Online consultations in mental healthcare: Modelling determinants of use and experience based on an international survey study at the onset of the pandemic.

Introduction: While online consultations have shown promise to be a means for the effective delivery of high-quality mental healthcare and the first implementations of these digital therapeutic contacts go back nearly two decades, uptake has remained limited over the years. The onset of the COVID-19 pandemic dramatically altered this relative standstill and created a unique turning point, with a massive amount of both professionals and clients having first hands-on experiences with technology in mental healthcare. Objective: The current study aimed to document the uptake of online consultations and explore if specific characteristics of mental health professionals across and beyond Europe could predict this. Methods: An international survey was designed to assess mental health professionals' (initial) experiences with online consultations at the onset of the pandemic: their willingness to make use of them and their prior and current experiences, alongside several personal characteristics. Logistic mixed-effects models were used to identify predictors of the use of online consultations, personal experience with this modality, and the sense of telepresence. Results: A total of 9115 healthcare professionals from 73 countries participated of which about two-thirds used online consultations during the initial COVID-19 outbreak. The current study identifies multiple determinants relating to the use and experience of online consultations, including the professionals' age, experience with the technology before the outbreak, the professional context, and training. Conclusions: Despite strong evidence supporting the relevance of training in digital mental health, this is clearly still lacking. Nevertheless, the COVID-19 pandemic presented a first, and potentially transformative, experience with online consultations for many healthcare professionals. The insights from this study can help support professionals and, importantly, (mental) healthcare organisations to create optimal circumstances for selective and high-quality continued use of online consultations.

Effects of single- and multiple-dose oxytocin treatment on amygdala low-frequency BOLD fluctuations and BOLD spectral dynamics in autism.

Prior neuroimaging clinical trials investigating the neural effects of intranasal administration of the neuropeptide oxytocin demonstrated a key role of the amygdala in oxytocin's neuromodulatory effects. These studies mostly demonstrated the acute effects of single-dose administrations, examining task-dependent effects of oxytocin on brain activity elicited during explicit experimental tasks or stimuli presentations. The increased consideration of oxytocin as a potential ameliorating treatment in autism spectrum disorder (ASD) requires a better understanding of how multiple-dose oxytocin administration affects intrinsic, task-free, amygdala function. In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment. Effects were assessed either after a single-dose administration, consisting of 24 international units, or after multiple-dose treatment, consisting of 4 weeks of once-daily nasal spray administrations. Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations) and modulated cross-frequency interactions between adjacent BOLD frequency components. The right amygdala showed a pattern of reduced cross-frequency harmonicity, while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment. Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment. Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin's anxiolytic, stress-reducing neuromodulatory role. The observed effects of oxytocin on amygdalar BOLD spectral characteristics and associated behaviors contribute to a deeper mechanistic understanding of the intrinsic, task-free neuromodulatory dynamics that underlie single- and multiple-dose oxytocin treatment in ASD. European Clinical Trial Registry (Eudract 2014-000586-45).

Virtual Reality for Distraction and Relaxation in a Pediatric Hospital Setting: An Interventional Study With a Mixed-Methods Design.

Accumulating evidence supports the use of virtual reality (VR) as an effective pain and anxiety management tool for pediatric patients during specific medical procedures in dedicated patient groups. However, VR is still not widely adopted in everyday clinical practice. Feasibility and acceptability measures of clinicians' experiences are often missing in studies, thereby omitting an important stakeholder in VR use in a clinical setting. Therefore, the aim of this mixed-methods study was to investigate the feasibility, acceptability, tolerability (primary outcomes), and preliminary effectiveness (secondary outcome) of Relaxation-VR in both pediatric patients aged 4-16 years and clinicians. Relaxation-VR is a VR application prototype aimed to provide distraction and relaxation for a variety of patient populations and procedures and is used to reduce anxiety, stress (tension) and pain for children in hospital. Multiple measures of acceptability, feasibility and tolerability, and pre-to-post changes in measures of pain, anxiety, stress and happiness were assessed in pediatric patients. At the end of the study, acceptability and feasibility of VR use was assessed in clinicians. Results indicate that VR use (in particular, the Relaxation-VR prototype) for both distraction and relaxation is acceptable, feasible and tolerable for a variety of pediatric patients aged 4-16 years, as assessed in both patients and clinicians, and can reduce anxiety, pain and tension (stress), and increase happiness in a hospital setting.

