Review Journal of Autism and Developmental Disorders (2018) 5:408–421 https://doi.org/10.1007/s40489-018-0149-1

REVIEW PAPER

Virtual Environments for Assessment of Social Exclusion in Autism: a Systematic Review

Eva Venturini1 & Thomas D. Parsons2

Received: 29 March 2017 /Accepted: 3 August 2018 /Published online: 17 August 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract This review aims to identify and systematically evaluate the use of virtual assessments of social exclusion in persons with autism spectrum disorders (ASD). The authors screened articles for inclusion in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Ten peer-reviewed studies were reviewed to understand the current status of empirically based evidence of social exclusion in persons with ASD. Most studies used self-report questionnaires to assess affect, mood, and distress following simulated social interactions using the Cyberball game. Five studies used neuro- imaging to identify neural correlates of social exclusion. Results reveal differences between persons with ASD and typically developing participants. Some discrepancy was noted between self-reports and the brain responses from persons with ASD.

Keywords Autism . Social exclusion . Assessment . Self-report . Brain responses . Cyberball

Persons with autism spectrum disorder (ASD) have impair- the social orienting impairments of autism reflect a distur- ments in social and communication skills, as well as repetitive bance of Bsocial executive^ functioning that involves frontal behaviors or thought process (American Psychiatric motivation, self-monitoring, and volitional attention regula- Association (APA) 2013). Prevalence estimates have in- tion (Mundy 2003; see also Mundy and Burnette 2005) creased dramatically in the last 20 years such that 1 in 59 Further, deficits appear to be found in temporal/parietal sys- children in the USA has been identified with this disorder tems that involve orienting and processing information about (Baio et al. 2018). Adults with ASD tend to have a social the social behaviors of others (Mundy and Newell 2007). orienting disturbance, whereas children with ASD display a Acknowledgement of these challenges has led to the devel- syndrome specific difficulty with attending to and processing opment of assessments that aim to measure functioning by social stimuli, such as faces or the direction of eye gaze. As a focusing on social skills, such as emotion recognition. Less result, effective evaluation of social cognitive functioning is often, assessments are based on social cognitive processing, an important clinical and public health issue. The social interpretation, and responses to social cues. Assessment of orienting deficits of persons with ASD may limit their capac- social skills and cognition has been performed using a variety ity for social learning at home and in school and also plays a of techniques and measures and has found mixed levels of role in their development of social competence and social success. Some studies have utilized observational techniques cognition (Dawson et al. 1998). Recent research suggests that and recorded the frequency and types of interactions (Hillier et al. 2007), while others have looked at conversational style during interview scenarios (Howlin and Yates 1999). Other * Eva Venturini studies use questionnaires to assess empathy and acceptance [email protected] by others (Hillier et al. 2007;HowlinandYates1999). An additional approach has involved social cognition perfor- Thomas D. Parsons mance measures that record behaviors (e.g., accuracy of re- [email protected] sponses) of participants engaging in social tasks (Golan and Baron-Cohen 2006; Turner-Brown et al. 2008). These assess- 1 Department of Human Sciences for Education, University of Milano-Bicocca, str. 8, Thomas Mann, 20162 Milan, Italy ment approaches may be somewhat limited by the lack of everyday social situations (Parsons 2014). 2 Department of Psychology, University of North Texas, Psychology Building (Terrill Hall)-1611 W. Mulberry St., Denton, TX 76201, A potential response to the difficulties of ecological va- USA lidity in social cognitive assessment of persons with ASD is Rev J Autism Dev Disord (2018) 5:408–421 409 to present stimuli using virtual environments that are being The virtual Cyberball game has also been extended to 3D used increasingly in the clinical and social sciences (Bohil non-immersive virtual environments (Bolling et al. 2011; et al. 2011;Parsons2015). Virtual environments can range Mavromihelaki et al. 2014; Venturini et al. 2016)andto3D from non-immersive 2D presentations to immersive 3D en- immersive virtual environment in which the participants wear a vironments presented with head mounted displays. The head-mounted display (HMD) for playing the game (Kassner et utility of virtual environments for assessment of persons al. 2012). These immersive 3D virtual Cyberball environments with ASD has led to a preliminary studies and reviews sug- have been developed to allow even greater levels of flexibility gesting that virtual environments may be ideal for the as- for manipulation of social information about the participant’s sessment of persons with ASD (Byom and Mutlu 2013; interactions with confederate avatars and virtual humans Parsons and Carlew 2016; Parsons et al. 2017). (Venturini et al. 2016; Wirth et al. 2010, 2011). Social cognition is important for accurate gauging of who This review aimed to identify and systematically evaluate the is connected to whom. For persons with autism, getting an use of social cognitive assessments of exclusion in persons with accurate read on social connections can be challenging when ASD. To the best of our knowledge, no systematic review has social relations must be discerned from observations of real- been carried out that pointedly focuses on the use of virtual time social interactions. Being excluded from social interac- environment-based social cognitive assessments of social pain/ tion can be distressing (Williams 2007a). Feelings of social exclusion in persons with ASD. We aimed to provide a system- pain and exclusion may occur whether one is rejected by real atic review of the studies that investigated results in social pain humans or by virtual humans in a virtual environment or social exclusion in persons with ASD: (1) explored the in- (Williams et al. 2000; Zadro et al. 2004). Given that persons struments or methodologies of social exclusion assessment used tend to value social connections (Williams 2007b), the expe- in experimental studies focused on persons with ASD, (2) ex- rience of social exclusion may prompt a desire for social re- amined the brain responses related to specific social stimuli in connection (Maner et al. 2007). While persons who have been studies of persons with ASD, and (3) interpreted differences excluded are motivated to reconnect, social cognitive deficits between self-reported evaluation and physiological arousal. may limit this process. There is a developing literature on psychosocial