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Introduction: Gait disorders and gait-related cognitive tests were recently linked to future Alzheimer's Disease (AD) dementia diagnosis in amnestic Mild Cognitive Impairment (aMCI). This study aimed to evaluate the predictive power of gait disorders and gait-related neuropsychological performances for future AD diagnosis in aMCI through machine learning (ML)., Methods: A sample of 253 aMCI (stable, converter) individuals were included. We explored the predictive accuracy of four predictors (gait profile plus MMSE, DSST, and TMT-B) previously identified as critical for the conversion from aMCI to AD within a 36-month follow-up. Supervised ML algorithms (Support Vector Machine [SVM], Logistic Regression, and k-Nearest Neighbors) were trained on 70% of the dataset, and feature importance was evaluated for the best algorithm., Results: The SVM algorithm achieved the best performance. The optimized training set performance achieved an accuracy of 0.67 (sensitivity = 0.72; specificity = 0.60), improving to 0.70 on the test set (sensitivity = 0.79; specificity = 0.52). Feature importance revealed MMSE as the most important predictor in both training and testing, while gait type was important in the testing phase., Discussion: We created a predictive ML model that is capable of identifying aMCI at high risk of AD dementia within 36 months. Our ML model could be used to quickly identify individuals at higher risk of AD, facilitating secondary prevention (e.g., cognitive and/or physical training), and serving as screening for more expansive and invasive tests. Lastly, our results point toward theoretically and practically sound evidence of mind and body interaction in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tuena, Pupillo, Stramba-Badiale, Stramba-Badiale and Riva.)

Introduction: Mild Cognitive Impairment (MCI) often presents challenges related to spatial navigation and retention of spatial information. Navigating space involves intricate integration of bodily and environmental cues. Spatial memory is dependent on two distinct frame of reference systems for organizing this information: egocentric and allocentric frames of reference. Virtual Reality (VR) has emerged as a promising technology for enhancing spatial navigation skills and spatial memory by facilitating the manipulation of bodily, environmental, and cognitive cues., Methods: This usability study was based on a fully within-subjects design in which seven MCI patients underwent two kinds of VR conditions: participants were required to complete the ANTaging demo both in Oculus Rift S ( immersive condition ) and in Samsung UHD 4K monitor ( semi-immersive condition ). Participants were seated and they had to use a foot-motion pad to navigate and explore the environment to collect and relocate some objects in the virtual environment. Post-interaction, users provided feedback on their experiences. Additionally, usability, potential side effects, data analysis feasibility, and user preferences with immersive and semi-immersive technologies were assessed through questionnaires., Results: Results indicated higher usability ratings for the semi-immersive setup, with fewer negative effects reported compared to the immersive counterpart. According to qualitative analyses of the interviews, patients do seem to like both VR apparatuses even though the semi-immersive condition was perceived as the most suitable choice because of the size of the screen. Patients generally found it difficult to remember object locations. Participants expressed the need for more practice with the foot-motion pad, despite an overall positive experience. They generally would like to use this system to improve their memory., Discussion: Identifying these key aspects was crucial for refining the system before the upcoming clinical trial. This study sheds light on the potential of semi-immersive VR in aiding individuals with MCI, paving the way for enhanced spatial navigation interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stramba-Badiale, Tuena, Goulene, Cipresso, Morelli, Rossi, D’Avenio, Stramba-Badiale and Riva.)

Recent research has investigated the potential of psychedelic substances in treating various neurological and psychiatric disorders. In particular, there has been a growth in studies concerning the intersection of psychedelics, Virtual Reality (VR), and Cognitive Flexibility (CF). Indeed, the use of immersive technology allows the simulation of the perceptual and cognitive effects of psychedelic substances without the potential risks associated with them. CF is strongly associated with creative cognition, a complex cognitive mechanism involved in creative thinking and associated with the prefrontal cortex and the neural networks supporting executive functions, memory, attention, and spontaneous modes of thought. The Bayesian brain approach, which is rooted in predictive coding, has emerged as a promising framework for understanding the effects of psychedelic hallucinations on cognitive functioning. Psychedelic substances may enhance creativity by inducing a state of CF, allowing for a wider range of associations and possibilities to be explored and increasing openness to experience. A decline in cognitive abilities, including creative processing and divergent thinking, is observed during the aging process. In particular, studies on Mild Cognitive Impairment (MCI) show poorer performance in executive functions, including CF. The present paper suggests that psychedelic hallucinations induced by VR may help optimize the balance between top-down expectations and bottom-up sensory information. Therefore, enhanced CF and creativity may be crucial during the aging process for maintaining cognitive functions and preventing pathological conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Magni, Tuena and Riva.)