Rehabilitation Supported by Technology: Protocol for an International Cocreation and User Experience Study.

BACKGROUND: Living labs in the health and well-being domain have become increasingly common over the past decade but vary in available infrastructure, implemented study designs, and outcome measures. The Horizon 2020 Project Virtual Health and Wellbeing Living Lab Infrastructure aims to harmonize living lab procedures and open living lab infrastructures to facilitate and promote research activities in the health and well-being domain in Europe and beyond. This protocol will describe the design of a joint research activity, focusing on the use of innovative technology for both rehabilitation interventions and data collection in a rehabilitation context. OBJECTIVE: With this joint research activity, this study primarily aims to gain insight into each living lab's infrastructure and procedures to harmonize health and well-being living lab procedures and infrastructures in Europe and beyond, particularly in the context of rehabilitation. Secondarily, this study aims to investigate the potential of innovative technologies for rehabilitation through living lab methodologies. METHODS: This study has a mixed methods design comprising multiple phases. There are two main phases of data collection: cocreation (phase 1) and small-scale pilot studies (phase 2), which are preceded by a preliminary harmonization of procedures among the different international living labs. An intermediate phase further allows the implementation of minor adjustments to the intervention or protocol depending on the input that was obtained in the cocreation phase. A total of 6 small-scale pilot studies using innovative technologies for intervention or data collection will be performed across 4 countries. The target study sample comprises patients with stroke and older adults with mild cognitive impairment. The third and final phases involve Delphi procedures to reach a consensus on harmonized procedures and protocols. RESULTS: Phase 1 data collection will begin in March 2022, and phase 2 data collection will begin in June 2022. Results will include the output of the cocreation sessions, small-scale pilot studies, and advice on harmonizing procedures and protocols for health and well-being living labs focusing on rehabilitation. CONCLUSIONS: The knowledge gained by the execution of this research will lead to harmonized procedures and protocols in a rehabilitation context for health and well-being living labs in Europe and beyond. In addition to the harmonized procedures and protocols in rehabilitation, we will also be able to provide new insights for improving the implementation of innovative technologies in rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34537.

Cocreating a Harmonized Living Lab for Big Data-Driven Hybrid Persona Development: Protocol for Cocreating, Testing, and Seeking Consensus.