interventions A number of studies have used a 2D virtual Cyberball to enhance the social skills in daily life. It is known that social game (Williams et al. 2000) to assess social cognitive ap- interaction deficits in persons with ASD represent a core char- praisals of exclusion/ostracism. The virtual Cyberball game acteristic (Volkmar et al. 2014). Although this review did not is an experimentally controlled social cognitive assessment focus upon virtual environment interventions, there is valuable of exclusion that elicits affective (Wesselmann et al. 2012; assessment information provided that may increase understand- Williams 2007a), neurobiological (Eisenberger and Cole ing of social exclusion in studies of persons with ASD. The 2012), psychophysiological (Moor et al. 2010; Sijtsema et BOverview of the Studies^ and BParticipant Characteristics^ al. 2011), and hormonal (Geniole et al. 2011;Zwolinski sections are useful to understand the typologies of studies and 2012) responses. During the Cyberball task, the participant the specific features of persons in the clinical group. The BTasks controls an avatar that is either included (inclusion condition) and Assessment^ section provides an overview of the most or ostracized (exclusion condition) by two or three other ava- widely used instruments and methodologies in studies of per- tars controlled by the experimenter. Telling participants that sons with ASD. In the BDescription of Self-Report Results^ and the avatars are controlled by a computer does not change the BDescription of Neuroimaging Results^ sections, we present the effects of ostracism (Zadro et al. 2004). most significant results arising from included papers. Finally, in Results from neuroimaging studies have revealed that the BDiscussion^ section, we focused on the relevance of review being excluded from ball-tossing reliably evokes increased findings. Furthermore, we describe how these findings can relate activation of the dorsal anterior cingulate and anterior to the everyday experience of persons with ASD. The clinical insula, which correlates with self-reports of physical pain implications of the findings and potential future research direc- (Eisenberger 2012). While results from a recent meta- tions are also discussed. analysis suggest that the neural correlates of nociceptive stimuli and social rejection have some distinct patterns of activation, they still share commonalities (Cacioppo et al. Methods 2013). Rotge et al. (2015) meta-analytic review revealed that the virtual Cyberball game activated the dorsal anterior Inclusion and Exclusion Criteria cingulate circuit less than other experimental social pain tasks. Findings suggest that social pain following exclu- Authors collected and screened articles for inclusion in accor- sion in the virtual Cyberball game is less intense than the dance with the Preferred Reporting Items for Systematic social pain following more personal forms of social rejec- Reviews and Meta-Analysis (PRISMA) guidelines (Moher tion (Eisenberger 2015). et al. 2009). The authors independently selected paper 410 Rev J Autism Dev Disord (2018) 5:408–421 abstracts and titles and analyzed the full papers that met the by social interaction. Descriptive data for the sample were inclusion criteria, resolving disagreements through consensus. coded to include mean age, percent male, number of individ- Authors excluded conference proceedings, review articles, uals diagnosed with ASD, and number of individuals that factor analyses, dissertations, case studies, editorials, and were typically developing (TD) controls. commentaries. Established criteria were empirical studies published in peer-reviewed English-language publications. Studies includ- Results ed participants diagnosed with ASD (including those persons described as having high-functioning autism and/or The authors found 126 citations using the string (BAutism^ OR Asperger’s syndrome). The specific topic of studies was as- BAsperger^) AND (BSocial Exclusion^ OR BSocial inclusion^ sessment of social pain, ostracism, and/or social exclusion. OR BSocial Pain^ OR BOstracism^) (for more details see Table Authors excluded studies that did not use assessment tools 1). After they screened titles and abstracts only ten articles such as survey or measures of brain function. remained. Tables 2 and 3 provide a summary of the ten studies that involved assessment of social exclusion/pain in persons with Search Strategy ASD. The studies are categorized by authors, date of publication, stimuli, (instruments used for assessment), type of social interac- A systematic search of published studies was undertaken in the tion, results of the studies, and interpretation of results. following databases: Scopus/Pubmed and Web of Science (Web of Knowledge) in November 2015 and the authors found Overview of Studies 125 records. The search was repeated in January 2017, and one new document was found. As a result, the final number of All articles were published in 2017 or before. Most of the records was 126. The search was completed using the string studies were conducted in the USA. Two were conducted in (BAutism^ OR BAsperger^) AND (BSocial exclusion^ OR Germany and two in France. One study was conducted in BSocial Inclusion^ OR BSocial Pain^ OR BOstracism^). For Greece. Consistent with inclusion criteria, all studies included more details see Table 1. individuals diagnosed under DSM-IV-TR (APA 2000)and/or The authors independently screened titles and abstracts of DSM-5 (APA 2013) criteria for ASD. All studies used self- all results and excluded inconsistent articles. Then, each au- report questionnaires to assess affect, mood, and distress thor examined the full text of residual articles to determine caused by social interactions. Five of ten research studies used whether they met all the inclusion criteria. This resulted in a brain assessment metrics to measure social exclusion. Most of total of ten articles (for more details see Fig. 1). the studies used the 2D virtual Cyberball game to assess the impact of social exclusion/ostracism in persons with ASD. Data Extraction Participant Characteristics The data extracted from each study meeting inclusion criteria were as follows: author(s), year, sample(s), assessment tools, A total of 200 participants with ASD diagnosis were included type of social interaction, self-report results, and neuroimag- in the ten studies (Tables 2 and 3). ing results. To emphasize the most relevant results, studies In six studies, the mean age of participants was 13 years. In were categorized based on the use of assessment tools, self- one study, there were two different samples, with mean ages of report, and measures of brain function. Table 2 presents stud- 9 and 24 years, respectively. In two Byoung adults^ studies ies reflecting affective responding to social interactions. Table (Krach et al. 2015;Paulusetal.2013), age was not reported. 3 presents results from studies assessing brain activity caused As is typical with studies of persons with ASD, males made

