Linnea Bjerregaard Pedersen

Ali Adjorlu

Valentin Bauer
email: valentin.bauer@limsi.fr

Exploring the Possibilities of Music Therapy in Virtual Reality: Social Skills Training for Adolescents with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by profound communication and social interaction deficits. It can lead to social anxiety and depressive thought patterns, leaving the individual unable to be a productive member of society. Music therapy is a method that applies musical experiences and the relationships that develop through the sessions to train communication skills, thus addressing one of the core difficulties of ASD. However, music therapy requires musical instruments that are not always easily accessible and can be an anxiety-inducing experience. This paper presents a multiplayer virtual reality application designed to allow a music therapist to help a child develop social skills in a virtual environment through musical activities. The application is designed in collaboration with two music therapists and two psychologists and includes a qualitative evaluation of the application.

INTRODUCTION

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that is mainly characterised by social communication and interaction difficulties [START_REF] Lord | Autism spectrum disorder[END_REF]. These deficits can lead to social anxiety [START_REF] Bellini | The development of social anxiety in adolescents with autism spectrum disorders[END_REF], isolation [START_REF] Chamberlain | Involvement or isolation? The social networks of children with autism in regular classrooms[END_REF], and depression [START_REF] Ghaziuddin | Depression in persons with autism: Implications for research and clinical care[END_REF]. Music therapy (MT) has shown potential in increasing social communications skills in individuals on the autism spectrum 1 . More specifically, MT successfully trains verbal and non-verbal communication, especially if the intervention starts during the childhood of autistic individuals [START_REF] Provenzano | Music therapy for communication in children with autism spectrum disorder[END_REF].

Compared to verbal stimuli, music-based interventions can increase the child's engagement, attention, as well as their self-esteem [START_REF] Adjorlu | Virtual reality music intervention to reduce social anxiety in adolescents diagnosed with autism spectrum disorder[END_REF][START_REF] Gal | Using Innovative Technologies as Therapeutic and Educational Tools for Children with Autism Spectrum Disorder[END_REF][START_REF] Geretsegger | Music therapy for people with autism spectrum disorder[END_REF]. However, MT can be a socially anxiety-inducing experience for autistic children [START_REF] Bellini | The development of social anxiety in adolescents with autism spectrum disorders[END_REF], as well as time-consuming for the parents, thus risks discouraging families to continue the MT sessions due to not seeing immediate progress [START_REF] Provenzano | Music therapy for communication in children with autism spectrum disorder[END_REF]. By replacing the users' physical sensory information with virtually created ones, Virtual Reality (VR) can be used to 1 'Autistic person' and 'person on the autism spectrum' are endorsed terms by autistic adults and stakeholders, i.e., parents [START_REF] Bottema-Beutel | Avoiding ableist language: Suggestions for autism researchers[END_REF][START_REF] Kenny | Which terms should be used to describe autism? perspectives from the uk autism community[END_REF].

place the users inside a relevant, interactive virtual environment (VE) within which they can receive appropriate interventions [START_REF] Adjorlu | Virtual reality therapy[END_REF]. This enables the opportunity to perform MT from the social safety of the user's home and without the need for resources to access physical MT sessions and instruments. So far, most research on VR interventions for autism has focused on training target behaviours through simulated real-life situations [START_REF] Burke | Using virtual interactive training agents (ViTA) with adults with autism and other developmental disabilities[END_REF][START_REF] Ip | Virtual reality enabled training for social adaptation in inclusive education settings for school-aged children with autism spectrum disorder[END_REF], including costly or potentially threatening scenarios [START_REF] Parsons | The potential of virtual reality in social skills training for people with autistic spectrum disorders[END_REF].

However, the potential of VR to extend MT sessions for autistic children by alleviating social interaction difficulties [START_REF] Johnston | Innovative computer technology in music based interventions for individuals with autism -moving beyond traditional interactive music therapy techniques[END_REF], remains largely unexplored. To the authors' knowledge only few VR MT studies have been performed so far [START_REF] Shahab | Utilizing social virtual reality robot (V2R) for music education to children with high-functioning autism[END_REF][START_REF] Bryce | The Sense of Auditory Presence in a Choir for Virtual Reality[END_REF][START_REF] Brungardt | Virtual reality-based music therapy in palliative care: A pilot implementation trial[END_REF]. Shahab et al. [START_REF] Shahab | Utilizing social virtual reality robot (V2R) for music education to children with high-functioning autism[END_REF] tested a VR environment consisting of a robot avatar and a virtual xylophone with five children, suggesting promising outcomes regarding musical ability and cognitive skills. Bryce et al. [START_REF] Bryce | The Sense of Auditory Presence in a Choir for Virtual Reality[END_REF] exposed four children to a 360 • video of a children's choir, but findings were inconclusive. Brungardt et al. [START_REF] Brungardt | Virtual reality-based music therapy in palliative care: A pilot implementation trial[END_REF] conducted a pilot study with 17 patients in palliative care. The intervention received positive feedback and was accepted and found usable by the patients. When using VR applications for individuals with ASD, approaches have to be individualised according to the specific needs, to increase the overall acceptability [START_REF] Bryce | The Sense of Auditory Presence in a Choir for Virtual Reality[END_REF][START_REF] Parsons | Whose agenda? Who knows best? Whose voice?' Co-creating a technology research roadmap with autism stakeholders[END_REF]. To that respect, involving stakeholders in the design process while offering collaborative designs is advised [START_REF] Parsons | Whose agenda? Who knows best? Whose voice?' Co-creating a technology research roadmap with autism stakeholders[END_REF].

This project follows the philosophy of user-centered design [START_REF] Preece | Interaction Design: Beyond Human-Computer Interaction[END_REF], meaning that therapists working with autistic individuals on a daily basis are included early in the design process. In this paper, we present the design process and validation of a collaborative MT multiplayer platform that aims at allowing music therapists to perform MT sessions with an autistic child in VR. The overall design process is divided into four segments, which are successively described in the following sections. First, to create the initial design of the VE, an informal preliminary interview was conducted with two music therapists. (section 2). Second, one of the music therapists who participated in the preliminary interview took part in the evaluation of this first design version (section 3). Third, frequent meetings were organised with two psychologists over four consecutive months, to further refine the design and validate the possibility to conduct future testing with them (section 4). All interviews were conducted remotely with respect to the COVID-19 regulations. At last, a pre-test was orchestrated with 25 non-autistic children to validate the possibility to use the developed VR platform in the two real-world clini-cal settings evoked above with autistic children, i.e., music therapists' and psychologists' sessions (section 5).