Machine Learning (ML) offers unique and powerful tools for mental health practitioners to improve evidence-based psychological interventions and diagnoses. Indeed, by detecting and analyzing different biosignals, it is possible to differentiate between typical and atypical functioning and to achieve a high level of personalization across all phases of mental health care. This narrative review is aimed at presenting a comprehensive overview of how ML algorithms can be used to infer the psychological states from biosignals. After that, key examples of how they can be used in mental health clinical activity and research are illustrated. A description of the biosignals typically used to infer cognitive and emotional correlates (e.g., EEG and ECG), will be provided, alongside their application in Diagnostic Precision Medicine, Affective Computing, and brain-computer Interfaces. The contents will then focus on challenges and research questions related to ML applied to mental health and biosignals analysis, pointing out the advantages and possible drawbacks connected to the widespread application of AI in the medical/mental health fields. The integration of mental health research and ML data science will facilitate the transition to personalized and effective medicine, and, to do so, it is important that researchers from psychological/ medical disciplines/health care professionals and data scientists all share a common background and vision of the current research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sajno, Bartolotta, Tuena, Cipresso, Pedroli and Riva.)

Oncological treatments are responsible for many of the physical changes (aesthetic and functional) associated with cancer. Because of this, cancer patients are at high risk of developing mental health problems. The aim of this study is to propose an innovative Virtual Reality (VR) training that uses a somatic technique (i.e., embodiment) to create a bridge with the bodily dimension of cancer. After undergoing a psycho-educational procedure, a combination of exposure, out-of-body experience, and body swapping will gradually train the patient to cope with cancer-related difficulties, increasing stress tolerance, and patient empowerment. The most engaging step of this advanced form of Stress Inoculation Training is the body swapping experience, which will guide the patient in embodying a resilient cancer patient who is facing similar difficulties. Through the VR ability to simulate the human brain functioning, and the potential of embodiment to hook to the somatic dimension of illness, we expect that once the concepts endured through the patient's experience of resilience are triggered, the patient will be more prone to implement functional coping strategies in real life, reaching empowerment and adjusting to the post-treatment difficulties. When the scenarios are built and the training tested, our intervention could be used to support patients with different oncological diseases and who are treated in different cancer hospitals, as well as patients with other non-oncological problems (e.g., social anxiety). Future research should focus on using our paradigm for other clinical populations, and supporting cancer patients in coping with different distressing situations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sansoni, Scarzello, Serino, Groff and Riva.)

Traditional neuropsychological evaluations are usually carried out using psychometric paper and pencil tests. Nevertheless, there is a continuous discussion concerning their efficacy to capture life-like abilities. The introduction of new technologies, such as Virtual Reality (VR) and 360° spherical photos and videos, has improved the ecological validity of the neuropsychological assessment. The possibility of simulating realistic environments and situations allows clinicians to evaluate patients in realistic activities. Moreover, 360° photos and videos seem to provide higher levels of graphical realism and technical user-friendliness compared to standard VR, regardless of their limitations in terms of interactivity. We developed a novel 360° tool, ObReco-2 (Object Recognition version 2), for the assessment of visual memory which simulates a daily situation in a virtual house. More precisely, patients are asked to memorize some objects that need to be moved for a relocation. After this phase, they are asked to recall them after 15 min and later to recognize them in the same environment. Here we present a first study about the usability of ObReco-2, and a second one exploring its clinical efficacy and updated usability data. We focused on Free Recall and Recognition scores, comparing the performances obtained by the participants in the standard and the 360° test. The preliminary results support the use of 360° technology for enhancing the ecological value of standard memory assessment tests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruni, Mancuso, Stramba-Badiale, Greci, Cavallo, Borghesi, Riva, Cipresso, Stramba-Badiale and Pedroli.)

Aging may be associated with conditions characterized by motor and cognitive alterations, which could have a detrimental impact on daily life. Although motors and cognitive aspects have always been treated as separate entities, recent literature highlights their relationship, stressing a strong association between locomotion and executive functions. Thus, designing interventions targeting the risks deriving from both components' impairments is crucial: the dual-task represents a starting point. Although its role in targeting and decreasing difficulties in aging is well known, most interventions are focused on a single domain, proposing a vertical model in which patients emerge only for a single aspect per time during assessment and rehabilitation. In this perspective, we propose a view of the individual as a whole between mind and body, suggesting a multicomponent and multidomain approach that could integrate different domains at the same time retracing lifelike situations. Virtual Reality, thanks to the possibility to develop daily environments with engaging challenges for patients, as well as to manage different devices to collect multiple data, provides the optimal scenario in which the integration could occur. Artificial Intelligence, otherwise, offers the best methodologies to integrate a great amount of various data to create a predictive model and identify appropriate and individualized interventions. Based on these assumptions the present perspective aims to propose the development of a new approach to an integrated, multimethod, multidimensional training in order to enhance cognition and physical aspects based on behavioral data, incorporating consolidated technologies in an innovative approach to neurology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruni, Borghesi, Mancuso, Riva, Stramba-Badiale, Pedroli and Cipresso.)