BACKGROUND: Living Labs are user-centered, open innovation ecosystems based on a systematic user cocreation approach, which integrates research and innovation processes in real-life communities and settings. The Horizon 2020 Project VITALISE (Virtual Health and Wellbeing Living Lab Infrastructure) unites 19 partners across 11 countries. The project aims to harmonize Living Lab procedures and enable effective and convenient transnational and virtual access to key European health and well-being research infrastructures, which are governed by Living Labs. The VITALISE consortium will conduct joint research activities in the fields included in the care pathway of patients: rehabilitation, transitional care, and everyday living environments for older adults. This protocol focuses on health and well-being research in everyday living environments. OBJECTIVE: The main aim of this study is to cocreate and test a harmonized research protocol for developing big data-driven hybrid persona, which are hypothetical user archetypes created to represent a user community. In addition, the use and applicability of innovative technologies will be investigated in the context of various everyday living and Living Lab environments. METHODS: In phase 1, surveys and structured interviews will be used to identify the most suitable Living Lab methods, tools, and instruments for health-related research among VITALISE project Living Labs (N=10). A series of web-based cocreation workshops and iterative cowriting processes will be applied to define the initial protocols. In phase 2, five small-scale case studies will be conducted to test the cocreated research protocols in various real-life everyday living settings and Living Lab infrastructures. In phase 3, a cross-case analysis grounded on semistructured interviews will be conducted to identify the challenges and benefits of using the proposed research protocols. Furthermore, a series of cocreation workshops and the consensus seeking Delphi study process will be conducted in parallel to cocreate and validate the acceptance of the defined harmonized research protocols among wider Living Lab communities. RESULTS: As of September 30, 2021, project deliverables Ethics and safety manual and Living lab standard version 1 have been submitted to the European Commission review process. The study will be finished by March 2024. CONCLUSIONS: The outcome of this research will lead to harmonized procedures and protocols in the context of big data-driven hybrid persona development among health and well-being Living Labs in Europe and beyond. Harmonized protocols enable Living Labs to exploit similar research protocols, devices, hardware, and software for interventions and complex data collection purposes. Economies of scale and improved use of resources will speed up and improve research quality and offer novel possibilities for open data sharing, multidisciplinary research, and comparative studies beyond current practices. Case studies will also provide novel insights for implementing innovative technologies in the context of everyday Living Lab research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34567.

Online consultations in mental healthcare during the COVID-19 outbreak: An international survey study on professionals' motivations and perceived barriers.

INTRODUCTION: While the general uptake of e-mental health interventions remained low over the past years, physical distancing and lockdown measures relating to the COVID-19 pandemic created a need and demand for online consultations in only a matter of weeks. OBJECTIVE: This study investigates the uptake of online consultations provided by mental health professionals during lockdown measures in the first wave of the COVID-19 pandemic in the participating countries, with a specific focus on professionals' motivations and perceived barriers regarding online consultations. METHODS: An online survey on the use of online consultations was set up in March 2020. The Unified Theory of Acceptance and Use of Technology (UTAUT) guided the deductive qualitative analysis of the results. RESULTS: In total, 2082 mental health professionals from Austria, Belgium, Cyprus, France, Germany, Italy, Lebanon, Lithuania, the Netherlands, Norway, Portugal, Spain, and Sweden were included. The results showed a high uptake of online consultations during the COVID-19 pandemic but limited previous training on this topic undergone by mental health professionals. Most professionals reported positive experiences with online consultations, but concerns about the performance of online consultations in a mental health context (e.g., in terms of relational aspects) and practical considerations (e.g., relating to privacy and security of software) appear to be major barriers that hinder implementation. CONCLUSIONS: This study provides an overview of the mental health professionals' actual needs and concerns regarding the use of online consultations in order to highlight areas of possible intervention and allow the implementation of necessary governmental, educational, and instrumental support so that online consultations can become a feasible and stable option in mental healthcare.

Dropping the E: The potential for integrating e-mental health in psychotherapy.

E-mental health, or the use of technology in mental healthcare, has been the focus of research for over two decades. Over that period, the evidence base for the potential of technology to improve psychotherapeutic practice has grown steadily. This sharply contrasts with the actual use of e-mental health by psychotherapists, which has remained limited. In this article, we aim to illustrate how and when different technological tools and applications can play a role in psychotherapy. At the same time, we also highlight current limitations and discuss challenges for future research. A specific, yet hypothetical case, is used to guide this narrative review and make proposed applications tangible and concrete.

Changes in endogenous oxytocin levels after intranasal oxytocin treatment in adult men with autism: An exploratory study with long-term follow-up.