INITIAL DESIGN PROCESS WITH TWO MUSIC THERAPISTS

Method for the First Design Iteration

To acquire fundamental knowledge about designing for MT and children on the autism spectrum, initial design guidelines were derived from the literature. In particular, Baltaxe-Admony et al. [START_REF] Baltaxe-Admony | Exploring the creation of useful interfaces for music therapists[END_REF] investigated the reasons behind the deficiency of technology in MT by interviewing six music therapists from around the world. When inquiring about what the therapists were missing from their previous experiences with technological solutions, five design considerations emerged: 1) versatility, 2) ease to travel with, 3) easy to set up, 4) a stand-alone technology, and 5) possibility for data collection. Points 2 to 4 led to choose the Head-Mounted Display (HMD) Oculus Quest 2 for developing the application, as it is wireless, portable, and has relative ease of setting up. Point 1, versatility, was included as a discussion topic for planned interviews. Point 5, data collection, was omitted due to being irrelevant for the time being.

Building on these design guidelines, an interview with two music therapists was conducted to understand their specific needs when working with autistic children. One had a 6-year education in the MT field and 13 years of professional experience, including a diverse clientele. Her typical sessions last around 45 minutes for children and 2 hours for adults. They usually take place at the client's home, and can be individual or group sessions. The second music therapist is a professor with vast experience in researching how MT can be used to help autistic children [START_REF] Geretsegger | Common characteristics of improvisational approaches in music therapy for children with autism spectrum disorder: Developing treatment guidelines[END_REF][START_REF] Holck | Turn-taking in music therapy with children with communication disorders[END_REF]. The interview lasted about an hour. The researchers asked questions about the design of the VE, the interaction with the instruments, and the possibilities for training social and communication skills.

Findings from the Preliminary Interview

Designing the Music Activity

The music therapists first suggested making the VE familiar and simple. Thus a classroom was designed, as it is a common location for MT sessions. To make it resemble a typical classroom, items such as a bookcase, a blackboard, school lockers, and a row of school desk chairs were added to the VE.

The instruments should also be familiar while also taking advantage of VR and the ability to make elements that are otherwise not physically possible. Thus, two VR Musical Instruments (VRMIs) were created: a virtual xylophone as the familiar instrument, and The Looper as the specific VRMI (Figure 1). Their designs draw upon guidelines outlined by Serafin et al. [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF]. In particular, both natural and 'magical' interaction possibilities were added, where the xylophone was promoting natural interaction and the Looper the 'magical'. Other guidelines were considered, Figure 1. A view of the classroom. In the front, the play area with the two instruments, the Looper (left) and the xylophone (right).

such as using appropriate feedback and mapping, implementing for minimal latency, and preventing cybersickness [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF]. Last but not least, the experience had to be social, which is also often highlighted in technology-based autism research [START_REF] Parsons | Whose agenda? Who knows best? Whose voice?' Co-creating a technology research roadmap with autism stakeholders[END_REF]. To do so, the Looper was inspired by the social interaction occurring during board games. Hence, the therapist and child would both be interacting with the Looper across the table, thus prompting joint attention. At last, the therapist could construct rules such as turn-taking or other rules that can be customised to the child's needs.

The Looper consisted of an oval track with an RGB wave effect to make the instrument salient and attract the child's attention. A small black ball was looping the track, the speed of which could be controlled by adjusting a handle on the side of the Looper. When passing by one of the white dots on the track, a bass drum sound played, functioning as a backbeat. Then, the user could add cubes on the track with different sound modes. When the ball passed through the cubes, they would play a sound and provide visual feedback, consisting of a brief change in colour (white to yellow) and a simple particle system with pink sprinkles. The different sound modes were a snare drum, kick drum, crash cymbal, and a 'wobbling' sound. To support predictability, they are all indicated by fitting icons on the cubes.

To avoid cybersickness, it is advised to minimise the amount of acceleration while being mindful of the locomotion techniques available [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF]; continuous locomotion techniques were implemented for a seated experience. To that end, translation was enacted by using the left thumbstick, while a 45 • rotation was performed by moving the right thumbstick to the right and left. When initiating movement, the user would instantly reach max speed and likewise stop immediately, avoiding inducing cybersickness. Real-walking was also possible for traversing the VE.

Design of the Avatar

The representation of the player's body can influence the VRMI interaction [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF], thus the design of the avatar was discussed with respect to the autistic perception. Some studies have shown improvements in social skills when using a highly realistic-looking avatar, especially regarding the use of realistic facial expressions [START_REF] Herrero | An immersive virtual reality educational intervention on people with autism spectrum disorders (ASD) for the development of communication skills and problem solving[END_REF]. Yet, others find that the individual can struggle when too many stimuli are present, i.e., to recognize and distinguish facial expressions from one another [START_REF] Keating | Facial expression production and recognition in autism spectrum disorders[END_REF]. Moreover, when asked about the avatar design, the therapists were concerned about using a realistic avatar, being potentially intimidating. Because of the conflicting views and with the feedback from the therapists, we decided to utilise the default Normcore avatar, which is a simple iconic-looking avatar (Figure 2), to keep with our user-centered approach. The avatar had a black sphere for the head with a white, smiling mouth. The mouth changed size based on the microphone input. Remotely, the users would see other users' hands as simple mittens to reduce the amount of data needed to be sent and thus the overall latency, which also minimises the risk of cybersickness [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF]. Locally, the mittens were exchanged with two five-fingered hand models, created in Autodesk Maya. This change drew upon the VRMI interaction [START_REF] Serafin | Virtual reality musical instruments: State of the art, design principles, and future directions[END_REF] and also aimed at adding avatar-realism, to induce a higher level of perceived presence [START_REF] Roth | Avatar realism and social interaction quality in virtual reality[END_REF], and thus to increase the ecological validity of the environment that is of importance for social neuroscience.