Cognitive frailty is defined as a clinical condition characterized by both physical frailty and cognitive impairment, without reaching the criteria for dementia. The major goal of rehabilitation intervention is to assist patients in performing ordinary personal duties without the assistance of another person, or at the very least to remove the need for additional support, using adaptive approaches and facilities. In this regard, home-based rehabilitation allows patients to continue an intervention begun in a hospital setting while also ensuring support and assistance when access to healthcare systems is limited, such as during the present pandemic situation. We thus present Brain m-App, a tablet-based application designed for home-based cognitive rehabilitation of frail subjects, addressing spatial memory, attention, and executive functions. This app exploits the potential of 360° videos which are well-suited to home-based rehabilitation. The Brain m-app is made up of 10 days of activities that include a variety of exercises. The activities were chosen based on those patients used to do during their clinical practice in the hospital with the aim to improve their independence and autonomy in daily tasks. The preliminary usability test, which was conducted on five older people, revealed a sufficient level of usability, however, the sample size was modest. Results from the clinical study with 10 patients, revealed that Brain m-App improved especially executive functions and memory performances., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pedroli, Mancuso, Stramba-Badiale, Cipresso, Tuena, Greci, Goulene, Stramba-Badiale, Riva and Gaggioli.)

The term "regenerative medicine" (RM) indicates an emerging trend in biomedical sciences that aims at replacing, engineering, or regenerating human cells, tissues, or organs to restore or establish normal function. So far, the focus of RM has been the physical body. Neuroscience, however, is now suggesting that mental disorders can be broadly characterized by a dysfunction in the way the brain computes and integrates the representations of the inner and outer body across time [bodily self-consciousness (BSC)]. In this perspective, we proposed a new kind of clinical intervention, i.e., "Regenerative Virtual Therapy" (RVT), which integrates knowledge from different disciplines, from neuroscience to computational psychiatry, to regenerate a distorted or faulty BSC. The main goal of RVT was to use technology-based somatic modification techniques to restructure the maladaptive bodily representations behind a pathological condition. Specifically, starting from a Bayesian model of our BSC (i.e., body matrix), we suggested the use of mindful attention, cognitive reappraisal, and brain stimulation techniques merged with high-rewarding and novel synthetic multisensory bodily experience (i.e., a virtual reality full-body illusion in sync with a low predictabIlity interoceptive modulation) to rewrite a faulty experience of the body and to regenerate the wellbeing of an individual. The use of RVT will also offer an unprecedented experimental overview of the dynamics of our bodily representations, allowing the reverse-engineering of their functioning for hacking them using advanced technologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Riva, Serino, Di Lernia and Pagnini.)

This research project has the goal to verify whether the application of neuromarketing techniques, such as implicit association test (IAT) techniques and emotional facial expressions analyses may contribute to the assessment of user experience (UX) during and after website navigation. These techniques have been widely and positively applied in assessing customer experience (CX); however, little is known about their simultaneous application in the field of UX. As a specific context, the experience raised by different websites from two well-known automotive brands was compared. About 160 Italian university students were enrolled in an online experimental study. Participants performed a Brand Association Reaction Time Test (BARTT) version of the IAT where the two brands were compared according to different semantic dimensions already used in the automotive field. After completing the BARTT test, the participants navigated the target website: 80 participants navigated the first brand website, while the other half navigated the second brand website (between-subject design). During the first 3 min of website navigation, emotional facial expressions were recorded. The participants were asked to freely navigate the website home page, look for a car model and its characteristics and price, use the customising tool, and in the end, look for assistance. After the website navigation, all the participants performed, a second time, the BARTT version of the IAT, where the two brands were compared again, this time to assess whether the website navigation may impact the Implicit Associations previously detected. A traditional evaluation of the two websites was carried on by means of the classic heuristic evaluation. Findings from this study show, first of all, the significant results provided by neuromarketing techniques in the field of UX, as IAT can provide a positive application for assessing UX played by brand websites, thanks to the comparison of eventual changes in time reaction between the test performed before and after website navigation exposure. Secondly, results from emotional facial expression analyses during the navigation of both brand websites showed significant differences between the two brands, allowing the researchers to predict the emotional impact raised by each website. Finally, the positive correlation with heuristic evaluation shows that neuromarketing can be successfully applied in UX., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mauri, Rancati, Gaggioli and Riva.)