Intranasal administration of the neuropeptide oxytocin (OT) is increasingly explored as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD). Previously, interactions of exogenously administered OT with its endogenous production have been demonstrated following single-dose administrations. However, the impact of repeated, long-term OT use on endogenous salivary OT levels is unknown. In this double-blind, randomized, placebo-controlled study with between-subject design, 34 adult men with ASD were either assigned to a four-week treatment of once-daily intranasal OT administrations (24 IU) or placebo. Salivary OT samples were obtained before and after the treatment period as well as at two follow-up sessions, four weeks and one year after cessation of the treatment. Receiving OT intranasally but not placebo reliably increased endogenous salivary levels of OT immediately post-treatment and at the follow-up session four weeks post treatment, indicating an interaction between exogenously administered OT and its endogenous production. Notably, increases in salivary OT at the four-week follow-up session were most pronounced in individuals with larger behavioral improvements in ASD social symptoms. These results suggest that OT's positive effects on social behaviors may lead to a self-perpetuating elevation of OT levels through a feed-forward triggering of its own release. Together, the current investigation provides initial evidence that repeated intranasal administration of OT can induce long-lasting changes in endogenous salivary OT levels, presumably through a positive spiral of OT release.

Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up.

Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.

Oxytocin induces long-lasting adaptations within amygdala circuitry in autism: a treatment-mechanism study with randomized placebo-controlled design.

Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly explored as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD). To date, however, the impact of multiple-dose IN-OT treatment on human neural circuitry is largely unknown, and also the possibility that long-term IN-OT use may induce long-lasting neural adaptations remains unexplored. Using a double-blind, randomized, placebo-controlled, between-subject design (including 38 adult men with ASD), this treatment-mechanism study showed that 4 weeks of daily oxytocin administration (24 IU/day) significantly altered intrinsic (resting-state fMRI) functional connectivity of the amygdala to core regions of the "social brain" (particularly orbitofrontal cortex and superior temporal sulcus) up to 4 weeks and 1 year post treatment. The neural adaptations in functional coupling of the amygdala to the orbitofrontal cortex were associated with reduced feelings of avoidance toward others and-at the trend level-reduced repetitive behaviors. These observations contribute to a deeper mechanistic understanding of the neural substrates that underlie behavioral effects of multiple-dose IN-OT treatment, and provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala circuitry. Future studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural circuitry and its behavioral consequences.

Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up.

Background: Intranasal administration of the "prosocial" neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects, are currently lacking. Methods: Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of 4 weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after 4 weeks of treatment (approximately 24 h after the last nasal spray administration), and at two follow-up sessions, 4 weeks and 1 year post-treatment. Results: No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social Responsiveness Scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p = .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p = .19). Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors (p = .04) and reduced feelings of avoidance toward others (p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of "vigor" (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03). Conclusions: While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further. Trial registration: The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE).

Amygdala-Hippocampal Connectivity Is Associated With Endogenous Levels of Oxytocin and Can Be Altered by Exogenously Administered Oxytocin in Adults With Autism.

BACKGROUND: Oxytocin (OT) plays a pivotal role in interpersonal bonding, affiliation, and trust, and its intranasal administration is increasingly considered as a potential treatment for autism spectrum disorder. METHODS: We explored whether variations in endogenous salivary OT concentration are related to interindividual differences in core autism symptoms and expressions of attachment in 38 male adults with autism spectrum disorder. Further, resting-state functional magnetic resonance imaging was adopted to specifically explore whether interindividual differences are reflected in the intrinsic network organization of key regions of the central oxytocinergic system. RESULTS: Positive correlations were identified between peripheral OT and expressions of secure attachment (the State Adult Attachment Measure and the Inventory of Peer Attachment), but no significant relationships were identified with scales assessing core autism symptom domains (the Social Responsiveness Scale and the Repetitive Behavior Scale). At the neural level, higher levels of endogenous OT were associated with lower degrees of interregional functional coupling between the amygdala and hippocampal regions. Interestingly, a single dose of exogenously administered OT induced a further reduction in amygdala-hippocampal connectivity, indicating that a higher availability of OT can alter the degree of amygdala-hippocampal connectivity. CONCLUSIONS: The identified associations between the oxytocinergic system, expressions of secure attachment, and amygdala-hippocampal pathways are anticipated to be of relevance for understanding the role of OT in modulating appropriate neural and physiological responses to stress and restoring homeostasis.