Implementing the First Iteration

The application was developed in Unity 2019. 4.19f1, with the SteamVR plug-in and the multiplayer framework Normcore. With Normcore, the therapist and their client can connect to the same room, which is defined by an app key. For voice communication, Normcore uses a VoIP (voice over internet protocol) that is optimized for minimal latency. This feature can for instance allow the music therapist to also sing with the child during the sessions.

EVALUATION BY A MUSIC THERAPIST

This evaluation had two objectives: gathering design insights to improve the application, and validating the potential use of the application in the music therapist's sessions. The following subsections first present the method used, then the experiment's findings, and finally detail the respective design adjustments that were made.

Method for the Evaluation

A remote VR experiment was conducted with a music therapist from the preliminary interview. Without the opportunity to provide the music therapist with an HMD, the experiment was conducted via videocall, where a researcher shared their view from VR. The therapist was asked to 'puppeteer' the researcher to interact within the VE, and to vocalise her thought about what she saw, in line with the thinking aloud method [START_REF] Ericsson | Protocol Analysis: Verbal Reports as Data[END_REF]. The experiment lasted about an hour. Likewise the preliminary interview, the researchers inquired about the design, the interaction with the instruments, and the possibilities for training social and communication skills. Data were analysed with traditional coding; the feedback from the therapist was transcribed and categorised into emerging themes by three researchers [START_REF] Bjørner | Qualitative Methods for Consumer Research: The Value of the Qualitative Approach in Theory and Practice[END_REF]. The categories were compared and discussed between the researchers which led to the final categories, from where data was interpreted.

Findings from the Experiment

Three themes emerged from the data, namely, usability, social interaction, and functionality, as well as seven categories (Table 1). They are described hereafter.

THEMES CATEGORIES Usability

• Ease of use 1. Overview of the emerging themes with their definitions and related categories from the experiment with the music therapist.

Beginning with usability, the therapist found the instruments intuitive to interact with and familiar, which could be perceived as reassuring and engaging. Indeed, the xylophone was easily recognisable, and for the Looper, she said "...even if I had never seen it before, there is still something intuitive and familiar, about this table with this ball that is going around. It kind of reminds [me] of air hockey or something similar. You get an urge to approach [it] and do something with it". Furthermore, she highlighted the positive effects of the Looper's gaming-like features. Yet, concern about its versatility arose due to the idiosyncratic preferences and needs of autistic individuals, making it potentially too advanced for some children.

In terms of social interaction, what contributions each user had made was unclear, possibly hindering the perceived sense of agency. To that respect, displaying more easily distinguishable sounds was advised to better hear one's contributions. Though, she highlighted the strong social potential of the application. For instance, a simple gesture such as asking the other player for a cube that could be of reach could constitute a great exercise for training social interaction skills. At last, the therapist found the avatar design too simplistic, as only the mouth was reacting to the microphone input, which could be perceived as unsafe. Indeed, facial expressions are important during non-VR therapists' sessions to adapt their behaviour according to the child's state. However, she added still being able to read their client's body language, which is another viable method for understanding their mood, and to adjust the soundscape accordingly.

Regarding functionality she warned about potential unnecessary distractions. She specifically mentioned that stacking the cubes could take over the child's attention and be perceived as the main task, thus removing the focus from creating sounds together. Moreover, the colourful items and furniture could also grab the child's attention. Hence, the therapist proposed two solutions: using more neutral colours for the furniture or making the salient items into VRMIs. Regarding this second possibility, the lockers could produce a sound whenever opened, and musical drawings could be created by drawing on the blackboard. Furthermore, the therapist suggested to exploiting more the virtuality of the xylophone, by adding visual feedback or switching colours in line with the different soundmodes of the cubes. At last, regarding the Looper, more soundmodes were desired, as well as simplifying the backbeat and its relation to the white dots on the track more obvious.

The therapist concluded that the application would be used in their sessions with the mentioned adjustments. "There are some elements that will be lost [in VR], but what other things can we then add? It is the gestures and intuition and mood that we need to compromise because there is something other, that [VR] can do, which is interesting. And it will be exciting to find out what that is. So, it can be an extension of what you otherwise can do in the musical room". She added being excited to participate in future iterations and tests to discover how to properly use it and maybe to expand the application even more.

Redesigning the Instrument

Based on the therapist' feedback it was decided to enhance the Looper and remove the xylophone, which was considered unnecessary. To that end, brainstorming sessions were conducted between the authors. This process led to replacing the Looper's track with a railroad, as autistic children often enjoy trains [START_REF] Scheerer | Attention capture by trains and faces in children with and without autism spectrum disorder[END_REF]. Hence, a locomotive was used instead of a ball to loop over rails. Gates replaced the cubes to remove attention from stacking the objects. The gates could be placed across the rails so that the locomotive could drive through and activate the corresponding sound and additional visual effect (music notes jumping out from the gate). Authors hypothesised that these changes would make the Looper more usable and discoverable -and thus more adapted to the target group previously described by the therapist in section 3.

In addition to these changes, interaction possibilities were added to provide more control over the created soundscape. The controls are summarised in Table 2. Controllers were assembled in a control panel (see Figure 4). More distinguishable sound modes were also implemented, i.e., marimba, drums, 'magic' sounds (whistle, plings, and whooshes). The VE resulting from this redesign is displayed in Figure 3.

Controller Purpose

Other

CONTINUED DESIGN PROCESS WITH TWO PSYCHOLOGISTS

A second design iteration was conducted with two psychologists with two objectives: refining the design according to their specific needs and validating the potential use of this application in their sessions. This section will first present the method that was used, and then the design insights that emerged and led to several design adjustments.

Method for the Second Design Iteration

The psychologists are autism experts working in a day hospital and use digital tools in their daily interventions (i.e., video games with a projected screen, tablet, and robots). Also, they have previously worked with third author, and thus have experience with evaluating the use of augmented reality technologies in sessions with autistic children [START_REF] Bauer | Designing an Extended Reality Application to Expand Clinic-Based Sensory Strategies for Autistic Children Requiring Substantial Support: Participation of Practitioners[END_REF].