Executive dysfunctions constitute a significant public health problem due to their high impact on everyday life and personal independence. Therefore, the identification of early strategies to assess and rehabilitate these impairments appears to be a priority. The ecological limitations of traditional neuropsychological tests and the numerous difficulties in administering tests in real-life scenarios have led to the increasing use of virtual reality (VR) and 360° environment-based tools for assessing executive functions (EFs) in real life. This perspective aims at proposing the development and implementation of Executive-functions Innovative Tool 360° (EXIT 360°), an innovative, enjoyable, and ecologically valid tool for a multidimensional and multicomponent evaluation of executive dysfunctions. EXIT 360° allows a complete and integrated executive functioning assessment through an original task for EFs delivered via a mobile-powered VR headset combined with eye tracker (ET) and electroencephalograms (EEG). Our tool is born as a 360°-based instrument, easily accessible and clinically usable, that will radically transform clinicians' and patient's assessment experience. In EXIT 360°, patients are engaged in a "game for health," where they must perform everyday subtasks in 360° daily life environments. In this way, the clinicians can obtain quickly more ecologically valid information about several aspects of EFs (e.g., planning, problem-solving). Moreover, the multimodal approach allows completing the assessment of EFs by integrating verbal responses, reaction times, and physiological data (eye movements and brain activation). Overall, EXIT 360° will allow obtaining simultaneously and in real time more information about executive dysfunction and its impact in real life, allowing clinicians to tailor the rehabilitation to the subject's needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Borgnis, Baglio, Pedroli, Rossetto, Riva and Cipresso.)

In catastrophic situations such as pandemics, patients' healthcare including admissions to hospitals and emergency services are challenged by the risk of infection and by limitations of healthcare resources. In such a setting, the use of telemedicine interventions has become extremely important. New technologies have proved helpful in pandemics as a solution to improve the quality of life in vulnerable patients such as persons with neurological diseases. Moreover, telemedicine interventions provide at-home solutions allowing clinicians to telemonitor and assess patients remotely, thus minimizing risk of infection. After a review of different studies using telemedicine in neurological patients, we propose a telemedicine process flow for healthcare of subjects with chronic neurological disease to respond to the new challenges for delivering quality healthcare during the transformation of public and private healthcare organizations around the world forced by COVID-19 pandemic contingency. This telemedicine process flow represents a replacement for in-person treatment and thereby the provision equitable access to the care of vulnerable people. It is conceptualized as comprehensive service including (1) teleassistance with patient counseling and medical treatment, (2) telemonitoring of patients' health conditions and any changes over time, as well as (3) telerehabilitation, i.e., interventions to assess and promote body functions, activities, and consecutively participation. The hereby proposed telemedicine process flow could be adopted on a large scale to improve the public health response during healthcare crises like the COVID-19 pandemic but could equally promote equitable health care independent of people's mobility or location with respect to the specialized health care center., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Matamala-Gomez, Bottiroli, Realdon, Riva, Galvagni, Platz, Sandrini, De Icco and Tassorelli.)

This observational study analyzes the impact of Internet use on the quality of life and well-being of the elderly. Specifically, it seeks to understand and clarify the effects of Internet use on relationships in terms of self-esteem, life satisfaction, and Online and Offline Social Support in a sample of senior and elderly Italian people (over 60 years of age). A cohort of 271 elderly people (133 males and 138 females) aged between 60 and 94 years old participated in the study: 236 were Internet Users while the other 35 were Non-Internet Users. The results showed that the time elderly people spend online has a negative effect on their perception of Offline Social Support (Offline Emotional and Informational and Offline Affective Social Support) and a positive effect on their perception of Online Social Support (particularly on Online Positive Social Interactions). Surprisingly, Internet use among elderly people seems to positively affect the perception of Offline Social Support. Indeed, elderly Internet Users have a more positive perception of Offline Social Support (particularly Offline Positive Social Interactions and Offline Affective Social Support) than Non-Internet Users. A discussion of this finding is provided, positing that the Internet seems to represent the technological side of a functional organ that allows the elderly to stay in closer touch with their family and friends and in doing so to also overcome some age-related difficulties., (Copyright © 2020 Benvenuti, Giovagnoli, Mazzoni, Cipresso, Pedroli and Riva.)

Mild cognitive impairment (MCI) refers to a subtle, general cognitive decline with a detrimental impact on elderlies' independent living and quality of life. Without a timely diagnosis, this condition can evolve into dementia over time, hence the crucial need for early detection, prevention, and rehabilitation. For this purpose, current neuropsychological interventions have been integrated with (i) virtual reality, which immerses the user in a controlled, ecological, and safe environment (so far, both virtual reality-based cognitive and motor rehabilitation have revealed promising positive outcomes); and (ii) non-invasive brain stimulation, i.e., transcranial magnetic or electric brain stimulation, which has emerged as a promising cognitive treatment for MCI and Alzheimer's dementia. To date, these two methods have been employed separately; only a few studies (limited to motor rehabilitation) have suggested their integration. The present paper suggests to extend this integration to cognitive rehabilitation as well as to provide a multimodal stimulation that could enhance cognitive training, resulting in a more efficient rehabilitation., (Copyright © 2020 Mancuso, Stramba-Badiale, Cavedoni, Pedroli, Cipresso and Riva.)