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II.

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.

Long-term oxytocin administration enhances the experience of attachment.

The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that a single-dose of exogenously administered OT can affect trust and feelings of attachment insecurity. With the present study, we explored the effects of two weeks of daily OT administration on measures of state and trait attachment using a double-blind between-subjects randomized placebo-controlled design. In 40 healthy young adult men state and trait attachment were assessed before and after two weeks of daily intranasal OT (24 IU) or placebo using the State Adult Attachment Scale and the Inventory of Parent and Peer Attachment. Mood, social responsiveness and quality of life were additionally assessed as secondary outcome measures. Reductions in attachment avoidance and increases in reports of attachment toward peers were reported after two weeks of OT treatment. Further, treatment-induced changes were most pronounced for participants with less secure attachment towards their peers. indicating that normal variance at baseline modulated treatment response. OT treatment was additionally associated with changes in mood, indicating decreases in feelings of tension and (tentatively) anger in the OT group, not in the placebo group. Further, at the end of the two-week trial, both treatment groups (OT, placebo) reported to experience an increase in social responsiveness and quality of life, but the effects were only specific to the OT-treatment in terms of reports on 'social motivation'. In summary, the observed improvements on state and trait dimensions of attachment after a multiple-dose treatment with OT provide further evidence in support of a pivotal role of OT in promoting the experience of attachment.

Direct eye contact enhances mirroring of others' movements: A transcranial magnetic stimulation study.

Direct eye contact is a powerful social cue to regulate interpersonal interactions. Previous behavioral studies showed a link between eye contact and motor mimicry, indicating that the automatic mimicry of observed hand movements is significantly enhanced when direct eye contact exists between the observer and the observed model. In the present study, we aim to investigate the neurophysiological basis of the previously reported behavioral enhancements. Here, transcranial magnetic stimulation (TMS) was applied to assess changes in cortico-motor excitability at the level of the primary motor cortex (M1) to explore whether and how the motor system is facilitated from observing others' hand movements and, in particular, how this process is modulated by eye contact. To do so, motor evoked potentials (MEPs) were collected from two hand muscles while participants received single-pulse TMS and naturally observed video clips of an actor showing hand opening movements or static hands. During the observation, either direct or averted eye gaze was established between the subject and the observed actor. Our findings show a clear effect of eye gaze on observation-induced motor facilitation. This indicates that the mapping or 'mirroring' of others' movements is significantly enhanced when movement observation is accompanied by direct eye gaze compared to averted eye gaze. Our results support the notion that eye contact is a powerful social signal with the ability to direct human non-verbal social behavior. Furthermore, our findings are important for understanding the role of the mirror motor system in the mapping of socially relevant actions.

Influence of oxytocin on emotion recognition from body language: A randomized placebo-controlled trial.

The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. One mechanism by which OT is hypothesized to promote prosocial behavior is by enhancing the processing of socially relevant information from the environment. With the present study, we explored to what extent OT can alter the 'reading' of emotional body language as presented by impoverished biological motion point light displays (PLDs). To do so, a double-blind between-subjects randomized placebo-controlled trial was conducted, assessing performance on a bodily emotion recognition task in healthy adult males before and after a single-dose of intranasal OT (24 IU). Overall, a single-dose of OT administration had a significant effect of medium size on emotion recognition from body language. OT-induced improvements in emotion recognition were not differentially modulated by the emotional valence of the presented stimuli (positive versus negative) and also, the overall tendency to label an observed emotional state as 'happy' (positive) or 'angry' (negative) was not modified by the administration of OT. Albeit moderate, the present findings of OT-induced improvements in bodily emotion recognition from whole-body PLD provide further support for a link between OT and the processing of socio-communicative cues originating from the body of others.