With their expertise and cooperation, future testing with the target group was planned (more about this in section 6.2).

For iterating the VR application, the psychologists participated in three online meetings, where the first author would share their screen to showcase the VR application.

Design Insights from the Psychologists

Similar to the music therapist's feedback (in section 3), notes were made about the avatar design and the ability to better see each others' contributions. Additional comments were made about the design of the VE, potential interaction and locomotion difficulties, audio effects, as well as the training and introduction to the system for the children. Their different insights are described hereafter.

The Avatar Design

The psychologists suggested making the avatar more expressive. Hence, we added eyes and a nose and made it possible to change the avatar colour by pressing one of the colour buttons placed on the wall. The colour allowed to better visualise what contributions each user made. When interacting with one of the gates, the flag on top of the gate changed colour corresponding to the interactor's avatar colour (Figure 5).

Adaptation to Autism Perception

To adapt to the specific autism perception, the psychologists asked to simplify the space and to avoid unnecessary distractions, similar to the music therapists. Thus, only objects meant for interaction were kept (the colour buttons, the gates, the railroad and its control panel). Then, as ASD can lead to mobility issues, the interactions were further discussed. To minimise errors while operating the instrument, big buttons and handles were suggested for the control panel. Also, the gates were given a relatively big size and mass, making sure that they would not easily tip over. Psychologists also asked that the session could be performed from a seated position. At last, paying attention to sound modes that the gates are given was deemed impor-tant, as people on the autism spectrum typically have difficulties processing sensory inputs [START_REF] Lord | Autism spectrum disorder[END_REF]. It was then advised to avoid high-pitched sounds, resulting in replacing some of the sounds with low-pitched instruments (e.g., marimba, drums, and rhodes).

Virtuality

The psychologists stressed the importance of using salient elements of virtuality, to help the children to separate the virtual from the real world. Here, the non-realistic avatar and visual effects could serve as useful signals.

Other

The psychologists suggested adding items that the children could break or throw around, as this is common in their experience and could be used for communicating. This was noted as future work. Tutorials for the VR tool were also suggested; however, it was later mentioned to be unnecessary as the therapist could guide the child in the VE.

Implementation of Second Iteration

The application was developed in Unity 2020.3.18f1 for the Oculus Quest 2. The framework used for setting up VR interaction was XR Interaction Toolkit, and Normcore was used to provide multiplayer functionality.

PRE-TESTS WITH NON-AUTISTIC CHILDREN

Pre-tests were conducted with non-autistic children to assess their acceptability, usability, and perception of the VR application, We considered that gathering positive feedback about the acceptability and usability of the application with non-autistic children could validate both of the future testing with the psychologists.

Method for the Pre-tests

A parent from author's professional network invited his child's class to visit the Multisensory Experience Lab at Aalborg University in Copenhagen. In connection with the visit, the 25 children (age 9) were recruited as proxy participants for evaluating the VR artefact. The children came in groups of 4 or 5, accompanied by their respective teachers. Each child was given about 3 minutes to explore the environment alone. They were aided to wear the HMD and asked if the image that they saw was blurred. Based on their answer, the HMD was further adjusted until the child agreed. Children were provided with guidance if they asked questions or stood still. The view from the HMD was streamed to a PC monitor so that the researcher could observe the child's behaviour in relation to their actions in VR.

During the testing, the first author took notes of the child's behaviour, interaction (ease of use), and motivation, both in real life with the HMD, and by looking at the screen. Comments from the other children were also taken into account. As the pre-test mainly aimed at evaluating the acceptability and usability when wearing the HMD, the bias created by the other children observing and commenting on the child testing the environment was considered as not having a non-significant impact.

Findings from the Observations

Findings suggested that more guidance was needed. This could be done by having a guide with them in VR or including tutorials for the different features.

The need for small adjustments to the control panel appeared; a heavier hinge joint for the lever would decrease the sensitivity of the tempo of the locomotive, and greater rotational sensitivity for the rotator, to decrease the risk of straining the wrist. The sizing of the furniture also had to be decreased, as many children found it difficult to reach some of the items on the tables. Also, to promote cooperation between the users, the size of the railroad had to be reduced so that the ends of the table could be closer. This feature has to be included for future testing with autistic children to prompt the social VR experience. Some children tried methods to 'break the system', which aligns with psychologists' views about how autistic children would interact with the application. For instance, children threw the gates around the virtual room, which seemed enjoyable to them. Others tried to exit the room, which at times resulted in the virtual player clipping through the walls of the room and in an endless fall. This did not scare the children. It was clear that prevention of clipping through the virtual walls, as well as a reset or 'clean up' button, were needed. Indeed, the alternative would be to terminate the VR experience and restart the app, which could break the flow in the session. On the technical side, the Oculus Quest 2 did not seem too heavy or uncomfortable for the children. The battery lasted for about 2 hours, which is sufficient for one or two full sessions of MT.

DISCUSSION AND FUTURE WORKS

The VR-based MT application presented in this paper is based on feedback from professionals experienced in working with children and adolescents diagnosed with ASD, thereby creating the foundation for future studies investigating its efficiency to increase the social capabilities of the target group. The application allows a child on the autism spectrum to log into an online VE without physically interacting with a music therapist, thereby reducing the risk for social anxiety. Additionally, VR enables the music therapist to access virtual instruments that are not accessible in real life and are potentially easy for an autistic child to interact with.

Adapting to the Autistic Perception

Both the music therapist and the psychologists encouraged to simplify the VE to adapt to the autism perception. More specifically, only meaningful virtual objects should be kept visible to not potentially catch the child's attention, removing focus from the social interaction.

According to the participating experts, the designed Looper instrument could potentially offer sufficient usability for an autistic child to use -with certain adjustments. Clarifying the perception of what contributions each user had made, was deemed fundamental to facilitate social interaction features (e.g., joint attention). More distinguishable sounds were suggested by the music therapist to feature as the separator of user contributions. This resulted in marimba, drums, and 'magic' sounds (whistle, plings, and whooshes) sounds. In contrast, the psychologists requested low-pitched sounds as these are more easily processed by individuals on the autism spectrum, which were, therefore, implemented for the second iteration. In future work, the sounds could be customised to their preferences and need to allow for a more versatile tool.