Background: Living in the time of the COVID-19 means experiencing not only a global health emergency but also extreme psychological stress with potential emotional side effects such as sadness, grief, irritability, and mood swings. Crucially, lockdown and confinement measures isolate people who become the first and the only ones in charge of their own mental health: people are left alone facing a novel and potentially lethal situation, and, at the same time, they need to develop adaptive strategies to face it, at home. In this view, easy-to-use, inexpensive, and scientifically validated self-help solutions aiming to reduce the psychological burden of coronavirus are extremely necessary., Aims: This pragmatic trial aims to provide the evidence that a weekly self-help virtual reality (VR) protocol can help overcome the psychological burden of the Coronavirus by relieving anxiety, improving well-being, and reinforcing social connectedness. The protocol will be based on the "Secret Garden" 360 VR video online (www.covidfeelgood.com) which simulates a natural environment aiming to promote relaxation and self-reflection. Three hundred sixty-degree or spherical videos allow the user to control the viewing direction. In this way, the user can explore the content from any angle like a panorama and experience presence and immersion. The "Secret Garden" video is combined with daily exercises that are designed to be experienced with another person (not necessarily physically together), to facilitate a process of critical examination and eventual revision of core assumptions and beliefs related to personal identity, relationships, and goals., Methods: This is a multicentric, pragmatic pilot randomized controlled trial involving individuals who experienced the COVID-19 pandemic and underwent a lockdown and quarantine procedures. The trial is approved by the Ethics Committee of the Istituto Auxologico Italiano. Each research group in all the countries joining the pragmatic trial, aims at enrolling at least 30 individuals in the experimental group experiencing the self-help protocol, and 30 in the control group, over a period of 3 months to verify the feasibility of the intervention., Conclusion: The goal of this protocol is for VR to become the "surgical mask" of mental health treatment. Although surgical masks do not provide the wearer with a reliable level of protection against the coronavirus compared with FFP2 or FFP3 masks, surgical masks are very effective in protecting others from the wearer's respiratory emissions. The goal of the VR protocol is the same: not necessarily to solve complex mental health problems but rather to improve well-being and preserve social connectedness through the beneficial social effects generated by positive emotions., (Copyright © 2020 Riva, Bernardelli, Browning, Castelnuovo, Cavedoni, Chirico, Cipresso, de Paula, Di Lernia, Fernández-Álvarez, Figueras-Puigderrajols, Fuji, Gaggioli, Gutiérrez-Maldonado, Hong, Mancuso, Mazzeo, Molinari, Moretti, Ortiz de Gortari, Pagnini, Pedroli, Repetto, Sforza, Stramba-Badiale, Tuena, Malighetti, Villani and Wiederhold.)

How our brain represents our body through the integration of internal and external sensory information so that we can interact with our surrounding environment has become a matter of interest especially in the field of neurorehabilitation. In this regard, there is an increasing interest in the use of multisensory integration techniques-such as the use of body ownership illusions-to modulate distorted body representations after brain damage. In particular, cross-modal illusions such as mirror visual feedback therapy (MVFT) have been widely used for motor rehabilitation. Despite the effectiveness of the MVFT for motor rehabilitation, there are some limitations to fully modify the distorted internal representation of the paretic limb in patients with stroke. A possible explanation for this relies on the physical limitations of the mirror in reproducing upper-limb distortions, which can result in a reduced sense of ownership of the mirrored limb. New digital technologies such as virtual reality (VR) and 360° videos allow researchers to create body ownership illusions by adapting virtual bodies so that they represent specific morphological characteristics including upper-limb distortions. In this manuscript, we present a new rehabilitation approach that employs full virtual body ownership illusions, using a 360° video system, for the assessment and modulation of the internal representation of the affected upper limb in stroke patients. We suggest modifying the internal representation of the upper limb to a normal position before starting motor rehabilitation training., (Copyright © 2020 Matamala-Gomez, Malighetti, Cipresso, Pedroli, Realdon, Mantovani and Riva.)