Table 1 Search strategy details Autism/Asperger AND “Social exclusion”“Social inclusion”“Social pain”“Ostracism” TOT

Scopus/Pubmed 42 65 9 10 126 Web of Science 24 37 4 10 75 Non duplicated 33 Excluded (after reading 20 title and abstract) Excluded (after applying 3 inclusion criteria) Included 10 Rev J Autism Dev Disord (2018) 5:408–421 411

Scopus/Pubmed Web of Science (Web Andari et al. (2010, 2016) used a variant version of this game January 2nd, 2017 of Knowledge) nd by adding photographs corresponding to digital players. One 126 citations January 2 , 2017 B ^ 75 citations study included a neutral third player. Oxytocin was admin- istered to participants with ASD. Bolling et al. (2011)modi- fied the classical version of Cyberball by giving digital players gender and added a comparable game (Cybershape) to assess 33 non-duplicated Citations Screened for rule violations. In the remaining two studies (Krach et al. 2015;Paulusetal.2013), used pictures of vicarious embar- rassment and social/physical pain. To assess affective responding, four studies used the Needs 20 Papers Inclusion/Exclusion Threat Scale with Manipulation check item (Van Beest and excluded after Criteria Applied Williams 2006; Williams et al. 2000) after playing Cyberball. Title/Abstract screen Bolling et al. (2011)) used an abbreviated version of this tool. Andari et al. (2010, 2016)) asked participants to estimate their sentiments of Btrust^ and Bpreference^ with respect to the fictitious players. In the Paulus et al. (2013) study, participants 13 Papers 3 Papers were asked to indicate their personal experience on a rating assessed for excluded after scale ranging from 1 Bnot at all^ to 7 Bvery strong.^ In eligibility full text screen Sebastian et al. (2009)) study, the State/Trait Anxiety Inventory (Spielberger et al. 1983) was used to assess anxiety. Twyman et al. (2010) assessed bullying behavior and vic- timization experiences in participants using the Reynolds Inclusion/Exclus Bully-Victimization Scale (Reynolds 2003). Furthermore, ion Criteria in five studies, researchers used fMRI (Andari et al. 2016; Applied Bolling et al. 2011; Krach et al. 2015;Mastenetal.2011) and EEG (McPartland et al. 2011) for assessing brain activation of social exclusion.

10 Included full-text Description of Self-Report Results Fig. 1 Systematic search results (adopted PRISMA flow diagram) While differences were not found in comparisons of self- up more than 90% of study samples that reported demo- reported feelings between persons with ASD and graphics pertaining to sex. participants that were TD, some studies did find differences All participants had received a diagnosis of ASD by clini- in mood responses. Ostracism did not modulate overall mood calICD-10(WorldHealthOrganization[WHO]1992)con- in persons with ASD. Peristeri et al. (2014; see also Sebastian sensus or by DSM-IV-TR (APA 2000) or DSM V (APA 2013) et al. 2009) suggest that this may be due to the possibility that criteria. Furthermore, in nine of ten studies, participants were persons with ASD may not interpret appropriately their cur- diagnosed using the Autism Diagnostic Observation Schedule rent emotional state with subsequent deficits in understanding (ADOS) (Lord et al. 2000) and the Autism Diagnostic the affective aspects of emotion words in the self-report ques- Interview—Revised (ADI-R) (Lord et al. 1994)orASDI tionnaire. While exclusion by peers may result in persons with (Asperger Syndrome Diagnostic Interview) (Gillberg et al. ASD feeling just as rejected as their TD counterparts, the 2001). In the study by Paulus et al. (2013), the German short persons with ASD lackaday lack insight into how the ex- version of the Autism Spectrum-Quotient questionnaire (AQ- perience affected their current mood. In this regard, studies k) (Freitag et al. 2007) was used. Only one study (Twyman et of Andari et al. (2010, 2016) are very interesting. They al. 2010) was conducted without the use of such instruments. demonstrated that oxytocin administration activated appro- ’ Instead, the authors relied upon expert clinical judgment. priate emotional responses for partners feedback at the behavioral level in persons with ASD, attributing different emotional intentions to the behavior of each partner. Tasks and Assessment Atypical emotional and behavioral responses can be nor- malized with intranasal oxytocin administration, enhanc- The Cyberball paradigm, original version, was used in five ing the person with ASD’s ability to understand the mean- studies to represent a social exclusion/ostracism situation. ing of social cues in an interactive context. 412 Table 2 Feelings of social exclusion in studies of persons with autism