Concerning the avatar, all the therapists advocated for using a simplified model rather than realistic. Though, findings from a recent VR study conducted with 7 children with mild autism show improvements in social skills when using highly realistic-looking avatars [START_REF] Herrero | An immersive virtual reality educational intervention on people with autism spectrum disorders (ASD) for the development of communication skills and problem solving[END_REF]. We can hypothesize that this contrast may be due to the fact that the therapists in this paper commonly work with children with severe to moderate autism, contrary to this study's participants. This discrepancy calls for further research to evaluate if therapists' needs regarding the avatar design are correlated to autism severity.

It should be noted that there are limitations to the VR system. As mentioned by both music therapists and psychologists, facial expressions can be an important aspect of recognising the child's emotions. With body language being the alternative, as noted by the music therapist, two types of avatars could convey more expressive movements: an avatar with inverse kinematics -and a full-body avatar with additional equipment such as sensors attached to hips and feet. However, with the design consideration of using a stand-alone technology, adding equipment could be an issue, as well as possibly hinder the child's acceptance.

As the psychologists had suggested, it was found that some non-autistic children who tested the application would throw around with the virtual objects or 'break the system' by moving outside the room's boundaries. Such behaviours could indicate a strong excitement or a will to examine the limits of the system. Moreover, the psychologists noted that trying to break the system could be understood in communicative ways and could be beneficial to incorporate.

Limitations and Future Works

With the COVID-19 regulations that were enforced during the design process, neither the music therapists nor psychologists could try the VR application for themselves. Thus, additional evaluations must be conducted with the autism experts in VR before an evaluation can be conducted with autistic children.

In a previous augmented reality study [START_REF] Bauer | Designing an Extended Reality Application to Expand Clinic-Based Sensory Strategies for Autistic Children Requiring Substantial Support: Participation of Practitioners[END_REF], before experiencing the VE, the practitioners were worried of feeling enclosed within the HMD and that it would not be adapted for autistic children. However, neither the practitioners or non-autistic children mentioned this in the present study.

It should be mentioned that the application is developed by and in co-operation with non-autistic people. Although the pre-test with school children provided valuable insights, it only considered the perception of non-autistic users. Thus, the VE has not yet been tested with autistic participants and cannot account for potential hypersensitivity that some autistic children display. Especially, the choice of the audiovisual effects generated by an activated gate may receive negative feedback from children on the autism spectrum. While we do not question that practitioners could teach the children how to interact in VR, conducting tutorials with both practitioners and children could help to minimize potential risks due to hypersensitivity. Indeed, it could gradually allow them to get used to the VE or to individualize the VE based on their perception.

Previous work show that VR can prompt social interaction [START_REF] Provenzano | Music therapy for communication in children with autism spectrum disorder[END_REF][START_REF] Adjorlu | Virtual reality music intervention to reduce social anxiety in adolescents diagnosed with autism spectrum disorder[END_REF][START_REF] Gal | Using Innovative Technologies as Therapeutic and Educational Tools for Children with Autism Spectrum Disorder[END_REF][START_REF] Geretsegger | Music therapy for people with autism spectrum disorder[END_REF], yet question remains about the ecological validity of VR interventions. As MT is time consuming and thus require months or years before noticeable results are showing [START_REF] Provenzano | Music therapy for communication in children with autism spectrum disorder[END_REF][START_REF] Holck | Turn-taking in music therapy with children with communication disorders[END_REF], longitudinal studies are necessary to evaluate this question.

This paper focused on designing a multiplayer VR tool to meet the needs of some primary users, i.e., music therapists and psychologists. Future focus will be on whether they can promote social and communications skills by adding the tool in common autism interventions. To that end, the VR application will be evaluated at the day hospital in collaboration with the two psychologists, with six children (+11 years) with severe to moderate ASD. The children will do a 20-minute session once a week over several weeks to assess their acceptability, usability, and the evolution of the social interaction.

Figure 2 .

 2 Figure 2. The default Normcore avatar used to represent the users in the VE.

Figure 3 .

 3 Figure 3. The VE and the interaction stations. Top left to right: the gates, the avatar, and colour buttons. Bottom: the railroad system with control panel on the side.

Figure 4 .

 4 Figure 4. The control panel for the railroad system. From left to right; lever, +/-buttons, rotator, and whistle.

Figure 5 .

 5 Figure 5. The flags on the gates change colours depending on the colour of the player who last interacted with it. Also, to the left; the revised avatar design in red.

Table 2 .

 2 feedback Controllers' functions and related feedback.

	Lever	Train drives	-
		faster/slower.
	+/-buttons Volume of the	Transparency of the
		gate sounds is de-	smoke is
		creased/increased.	decreased/increased.
	Rotator	Pitch of the	Size of the
		gate sounds is de-	smoke is
		creased/increased.	increased/decreased.
	Whistle	Whistles and the	Smoke colour
		train makes a	changes to one of
		horn sound.	the avatar colours.

Acknowledgments

We would like to thank Professor in Music Therapy Ulla Holck and Music Therapist Anne Cathrine Hulthin Andersen for the great guidance, that shaped this study. We are grateful for the advice and feedback provided by psychologist and researcher Olivier Duris, clinical psychologist and Ph. D. student Charlotte Labossière, and psychiatrist and physician director Marie-Noëlle Clément at the Association CEREP-PHYMENTIN, Day hospital André Boulloche. Funding Information: The participation to the conference was supported by the European Art Science and Tech-nology Network (EASTN-DC).


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Storing the declaration of human rights on one data DNA molecule

scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

-84,8% "Payload": encoded data.

-7,2% "Overhangs": 9 specific 3' overhangs of 4nt.

-8,0% "PCR primers": block amplification + add specific 3' boverhangs through BsaI restriction sites.