Elderly people affected by Mild Cognitive Impairment (MCI) usually report a perceived decline in cognitive functions that deeply impacts their quality of life. This subtle waning, although it cannot be diagnosable as dementia, is noted by caregivers on the basis of their relative's behaviors. Crucially, if this condition is also not detected in time by clinicians, it can easily turn into dementia. Thus, early detection of MCI is strongly needed. Classical neuropsychological measures - underlying a categorical model of diagnosis - could be integrated with a dimensional assessment approach involving Virtual Reality (VR) and Artificial Intelligence (AI). VR can be used to create highly ecologically controlled simulations resembling the daily life contexts in which patients' daily instrumental activities (IADL) usually take place. Clinicians can record patients' kinematics, particularly gait, while performing IADL (Digital Biomarkers). Then, Artificial Intelligence employs Machine Learning (ML) to analyze them in combination with clinical and neuropsychological data. This integrated computational approach would enable the creation of a predictive model to identify specific patterns of cognitive and motor impairment in MCI. Therefore, this new dimensional cognitive-behavioral assessment would reveal elderly people's neural alterations and impaired cognitive functions, typical of MCI and dementia, even in early stages for more time-sensitive interventions., (Copyright © 2020 Cavedoni, Chirico, Pedroli, Cipresso and Riva.)

The aim of this perspective is to propose and discuss the integration of transcranial magnetic stimulation (TMS) over the dorsolateral prefrontal cortex with virtual reality (VR) food exposure for therapeutic interventions for food addiction. "Food addiction" is a dysfunctional eating pattern which is typically observed in eating disorders (ED) such as bulimia nervosa and binge eating disorder. Food addiction has been compared to substance use disorder due to the necessity of consuming a substance (food) and the presence of a dependence behavior. In recent years, VR has been applied in the treatment of ED because it triggers psychological and physiological responses through food exposure in place of real stimuli. Virtual reality-Cue exposure therapy has been proven as a valid technique for regulating anxiety and food craving in ED. More, TMS has been proven to modulate circuits and networks implicated in neuropsychiatric disorders and is effective in treating addiction such as nicotine craving and consumption and cocaine use disorder. The combination of a simulative technology and a neurostimulation would presumably provide better improvement compared to a single intervention because it implies the presence of both cognitive and neuropsychological techniques. The possible advantage of this approach will be discussed in the perspective., (Copyright © 2020 Stramba-Badiale, Mancuso, Cavedoni, Pedroli, Cipresso and Riva.)

Background: The COVID-19 pandemic had a massive impact on health care systems, increasing the risks of psychological distress in health professionals. This study aims at assessing the prevalence of burnout and psychopathological conditions in health professionals working in a health institution in the Northern Italy, and to identify socio-demographic, work-related and psychological predictors of burnout. Methods: Health professionals working in the hospitals of the Istituto Auxologico Italiano were asked to participate to an online anonymous survey investigating socio-demographic data, COVID-19 emergency-related work and psychological factors, state anxiety, psychological distress, post-traumatic symptoms and burnout. Predictors of the three components of burnout were assessed using elastic net regression models. Results: Three hundred and thirty health professionals participated to the online survey. Two hundred and thirty-five health professionals (71.2%) had scores of state anxiety above the clinical cutoff, 88 (26.8%) had clinical levels of depression, 103 (31.3%) of anxiety, 113 (34.3%) of stress, 121 (36.7%) of post-traumatic stress. Regarding burnout, 107 (35.7%) had moderate and 105 (31.9%) severe levels of emotional exhaustion; 46 (14.0%) had moderate and 40 (12.1%) severe levels of depersonalization; 132 (40.1%) had moderate and 113 (34.3%) severe levels of reduced personal accomplishment. Predictors of all the three components of burnout were work hours, psychological comorbidities, fear of infection and perceived support by friends. Predictors of both emotional exhaustion and depersonalization were female gender, being a nurse, working in the hospital, being in contact with COVID-19 patients. Reduced personal accomplishment was also predicted by age. Conclusions: Health professionals had high levels of burnout and psychological symptoms during the COVID-19 emergency. Monitoring and timely treatment of these conditions is needed., (Copyright © 2020 Giusti, Pedroli, D'Aniello, Stramba Badiale, Pietrabissa, Manna, Stramba Badiale, Riva, Castelnuovo and Molinari.)

According to a growing body of studies, people's ability to forecast future emotional experiences is generally biased. Nonetheless, the existing literature has mainly explored affective forecasting in relation to specific events, whereas little is still known about the ability to make general estimations of future emotional states. Based on existing evidence suggesting future-oriented disposition as a key factor for mental health, the aims of the current study were (1) to investigate the relationship between negative (NA) and positive (PA) affective forecasting biases and perceived psychological well-being, and (2) to explore whether positively biased predictions are associated with resilience and foster one's skills to cope with stressful events. To do so, we asked 85 undergraduate students to forecast PA and NA over 2 weeks, as well as to report their daily affect through a web-based Ecological Momentary Assessment. According to the results, positively biased PA forecasting (i.e., overestimating positive emotional states) was associated with greater perceived psychological well-being and higher resilience. When high levels of stress were experienced, participants holding an optimistic, yet biased, estimation of future PA were more likely to successfully manage stressors, thus maintaining lower levels of NA and higher levels of positive emotions. We suggest that positively biased PA forecasting is an adaptive cognitive distortion that boosts people's resilience and mental health, thus opening new avenues for the promotion of psychological well-being., (Copyright © 2020 Colombo, Fernández-Álvarez, Suso-Ribera, Cipresso, García-Palacios, Riva and Botella.)