Author(s) Sample(s) Task(s) Social interaction Assessment tools Self-report results Interpretation

Andari et al. 13 HF-ASD all Cyberball + oxytocin Bface Social exclusion Item estimating self-sentiments of Under oxytocin, patients spent more Oxytocin may reduce the fear or (2010) males perception tasks^ Prosocial behavior Btrust^ and Bpreference^ with time looking at the face pictures. anxiety induced by face stimuli in Age = n.s. respect to the fictitious players Under oxytocin patients engaged patients. TD = 0 more often in exchanges with the Oxytocin enhanced patients’ ability player who reciprocated strongly, to process socially relevant cues and they exhibited emotional and acquire their meaning in an responses congruent with this interactive context. behavior. Andari et al. 20 ASD Cyberball + oxytocin Bface Social exclusion Item estimating self-sentiments of In the oxytocin condition, The authors speculate that OT (2016) 19 males perception tasks^ Prosocial behavior Btrust^ and Bpreference^ with participants reported more trust administration is likely to Age mean = 26.37 respect to the fictitious players toward the fair player as remediate cognitive and neural SD = 8.45 TD = 0 compared to the unfair player. deficits through mechanisms that Oxytocin administration activated are typically engaged by adults appropriate emotional responses without ASD for partners’ feedback at the behavioral level in ASD, attributing different emotional incentives to the behavior of each partners. Bolling et al. 24 ASD Cyberball Social exclusion Abbreviated version of Needs No differences in exclusion between Thedifferenceinruleviolation (2011) 15 male Cybershape Rule violation Threats Scale ASD and TD groups. responses may reflect the Age 7–17 Social Responsiveness Scale Following rule violation, ASD inflexible adherence to routines or 24 TD participants reporting rituals representing rigid, 17 male significantly greater distress than restricted behavior in ASD. Age 9–17 TD participants. Any correlations in ASD between self-reported distress and brain activation to exclusion or rule violation (versus fair play). Krach et al. 16 ASD Pictures representing Social pain Item evaluating the intensity of In HC, self-reports on the intensity ASD compensate for their reduced (2015) 16 HC physical pain (56), social Physical pain vicarious embarrassment of their SP experience showed ability to access embodied signals

Age > 18 pain (40) and neutral Item estimating the intensity of significant coupling with activity by means frigidly learning and 5:408 (2018) Disord Dev Autism J Rev (10) physical pain of the ACC and AIC memorizing social rules and ASD did not base their self-report on conventions the embodied representations of affect in this network. Masten et al. 19 HF-ASD Cyberball Social exclusion Needs Threats Scale No differences between ASD and ASDfeeljustasrejectedastheirTD (2011) 18 males Item of manipulation check controls on self-reported feelings counterparts when they are Age mean = 14; of distress following the exclusion excludedbypeers. SD = 2.4 round of Cyberball. 17 TD 15 males Age mean = 13.6;

SD = 2.5 – 20 ASD males Cyberball Social exclusion Needs Threats Scale 421 e uimDvDsr 21)5:408 (2018) Disord Dev Autism J Rev Table 2 (continued)

Author(s) Sample(s) Task(s) Social interaction Assessment tools Self-report results Interpretation

McPartland Age = 5–15 Scale tapping personal attributions Both groups reported similar levels Modifications to the paradigm to et al. 34 TD about other players of distress in response to social enhance realism may have (2011) 17 males exclusion. increased investment on the part Age = 8–15 of participants with ASD, influencing self-reported mood. Paulus et al. 32 ASD (8 HD-ASD, 30 vignettes of vicarious Vicarious Items indicating personal ASD showed significantly lower The empathy trait should be (2013) 22 AS and 2 embarrassing situations embarrassment experience about the vicarious vicarious embarrassment when responsible of capacity to