*

  community consensus to store information on DNA is to use short single strand DNA (ssDNA) molecules. This approach has some limitations: encoding constraint, DNA stability, recovering DNA, sequencing technology, etc. To overcome them, we chose to store information on long double-strand DNA (dsDNA) molecules. raw signal (fast5) Basecalling: converting files in DNA sequence (fastq) -Read length: up to 1Mb -Acccuracy: 99% -Real time sequencing -Portable -Similar cost to Illumina sequencing -In progress: real-time selective sequencing and f detection of chemical modification DNA SEQUENCING -Chemical synthesis by phosphoramidite method -High cost: 0,123€/base -Oligonucleotide length: 350nt -Error rate: negligible -Synthesis speed: 100 to 200 seconds/nucleotide -In development: enzymatic synthesis SEQUENCE DESIGN In vitro: DNA molecules are simply stored at room temperature in a buffer (Storage density: DNA molecules/mm . ° Random access: access to a specific file without decoding the entire storage. ** Duplication: create complete copy of DNA storage.

  = digestion + ligation + PCR (10 hours) Phase 2 concatenation = digestion + ligation + PCR (10 hours) Phase 1 concatenation = phosphorylation + dimerization + digestion + ligation + PCR (16 hours) Build 500bp dsDNA block with ssDNA oligonucleotides:


Davinia Moreno
email: davinia.moreno@cenieh.es

Ana Isabel Ortega

Christophe Falguères

Qingfeng Shao

Olivier Tombret

Asier Gómez-Olivencia

Arantza Aranburu

Francois Trompier

José María Bermúdez De Castro

Eudald Carbonell

François Trompier

Juan Luis Arsuaga

ESR/U-series chronology of the Neanderthal occupation layers at Galería de las Estatuas (Sierra de Atapuerca, Spain)

Keywords: ESR/U-series dating, Neanderthal, Late Pleistocene, Atapuerca site complex, Iberian Peninsula

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The karst system of the Sierra de Atapuerca is well known for its Lower (Gran Dolina and Sima del Elefante) to Middle (Gran Dolina, Galería and Sima de los Huesos) Pleistocene and Holocene (Cueva del Mirador, Galería del Sílex and Portalón) paleoanthropological record [START_REF] Apellániz | Los materiales de superficie del santuario de la Galería del Sílex[END_REF]Carbonell et al., 2014). However, for a long time, no Upper Pleistocene chronologies were found in the caves, and the presence of Neanderthal groups in the Sierra de Atapuerca was restricted to several open-air archaeological sites (Navazo and Carbonell, 2014) such as Hotel California (Arnold et al., 2013), Hundidero (Navazo et al., 2011), Valle de las Orquídeas (Mosquera et al., 2007) or Fuente Mudarra (Santamaría et al., 2021), among others.

The Galería de las Estatuas (GE) site, located in the upper level of the multilevel Torcas system, within the Cueva Mayor -Cueva del Silo complex (Ortega, 2009), revealed an Upper Pleistocene detrital sequence sealed by a speleothem (Aranburu et al., 2012;Arsuaga et al., 2017) in which the first Neanderthal fossil (a foot phalanx) in the Atapuerca karst system was found (Pablos et al., 2019), along with stone artifacts of clear Mousterian affinity as well as other palaeontological remains (Arsuaga et al., 2017). Furthermore, this site has also provided Neanderthal mitochondrial and nuclear DNA extracted from sediments which shows a population replacement in northern Iberia c. 100 ka BP (Vernot et al., 2021). Therefore, this site contains insights about Neanderthal occupations, subsistence strategies and population dynamics in the more inland Iberian Peninsula and completes the gap of Upper Pleistocene chronologies at the Sierra de Atapuerca karst system (Arsuaga et al., 2017;Vernot et al., 2021).

Most of the Neanderthal sites in the area surrounding the Sierra de Atapuerca are chronologically within MIS 3 -4 periods with the exception of Fuente Mudarra site recently dated by OSL to MIS 3 -5 (Santamaría et al., 2021). Inside the karst system, Galería de las Estatuas is the first archaeological site to be dated to MIS 4 -5 using single-grain TT-OSL and OSL dating (Demuro et al., 2019). Taking into account the importance of this site within the entire Atapuerca karst system for understanding the time when the Neanderthal groups occupied the caves, a new chronological study was designed to further constrain the age of the Galería de las Estatuas site. The main aim of this study is to get the first ESR/U-series ages by dating several fossil teeth and provide a solid multiproxy and multi method dating approach for the stratigraphical sequence of both, GE-I and GE-II, test pits.

The Galería de las Estatuas (GE) site

The GE site is located in the upper level of the Torcas multilevel system (Cueva Mayor-Cueva del Silo complex), a sub-horizontal passage of about 615 m long, 10 m in width and 15 m in height, situated at +88 m above the current Arlanzón river (Ortega et al., 2013) (Fig. 1). It has been excavated since 2008 to present through two test pits called GE-I (ca. 9 m 2 ) and GE-II (ca. 6 m 2 ), revealing an Upper Pleistocene detrital stratigraphic sequence of, at least, 5 and 2 lithostratigraphic units (LUs) in GE-I and GE-II test pits, respectively (Aranburu et al., 2012) (Fig. 2). It has been interpreted as an ancient entrance to the cave system that has been sealed by a stalagmitic flowstone (Arsuaga et al., 2017).

The five LUs have yielded a large number of lithic artefacts exhibiting clear Mousterian affinities and a rich assemblage of faunal remains dominated by equids and cervids (Arsuaga et al., 2017). Additionally, a human foot phalanx of clear Neanderthal affinities was found in the interface between LU-3 and LU-4 in the GE-I test pit (Pablos et al., 2019) and both pits have yielded evidence of Neanderthal ancient DNA (both nuclear and mitochondrial). Finally, the pollen analysis of the stratigraphical sequence also provided information regarding the paleoecological changes occurred in the Sierra de Atapuerca during MIS 4 -5 (Arsuaga et al., 2017;Demuro et al., 2019) Fig. 1. Approx. here

Previous chronological framework

The first attempt to date the GE site was carried out by applying radiocarbon dating ( 14 C) on faunal remains from levels LU-1 and LU-3. A series of eight ages were obtained ranging from 43.5 to > 46.3 14 C ka BP (uncalibrated) but all these ages were close to the analytical limits of the technique and were cautiously interpreted as minimum ages (Arsuaga et al., 2017). A first U-series age of 13.7 ± 0.4 ka cal BP was obtained for the stalagmitic flowstone sealing the detrital sequence in GE-I and a second date from the base of the speleothem at GE-II yielded an age of 53.7 ± 3.5 ka BP (Martínez-Pillado et al., 2014;Vernot et al., 2021).