Episodic memory is essential to effectively perform a number of daily activities, as it enables individuals to consciously recall experiences within their spatial and temporal environments. Virtual Reality (VR) serves as an efficacious instrument to assess cognitive functions like attention and memory. Previous studies have adopted computer-simulated VR to assess memory, which realized greater benefits compared to traditional procedures (paper and pencil). One of the most recent trends of immersive VR experiences is the 360° technology. In order to evaluate its capabilities, this study aims to compare memory performance through two tasks: immersive task and non-immersive task. These tasks differ based on the participant's view of the 360° picture: (1) head-mounted display (HMD) for immersive task and (2) tablet for non-immersive task. This study seeks to compare how memory is facilitated in both the 360° immersive picture as well as the non-immersive 360° picture. A repeated measure design was carried out in a sample of 42 participants, randomized into two groups of 21. Group 1 first observed Picture A (immersive) followed by Picture B (non-immersive) while Group 2 began with Picture B and then looked at Picture A. Each 360° picture contains specific items with some items appearing in both. Memory evaluation is assessed immediately after the exposure (recall task), then again after a 10-min delay (recognition task). Results reveal that Group 1, which began with the immersive task, demonstrated stronger memory performance in the long term as compared to Group 2, which began with the non-immersive task. Preliminary data ultimately supports the efficacy of the 360° technology in evaluating cognitive function., (Copyright © 2019 Ventura, Brivio, Riva and Baños.)

Frailty is a pre-clinical condition that worsens physical health and quality of life. One of the most frequent symptoms of frailty is an increased risk of falling. In order to reduce this risk, we propose an innovative virtual reality motor rehabilitation program based on an immersive tool. All exercises will take place in the CAVE, a four-screen room with a stationary bike. The protocol will include two types of exercises for the improvement of balance: "Positive Bike" and "Avoid the Rocks." We will choose evaluation scales related to the functional aspects and subjective perception of balance. Our aim is to prove that our innovative motor rehabilitation protocol is as effective as or more effective than classical rehabilitation., (Copyright © 2019 Pedroli, Cipresso, Greci, Arlati, Boilini, Stefanelli, Rossi, Goulene, Sacco, Stramba-Badiale, Gaggioli and Riva.)

In the last decades, emotion regulation (ER) received increasing attention and became one of the most studied topics within the psychological field. Nevertheless, this construct has not been fully updated with the latest technological advancements. In this perspective, we will show how diverse technologies, such as virtual reality (VR), wearable biosensors, smartphones, or biofeedback techniques, can be applied to the understanding, assessment, and intervention of ER. After providing a brief overview of the currently available technological developments, we will discuss the benefits of incorporating new technologies in ER field, including ecological validity, intervention personalization, and the integration of understudied facets of ER, such as the implicit and interpersonal dimension.

The absence of self-awareness is a crucial aspect in the symptomatology of various neurodegenerative disorders. This characteristic becomes relevant due to the strong implications it has on the patient's quality of life, on the effects that functional dependence has on the caregiver and on the efficacy of the therapy. Faced with a construct as complex as self-awareness, there are in the literature investigations on different aspects of this phenomenon, such as the creation of cognitive models, the study of the neural substrate and the research of appropriate assessment methods that can reliably detect this function. With regard to the assessment methods, there are methodologies in the literature that provide complementary information. The first modality is a quantitatively online measurement based on the discrepancy between the estimate of the patient of his performance and his actual performance, but often neglecting the ecological validity and the real functioning of the subject. The second kind collecting subjective information on the actual daily functioning of the patient resulting from clinical observation or interviews with the subject and caregivers, but obtaining offline information on the functioning of the subject, liable to bias that may imply an overestimation or underestimation of subject's ability. The absence of acknowledged metacognitive functional assessment with normative data to evaluate awareness winks at the emerging and increasingly consistent use of virtual reality (VR) also in the context of cognitive research and clinical assessment. This article aims to make a theoretical proposal regarding the use of this innovative and promising tool as a supplement to the assessment methods of self-awareness.