atypical autism) 10 vignettes of neutral embarrassment they observe intentional comprehend vicarious – 421 Age = young adults situations violations of social norms. embarrassment experiences in Both groups reported no differences ASD. in response to neutral situations. ASD with high trait of empathy report stronger vicarious embarrassment experiences. Peristeri et 10 HFA Cyberball Social Exclusion Needs Threats Scale The ostracism condition affected HFA adults have probably al. (2014) 8 males Item of manipulation check self-reported mood and three out responded in a perseverative Age mean = 9.4; of four social needs in both manner and HFA children’shave SD = 1.9 healthy groups, while did not revealed difficulties with 10 TD modulate overall mood in HFA understanding how the ostracism 7 males groups. Indeed, patients failed to experience affected their current Mean = 9.3; interpret appropriately their emotional state. SD = 1.6 current emotional state with an 11 HFA impact on understanding affective 10 males aspects of emotion words in the Mean = 24.7; self-report questionnaire. SD = 10.5 11 TD 10 males Mean = 28.2; SD = 10.8 Sebastian et 13 ASC Cyberball Social exclusion Needs Threats Scale Both groups recognized when they ASC group may have been equally al. (2009) (all males) Age Item of manipulation check are being excluded from a social affected by the ostracism mean = 16.9 16 STAI-S situation, reporting similar effects condition as TD controls, but TD (all males) of ostracism on anxiety and on might have lacked insight into Age mean = 16.9 need threat. how the experience affected their ASC did not report any differences current mood. in overall mood following ostracism, while mood was loweredbyostracisminthe control group. Self-reported need threat did not differ between groups for self-esteem, belonging and

control. In contrast, in the ASC 413 414 Rev J Autism Dev Disord (2018) 5:408–421

Other differences between persons with ASD and persons that are TD were found in studies assessing rule violation (Bolling et al. 2011). Persons with ASD reported significantly greater distress. Krach et al. (2015) highlighted that individ- uals with ASD did not base their self-report on the embodied representations of affect (as did persons in the TD group), but on memory process. Paulus et al. (2013)emphasizedthatboth groups reported no differences in response to neutral situa-

in establishing and maintaining peer friendships such as those with ADHD, ASD, and LD, ostracism may be particularly devastating. tions, but participants with ASD showed significantly lower Children who already have difficulty vicarious embarrassment when they observed intentional vio- lations of social norms. Furthermore, the research on bully ypically developing victimization (Twyman et al. 2010) found that persons with ASD reported the highest percentages of clinically significant victimization and ostracism experiences when compared to other clinical or healthy populations. Lastly, following the exclusion round, three studies (Bolling et al. 2011;Mastenet esults Interpretation al. 2011;McPartlandetal.2011) reported that both groups experienced distress following social exclusion, but there group meaningful existence was higher. percentages of clinically significant victimization AND ostracism experiences were no group differences. ASD group reported the highest Description of Neuroimaging Results

Regarding the differences in neuroimaging results, between persons with ASD and persons in the TD groups, all studies reported less activity during exclusion versus inclusion among participants with ASD in brain regions involved in emotion Bully-Victimization

’ processing, including anterior cingulate cortex and anterior insula. Furthermore, Masten et al. (2011) found less activity essment tools Self-report r Scale during exclusion in regions previously shown to be negatively Pilot ostracism scale. Reynolds related to distress during exclusion (i.e., ventrolateral prefron- tal cortex, ventral striatum). This differential engagement of neural circuitry in response to peer rejection could also be related to peer rejection experiences that adolescents with ASD have in their daily lives. They may be more habituated victimization ostracism to be rejected by novel groups of peers. The study by Bolling et al. (2011) showed that only persons with ASD reported an activation to rule violation in bilateral caudate, superior tem- poral sulcus, and anterior insula. In Krach et al. (2015), only h-function autism spectrum disorder; HC = healthy controls; ASC = autism spectrum conditions; TD = t persons with ASD showed domain-specific decrements in the neurobiological response of vicarious social pain. Only one study (McPartland et al. 2011) analyzed temporal dynamics of brain activity associated with social exclusion and reported

Cyberball Bullying peer that in persons with ASD, there is a dissociation between reported distress and neural responses and differentiation of rejection at an earlier frontal P2 component. The temporal course of the early positivity (P2) indicates a role in more basic cognitive processing, such as visual attention in persons with ASD. Lastly, the study using oxytocin administration ASD Age mean = 11 (294 participants) 32 (Andari et al. 2016) showed that acute intranasal oxytocin

) helped persons with ASD to discriminate between different (continued) social contexts and social values associated to faces (Kirsch 2010 et al. 2005), by modulating the brain activity of key emotional al. ( Table 2 Author(s) Sample(s) Task(s) Social interaction Ass Twyman et Note: ASD = autism spectrum disorder; HF-ASD = hig regions (amygdala and hippocampus). During social e uimDvDsr 21)5:408 (2018) Disord Dev Autism J Rev Table 3 Neural correlates of social exclusion in studies of persons with autism

Author(s) Sample(s) Task(s) Social interaction Assessment Neuroimaging results Interpretation tools

Andari et al. 20 ASD Cyberball + oxytocin Bface Social exclusion fMRI IN-OT helped ASD to discriminate OT inhibits amygdala activity during the (2016) 19 males perception tasks^ Prosocial behavior between different social contexts and perception of faces and modulates Age mean = 26.37 social values associated to faces, by stress responses as a function of SD = 8.45 TD = 0 modulating the brain activity of key positive social interactions. emotional regions (amygdala and This region is known for its role in hippocampus). reward value representation.