Single-grain Optically Stimulated Luminescence (OSL) dating was also applied with the aim of better constrain the age of GE and seven samples were collected for this purpose: five from GE-I and two from GE-II. These single-grain OSL ages suggested that the sediment sequence excavated in GE-I test pit accumulated, at least, between 80-112 ka in GE-I and between 70-79 ka in GE-II. Replicate Thermally Transferred OSL (TT-OSL) single-grain ages were calculated and yielded results in agreement with the OSL chronologies at 2σ for three of the four samples investigated, although in all cases the TT-OSL ages were systematically older than their single-grain counterparts (GE-I: 123 ± 10 ka in LU-2 and 126 ± 14 ka in LU-4; GE-II: 86 ± 8 ka in LU-1 and 84 ± 7 ka in LU-2). These ages place the sedimentary sequence of GE-I within MIS 5 and the GE-II pit within late MIS 5 and early MIS 4 (Demuro et al., 2019). SM-2 in Supplementary Material) were collected from levels LU-2 to LU-5 of the GE-I test pit while two teeth (GE1808 and GE1809) were found at level LU-2 of the GE-II test pit (Table SM-2 in Supplementary Material).

Sample preparation

Teeth were prepared at the Muséum national d'Histoire naturelle (MNHN) of Paris (France) (Fig. SM-1 in Supplementary Material). Dental tissues (enamel, dentine and cementum) were mechanically separated and cleaned with an electric drill. In order to eliminate the effect of external α particles, a minimum thickness of 30-50 µm was removed from both, inner and outer, sides of the enamel fragments (Table SM-1 in Supplementary Material). Then, a part of the enamel was ground and sieved and two different granulometric fractions were collected. The 100-200 µm fraction was used for ESR measurements. The rest of the powder was employed for U-series analyses.

ESR analyses

The 100-200 µm grain-size clean enamel fraction of each tooth was split into 10 aliquots and 9 of them were irradiated with increasing doses (5,10,20,40,80,160,320, 640 and 1300 Gy) using a 137 Cs Gammacell gamma source at the Centro Nacional de Investigación sobre la Evolución Humana (CENIEH) in Burgos (Spain). ESR measurements were performed at room temperature at the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) in Fontenay-aux-Roses (France) with an Elexsys E500 X-band spectrometer using the following parameters: 1 mW microwave power, 1024 points resolution, 100 kHz modulation frequency, 0.1 mT modulation amplitude, 20.48 ms conversion time, 5.12 ms time constant, 120 G sweep width and 6 scans. Furthermore, data reproducibility was checked by running ESR measurements repeatedly during four different days. ESR intensities were extracted from peak-to-peak amplitude measurements between T1 and B2 peaks at g=2.0018 (Grün et al., 2008). The Equivalent Doses (DE) were calculated with the Microcal Origin 8.5 software using a Single Saturating Exponential (SSE) (Fig. SM-2 in Supplementary Material) function (Yokoyama et al., 1985). The irradiated point at 320 Gy was systematically underestimated showing the samples did not receive the expected dose. So, we decided to subtract this point for all the samples allowing to avoid an overestimation of the DE.

U-Th analyses

The dental tissues (enamel and a part of cement) were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) at Musée de l'Homme in Paris (France), using a Thermo-Electron iCAP-RQ quadripole mass spectrometer and following the procedure described in Douville et al. (2010). The chemical protocol is explained in Richard et al. (2015). The dentine tissues and the rest of cement samples were analyzed by a Multicollector Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS) at Nanjing Normal University in Nanjing (China) following a protocol similar to that explained in Shao et al. (2019). The main steps consist in adding a 233 U-236 U-229 Th spike to the dissolved sample. U and Th are then separated and purified on UTEVA resin columns. Distilled and clean nitric and hydrochloric acids were used according to each step. The U and Th fractions are eventually pre-analyzed in order to prepare the adapted final dilutions for the best measurements, either on Q-ICPMS or MC-ICPMS. An uraninite (HU-1) standard with spike, in secular radioactive equilibrium, is analyzed regularly for instrument control.

The total blank chemistry values must be as low as possible and the internal standard sample values after application of the various corrections must be corrected to validate the ages. Ages were calculated using half-lives of 75,584 years for 230 Th and 245,620 years for 234 U (Cheng et al., 2013). All errors are reported at 95% confidence level.

Dose rate evaluation

The Dose Rate (D) was obtained from the sum of the α-, β-, γ-and cosmic-ray contributions. As teeth were handed over after the excavation campaigns and because most of the layers were excavated and disappeared, no in situ measurements of the natural radioactivity of the sediment could be made except for sample GE1802. This single in situ measurement was carried out using a NaI(Tl) probe connected to an Inspector 1000 multichannel analyser (Canberra) and the dose rate (115 ± 50 µGy/a) was calculated using the "threshold approach" (Mercier and Falguères, 2007). External ß contributions were assessed from the radioelement content (U, Th and K) determined by high resolution low background gamma-ray spectrometry (HRGS) at the Centro Nacional de Investigación sobre la Evolución Humana (CENIEH) in Burgos (Spain). The cosmic dose rate was estimated according to the depth of the sediments, the thickness of the limestone roof, and taking into account the altitude and latitude using the formula of Prescott and Hutton (1994).

Results and discussion

ESR/U-series ages were calculated using the DATA software (Grün, 2009) except for GE1803 which was calculated using the US-ESR program allowing a slight uranium leaching in the tissues (Shao et al., 2014). Seven of the nine teeth analysed have yielded modelled ages and are presented in Table 1 andFig 2. Table 1. Approx. here Equivalent Doses (DE) are homogeneous and range between 27 ± 5 and 43 ± 5 Gy for samples from the GE-I test pit. The DE obtained for the only sample from the GE-II test pit that could be analyzed is slightly higher (52 ± 4 Gy). The external dose rate due to the surrounding sediment is preponderant in the total Dose Rate (D): between 87% and 96% for GE-I teeth, reaching 98% for GE1808 in GE-II. 238 U content in enamel is very low and ranges between 0.013 ± 0.001 to 0.070 ± 0.002 ppm excepting for GE1804 and GE1806 which contain 5 to 10 times more. The U-content in dentine is higher, ranging from 0.313 ± 0.001 to 1.063 ± 0.001 ppm while cement is the tissue with the highest U-content, ranging from 0.735 ± 0.001 to 17.86 ± 0.63 ppm.

