in the domain of social affect, suggesting a central role of embodiment of others' affect for the emotional and social impairments in ASD.”

May combine two claims.

This suggests the absence of domain-general disturbances in embodying affect in ASD, but points to a gradient regarding the complexity of social situations.

“This suggests the absence of domain‐general disturbances in embodying affect in ASD, but points to a gradient regarding the complexity of social situations.”

Probably not a substantial claim: may not pass S2 (checkable).

The present findings of impaired embodiment of others' affective states might have implications for therapeutic interventions in ASD.

“The present findings of impaired embodiment of others’ affective states might have implications for therapeutic interventions in ASD.”