During social reciprocity, OT delivery – prompted the activity of anterior OFC 421 in individuals with ASD. Bolling et al. 24 ASD Cyberball Social exclusion fMRI ASD showed activation to social The finding that posterior insula responds (2011) N =15male Cybershape Rule violation exclusion only in retrosplenial cortex to exclusion in TD participants may Age 7–17 and left precentral gyrus. reflect a more visceral response to 24 TD ASD showed similar activation to TD social exclusion N =17male peers in dorsomedial and lateral Activation of anterior insula to rule Age 9–17 prefrontal cortex and right parietal violationinASDmayreflectamore cortices. cognitive, conscious emotional Only ASD showed activation to rule response. violation in bilateral caudate, superior temporal sulcus, and anterior insula. Krach et al. 16 ASD Pictures representing physical Social pain fMRI In ASD, domain-specific decrements in ASD use an alternative route to obtain the (2015) 16 HC pain (56), social pain (40), Physical pain the neurobiological response of same behavior and we provide the first Age > 18 and neutral (10) vicarious social pain, non-significant evidence for differences in the for physical pain. underlying neurobiological Reduced activation of the ACC and AIC mechanisms that link neural activation as well as by the pupillary responses. with behavior In contrast, in the context of vicarious physical pain, no peculiarities were found in any of the neurobiological responses. Masten et al. 19 HF-ASD Cyberball Social exclusion fMRI ASD display hypoactivation in brain This differential engagement of neural (2011) 18 males regions involved in emotion circuitry in response to peer rejection Age mean = 14; SD = 2.4 processing, including the sub ACC could also be related to a number of 17 TD and AI, specifically when performing qualitative factors related to peer 15 males a range of social cognitive tasks. rejection experiences that adolescents Age mean = 13.6; SD = 2.5 Less activity during exclusion versus with ASD have in their daily lives: inclusion among adolescents with maybemorehabituatedtoberejected ASD compared to controls in sub ACC or may expect to be rejected when they and AI, as well as in regions interact with novel groups of peers. previously shown to be negatively related to distress during exclusion (i.e., VLPFC, VS). McPartland 20 ASD males Cyberball Social exclusion EEG Temporal dynamics of brain activity The absence of differential response to et al. Age = 5–15 associated with social exclusion in exclusion versus Bnot my turn^ at the (2011) 34 TD ASD reveal a dissociation between LSW suggests that children with ASD 415 416 Rev J Autism Dev Disord (2018) 5:408–421

reciprocity, intranasal oxytocin delivery prompted the activity of anterior orbitofrontal cortex in individuals with ASD and modulates stress responses as a function of positive social interactions (Chen et al. 2011).

Discussion

This review set out to investigate virtual environment-based

might be failing to makedistinctions critical based on social context. positivity (P2) indicates a rolebasic in cognitive more processing, such assual vi- attention in ASD. social cognitive assessments of social exclusion/pain for per-

The temporal course of the early sons with ASD. All the studies assessed social exclusion/os-

nterior cingulate cortex; subACC = subgenual tracism. This review also reports behavioral and neuroimaging results studies of social exclusion (or ostracism) using 2D virtual environments. Most of the studies used the virtual Cyberball paradigm (Williams et al. 2000) to present stimuli for social interaction. Furthermore, the review points to a po- s Interpretation tential gap between the ways in which persons with ASD evaluate themselves and their emotions.

Results from Self-Report Data reported distress and neural response in ASD. responses between ASD and TD. children with ASD showed differentiation of rejection at anfrontal earlier P2 component, although this response also did not associatetheir with reported experience of rejection. Difference in the temporal course of brain In contrast to their typical peers, the Neuroimaging result Self-report data suggest that individuals with ASD are as able as TD controls to recognize when they are being excluded from a social situation. In the studies that used the 2D virtual Cyberball paradigm, both groups reported elevated levels of

tools distress following social exclusion. In these cases, there were no group differences. Moreover, in some studies, ostracism did not modulate overall mood in persons with ASD. Contrariwise, some studies found differences in mood re- sponses. Peristeri and et al. (2014; see also Sebastian et al. 2009) provide as a possible explanation the perspective that ocial interaction Assessment

teral prefrontal cortex; and VS = ventral striatum persons with ASD failed to interpret appropriately their cur- rent emotional state, which impacted understanding of affec- tive content found in emotion words used for the self-report questionnaires. Although persons with ASD may feel just as rejected as their TD counterparts when they are excluded by peers, they might have lacked insight into how the experience affected their current mood. The works by Andari et al. (2016; 2010) may help to explain these findings. They found some lly developing; EEG = electroence phalography; fMRI = functional magnetic resonance imaging; ACC = a preliminary results that show atypical emotional and behav- ioral responses can be normalized with intranasal oxytocin administration, by modulating the brain activity of key emo- tional regions (amygdala and hippocampus) and by reducing their anxiety induced by face stimuli. Indeed, the authors con- firmed that oxytocin enhanced the ability of persons with ate cortex; AI = anterior insula; VLPFC = ventrola ASD to elaborate socially significant signals and get their 15 – meaning within an interactive context. The degree of self-reported need threat did not differ be-