The difficulties to obtain reliable and accurate ages from the fossil teeth of the Galería de las Estatuas site come from two main reasons. Firstly, teeth have low U-content in enamel and the limits of U-series measurements by ICPQMS are reached. Although it was technically possible to calculate US-ESR ages, the obtained p-values show a large error range (Table 1).

GE1804 probably acquired post-burial uranium very late, at the beginning of the Holocene period as suggested by positive p-values higher than seven obtained for the three tissues.

Secondly, the heterogeneity of the layers renders difficult the measurement and the evaluation of the external dose rate which represents more than 80% of the total Dose Rate and for some samples, almost 100%. For example, sample GE1801 (276 ± 21 ka) has provided an older age than expected and an external dose rate twice lower than for others samples. The LU-5, where GE1801 was found, has been described as the result of the degradation of an underlying speleothem and shows a highly carbonated composition (Arsuaga et al., 2017). The difficulty of assessing the external dose rate in this highly carbonate layer coupled with the low U-content in the enamel could be likely explain this older age. It is difficult to further refine this age and it should be used with caution to make interpretations on this sequence.

The results obtained in the GE-I test pit suggest that the analyzed teeth are contemporaneous with MIS 5 ranging between 92 ± 6 ka and 104 ± 6 ka for LU-5 to LU-2.

These ages are in accordance with the single-grain OSL ages suggesting that the sediment sequence and archaeological remains excavated in GE-I may have been accumulated 80-112 ka. In the GE-II test pit, the ESR/U-series age obtained (115 ± 18 ka) is slightly older than that proposed by single-grain TT-OSL which were deposited 70-79 ka.

Conclusions

The Galería de las Estatuas site is the first site within the Sierra de Atapuerca to provide Neanderthal human fossil in a well-established stratigraphic context (Pablos et al., 2019), as well as Neanderthal DNA extracted from sediments (Vernot et al., 2021). The single-grain OSL and TT-OSL ages obtained for the two test pits excavated since 2008 revealed an age for GE-I to approximately 80-112 ka and 70-79 ka por GE-II suggesting that the GE site is one of the oldest Neanderthal sites (MIS 5) in the Iberian Peninsula (Demuro et al., 2019).

Therefore, the importance of this site highlights the need to contrast the previous dates with others obtained with a different methodology in order to verify and refine the age of this site. In that regard, nine fossil teeth were sampled in GE to be dated by combined ESR/Useries dating method: seven teeth from GE-I and two teeth from GE-II.

In GE-I test pit, six out of the seven teeth analysed provided model ages. The results for GE-I suggest that teeth are contemporaneous with MIS 5 ranging between 92 and 104 ka for LU-5 to LU-2. The older age obtained for GE1801 (LU-5 from GE-I) should be used with caution for interpretations of this sequence. The heterogeneity of the layer and the high carbonate content rendering difficult the measurement of the external dose rate seems to explain the older age obtained.

In GE-II test pit, only one of the two teeth analysed has provided a model age. The sample GE1808 has provided an age of 115 ± 18 ka which is slightly older than the singlegrain TT-OSL (86 ± 8 ka in LU-1 and 84 ± 7 ka in LU-2) ages obtained by Demuro et al. (2019).

Most of the ESR/U-series ages obtained in this work are in agreement with the previous single-grain OSL and TT-OSL ages and confirm the Upper Pleistocene age of the Galería de las Estatuas site within late MIS 5 and early MIS 4. 9,133 ± 0,002 29 ± 2 317 ± 60 3 ± 2 320 ± 60 9,79 ± 0,72 9,00 ± 0,67 7,04 ± 0,55 104 ± 6 GE1805 3 0,066 ± 0,002 0,850 ± 0,001 3,836 ± 0,002 36 ± 3 220 ± 61 6 ± 3 226 ± 61 1,18 ± 0,18 1,43 ± 0,20 1,18 ± 0,18 179 ± 11 GE1803 * 4 0,070 ± 0,002 0,4 4,344 ± 0,13 31 ± 4 317 ± 60 64 ± 50 381 ± 134 -0,17 ± 0,57 -0,02 ± 0,05 -0,02 ± 0,05 95 ± 33 GE1802 4 0,013 ± 0,001 0,313 ± 0,001 1,236 ± 0,04 27 ± 5 317 ± 60 3 ± 3 320 ± 63 -0,89 ± 0,06 0,51 ± 0,15 0,29 ± 0,14 92 ± 6 GE1801 5 0,032 ± 0,001 0,423 ± 0,001 4,167 ±0,001 31 ± 5 110 ± 41 0 110 ± 41 -0,88 ± 0,04 6,15 ± 0,59 0,58 ± 0,16 276 ± 21 GE-II GE1808 2 0,040 ± 0,001 0,856 ± 0,001 0,735 ± 0,001 52 ± 4 508 ± 72 6 ± 3 514 ± 84 -0,19 ± 0,24 1,59 ± 0,53 0,92 ± 0,42 115 ± 18

Acknowledgments

FigNine

  Fig. 2. Approx. here

FIGURESFig. 1 .

 1 FIGURES

Fig 2 . 1 .

 21 Fig 2. Location of the ESR/U-series ages in relationship with the OSL and U-Th ages in the stratigraphical profiles from GE-I and GE-II (modified from Vernot et al. (2021).

Author contributions

DM, CF and AIO designed the study; AGO and AA provided general and stratigraphic background about the site; DM and CF performed the in situ measurements and collected data in the site; DM, CF, OT, QS, AIO and FT carried out the geochronological analysis; JLA, JMBC, EC and DM provided scientific support and resources from PGC2018-093925-B-C31, PGC2018-093925-B-C32, PGC2018-093925-B-C33 and CAS18/00404; DM wrote the paper with inputs from the others.