17 males Age = 8 tween groups for self-esteem, belonging, and control. Sebastian et al. (2009), however, found greater threat in the (continued) persons with ASD, compared with controls, on the meaning- ful existence scale. This may be due to the greater likelihood Note: ASD = autism spectrum disorder; TD = typica Table 3 Author(s) Sample(s) Task(s) S portion of the anterior cingul that TD participants would have well-developed support Rev J Autism Dev Disord (2018) 5:408–421 417 networks that defend against feelings of neglect, meaningless, superior temporal sulcus, and anterior insula in conjunction and/or non-existence during a short virtual episode of ostra- with the vicarious social pain paradigm. Moreover, the authors cism. Meanwhile, persons with ASD may have lacked this found that the children with ASD showed differentiation of resource. Furthermore, group differences were found using a rejection at an earlier frontal P2 component, this reduced am- modified Cyberball game (Bolling et al. 2011). Persons with plitude at the P2 for rejection events suggests attenuated en- ASD reported significantly greater distress following rule vi- gagement of attentional resources during the experience of olation and intentional violations of social norms. The differ- exclusion in these participants. ence in rule violation responses may reflect rigid adherence to Paulus et al. (2013) found that only persons with ASD had routines or rituals typical of restricted behavior in persons with domain-specific decrements in the neurobiological response ASD (APA 2000). for this domain. Andari et al. (2016, 2010) demonstrated that Lastly, initial results from Krach et al. (2015) suggest that oxytocin fosters a first level of prosocial approach by over- individuals with ASD did not base their self-report on the turning the main deficit of persons with ASD, namely the lack embodied representations of affect, but on memory process. of eye contact. Moreover, oxytocin enhances affiliation partly The behavioral response to social pain may dissociate from by means of the reduction of the fear of social unfaithfulness the neurobiological embodiment of another’s affect. This con- and the elimination of avoidance behavior. This process re- cept recalls clinical observations that persons with ASD com- duces the activity of the amygdala, thus leading to a decrease pensate for their scarce ability to access the embodied signals of fear responses (Kirsch et al. 2005;Petrovicetal.2008). It is through processes of strict learning and memorization of so- possible that persons with ASD have hidden social skills and cial rules (Baron-Cohen et al. 2003; Klin et al. 2003). The that oxytocin may endorse social engagement behavior by authors emphasize the absence of general interference in peo- eliminating fear and mistrust. ple with ASD in the attribution of meaning to emotions, espe- Krach et al. (2015) hypothesized that in complex social cially in simple social situations, while increasing the difficul- situations persons with ASD may fail to intuitively access ty in interpreting complex social situations. the embodied representation of affect. This may be particular- One study (Twyman et al. 2010) found that persons with ly apparent in situations requiring representation of another’s ASD reported the highest percentages of clinically significant affective experience necessitates the integration of contextual victimization and ostracism experiences in respect to other demands. This hypothesis is supported by their results show- clinical or healthy populations. They may lack quality friend- ing that in healthy controls, self-reports findings of social pain ships to protect them from bullying. Indeed, individuals with experience match with activity of the anterior cingulate and ASD report higher degrees of loneliness than TD peers. anterior insula, brain regions associated with embodied af- Furthermore, they present a poorer understanding of the rela- fects. In contrast, individuals with ASD did not base their tionship between loneliness and social interaction. Persons self-report on the embodied representations of affect in this with ASD have difficulties in beginning and maintaining network, but exhibited a significant association with the hip- friendships. As a result, ostracism may be experienced as es- pocampus, the key region for memory processes. pecially difficulty (Bauminger et al. 2003). Comment on the Results Results from Neuroimaging Data To understand these results, it is necessary to examine the All studies using the virtual Cyberball paradigm reported literature concerning studies on self-report for persons with group differences. Masten et al. (2011) found a positive cor- ASD. Research has revealed that individuals with ASD tend relation between subanterior cingulate and distress in persons to have limited self-awareness as a component of their disabil- with ASD. In particular, a positive correlation was found be- ity. The reliability and validity of self-report measures in this tween the ventrolateral prefrontal cortex and distress. This population are unclear (Lainhart and Folstein 1994; Lainhart positive correlation may reflect an ineffective attempt to reg- 1999). Even though individuals with ASD are commonly be- ulate distress resulting from peer rejection in persons with lieved to have difficulty processing their own and other peo- ASD. Results from temporal dynamics of brain activity asso- ple’s emotions, authors (Berthoz and Hill 2005) have sug- ciated with social exclusion and reporting in participants with gested that individuals with ASD more likely show a different ASD revealed a dissociation between reported distress and approach to processing their emotions—rather than an ab- neural responses and differentiation of rejection at an earlier sence of this processing. Moreover, there is no commonly frontal P2 component. This suggests the importance of tem- used self-report measure valid for individuals with ASD poral dynamics in revealing processing strategies in typical (Mazefsky et al. 2011). Some results derived from the self- and atypical development (McPartland et al. 2011). The rule report of emotional responses in individuals with ASD lead to violation paradigm (Bolling et al. 2011) showed that only doubts about the validity of this approach. Researchers dis- participants with ASD had activation in bilateral caudate, covered that both persons with ASD and their TD counterparts 418 Rev J Autism Dev Disord (2018) 5:408–421 obtained similar physiological results from emotional stimuli, exclusion (Andari et al. 2010;VanDerMeulenetal. but different results in self-reports (Ben Shalom et al. 2006). 2016), others have evolved Cyberball into a 3D virtual Despite the several existing potential interpretations of said environment (Mavromihelaki et al. 2014; Venturini et al. results, it may be the case that persons with ASD struggle in 2016). In the 3D virtual reality versions of Cyberball, so- identifying their own emotions. The analysis of the self-report cial information about the confederates’ avatars can be ma- tools used in this research suggests that individuals with ASD nipulated to ensure a greater identification with (or differ- could report their own psychiatric symptoms to a certain level, entiation from) the participant (Bolling et al. 2011; but this would not be enough for clinical diagnostic purposes Venturini et al. 2016). Furthermore, Kassner et al. (2012) (Mazefsky et al. 2011). created an immersive virtual environment version that im- In line with previous research, the studies considered in merses the participant into an interactive simulation. This this review show differences in responses to self-report in change induced effect sizes that were medium to large in the two groups (persons with ASD and TD) may be due to magnitude of feelings of ostracism. This paradigm could the heterogeneity of symptoms in persons with ASD. be further implemented by including the variables of gen- There are differences in neurophysiological results. der and age to carry out trans-cultural studies. Furthermore, in some cases, there is a discrepancy be- Immersive 3D Cyberball paradigms may offer enhanced tween what was reported by self-evaluation and the find- ecological validity to obviate some of the ambiguities found ings from brain responses within persons with ASD. It in the literature. While the 2D Cyberball paradigm has been seems clear that the measures of brain function revealed widely used, some of the less robust findings may reflect the important group differences otherwise undetectable with fact that 2D versions of the Cyberball task lack the everyday behavioral methods alone. Persons with ASD showed dif- realism and ecological validity that are now available in to- ferentiation of rejection at an earlier frontal P2 compo- day’s immersive 3D virtual environments. Kassner et al. nent, although this response did not associate with their ( 2012) proposed an immersive virtual environment version reported experience of rejection (Bolling et al. 2011). of Cyberball, in which participants wear a HMD to display Given this lack of clarity, it is important that focus be the virtual environment. Results revealed that the more placed on more refined experimental paradigms that may immersive virtual environment induced feelings of ostracism reveal the peculiarities in the neural systems of functional in participants. Data from this study suggest that not only does architecture in persons with ASD. ostracism in this environment have the same negative effects Since children with ASD are vulnerable to social exclusion as in other environments, but these effects are powerful. Other and are exposed to its emotional and psychological conse- virtual reality desktop versions (Bolling et al. 2011; quences (McPartland et al. 2011), this topic requires further Mavromihelaki et al. 2014; Venturini et al. 2016)havebeen discussion. The American Academy of Pediatrics (AAP 2009) developed to allow even greater levels of flexibility for ma- has recognized bullying and victimization as serious problems nipulation of social information about the participant’s and has updated a policy statement on youth violence to re- interactions with confederate avatars and virtual humans mark the need for health care providers who can appropriately (Wirth et al. 2011). The inclusion of virtual humans en- deal with violence-related problems. hances the Cyberball paradigm because it allows for ad- The Cyberball paradigm is used in several studies of so- ditional social information such as non-verbal (e.g., eye- cial exclusion. Currently, more than 5000 subjects partici- gaze) information that has been found to convey ostra- pated studies utilizing this paradigm, and it is important to cism (Wirth et al. 2010). Furthermore, the immersive vir- note that even a few minutes of ostracism in this context can tual environment Cyberball paradigm offers researchers produce strongly negative emotions (Williams 2009). The the ability to control aspects (proxemics and non-verbal effects of ostracism produced be the relatively cartoonish communication) of the social context that cannot be ac- figures found in the 2D Cyberball platform are as impactful complished in minimalist ostracism paradigms. as those caused by ostracism occurring in a face-to-face setting; moreover, enduring ostracism by excluded partici- Clinical Implications pants can be as painful as when individuals are ostracized by those who are similar to them (Gonsalkorale and Williams In line with previous research (Berthoz and Hill 2005; 2007). Starting from this paradigm, researchers discovered Mazefsky et al. 2011), the studies considered in this review that the brain activations found during exclusion conditions showed differences in responses to self-reports between par- are the same as those activated when people experience ticipants with ASD and those that were TD. In some cases, physical pain (Eisenberger et al. 2003). discrepancies were found between what was reported by persons Other studies are emerging that develop the 2D virtual with ASD during self-evaluations and findings from physiolog- Cyberball paradigm. While some simply add a fourth ical arousal or brain measures. Given this lack of clarity, it is Bneutral^ player to verify the level of understanding of important that future studies develop more refined experimental Rev J Autism Dev Disord (2018) 5:408–421 419 paradigms that may reveal the peculiarities in the neural systems systematic review. International Journal of Environmental – of functional architecture in persons with ASD. Research and Public Health, 11, 7767 7802. https://doi.org/10. 3390/ijerph110807767. Furthermore, recent research has revealed that virtual envi- Baio, J., et al. (2018). 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