Spatial cognition is an umbrella term used to refer to the complex set of abilities necessary to encode, categorize, and use spatial information from the surrounding environment to move effectively and orient within it. Experimental studies indicate that the cerebellum belongs to the neural network involved in spatial cognition, although its exact role in this function remains unclear. Our aim was to investigate in a pilot study using a virtual reality navigation task in healthy subjects whether cerebellar transcranial direct current stimulation (tDCS), a non-invasive technique, influences spatial navigation. Forty healthy volunteers (24 women; age range = 20-42 years; years of education range 13-18) were recruited. The virtual reality spatial navigation task comprised two phases: encoding, in which participants actively navigated the environment and learned the spatial locations for one object, and retrieval, in which they retrieved the position of the object they had discovered and memorized in the previous encoding phase, starting from another starting point. Participants received tDCS stimulation (anodal or sham according to the experimental condition they were assigned to) for 20 min before beginning the retrieval phase. Our results showed that cerebellar tDCS left the accuracy of the three indexes used to measure effective navigational abilities unchanged. Hence, cerebellar tDCS had no influence on the retrieval phase for the spatial maps stored. Further studies, enrolling a larger sample and testing a different stimulation protocol, may give a greater insight into the role of the cerebellum in spatial navigation.

Although it is noted that interpersonal sensorimotor coordination can influence several high-level socio-cognitive processes, its impact on creative collaboration is nearly unexplored. Here, we investigated the effects of a form of sensorimotor coordination, that is, sensorimotor synchronization, on a subsequent creative collaboration task. 60 pairs ( n total = 120 participants) formed by previously unacquainted individuals performed a tower-building task either jointly or alone, followed by a dyadic creativity task. Tower building time in the joint condition was recorded through a sensorized platform and creativity performance was evaluated by two independent raters based on the quantity and quality of generated ideas. We controlled for gender composition and for the disposition to cooperate and to adopt a creative, analytical style. Results showed that male-male couples were more creative after the joint-action condition, whereas female-female and mixed-gender couples were more creative after the solo condition. Regression analyses of tower building time on creativity performance revealed that building time was a significant predictor of creativity dimensions in male-male and in mixed-gender couples but did not predict creative performance in female-female couples. Overall, these findings suggest that the manipulation of sensorimotor coordination can influence performance in a subsequent creative collaboration task, with the nature, and magnitude of this effect depending on the gender composition of the dyads. These results have potential implications for the design of sensorimotor-based strategies to enhance dyadic creative performance in several contexts, especially for the organizational settings.

Bruton's tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role of p65BTK in tumors of the central nervous system (CNS). We selected a large cohort of patients with glial tumors ( n = 71) and analyzed the expression of p65BTK in different histotypes and correlation with clinical parameters. Sections were stained with glial fibrillary acidic protein (GFAP), p53, epidermal growth factor receptor (EGFR), S100, vimentin, and epithelial membrane antigen (EMA) antibodies. Glioma stem cell (GSC) lines, isolated from glioblastoma multiforme (GBM), were treated with different concentrations of ibrutinib, a specific inhibitor of BTK, in order to evaluate their metabolic activity, mitotic index and mortality. Moreover, an orthotopic xenotransplant of GSC from human GBM was used to evaluate the expression of p65BTK in the brain of immunodeficient mice. p65BTK was expressed in GSC and in gemistocytes in human gliomas at different histological grade. We found a significant correlation between BTK expression and low-grade (LG) tumors ( p ≤ 0.05) and overall survival (OS) of patients with grade III gliomas ( p ≤ 0.05), suggestive of worst prognosis. Interestingly, the expression of p65BTK remained restricted exclusively to gemistocytic cells in the xenograft mouse model. Ibrutinib administration significantly reduced metabolic activity and mitotic index and increased mortality in GSC, highlighting the specific role of p65BTK in cell proliferation and survival. In conclusion, our data demonstrated that p65BTK is expressed in glioma tumors, restricted to gemistocytic cells, has a key role in GSC and has a bad prognostic value, thus highlighting the importance of future research for targeted therapy of human gliomas.

Anorexia nervosa (AN) is a disorder characterized by alterations in body perception. Recent literature suggested that AN can also impair the processing of stimuli from inside the body (i.e., interoceptive) however, very few studies performed a complete interoceptive assessment exploring the evolution of the interoceptive dimensions before and after the subject's recovery. To address this gap in knowledge, this study presented the case of Diana, a 25 years old woman affected by AN. At hospital admission, Diana performed a complete interoceptive assessment for accuracy (IAc), metacognitive awareness (IAw), sensibility (IAs), and interoceptive buffer saturation (IBs) - a new index that behaviourally evaluated the amount of interoceptive processing. Measures were repeated at the end of an outpatients rehabilitative hospital program, after Diana's recovery. Results were confronted with a control ( N = 4) of healthy female subjects. Analyses indicated severe deficits in accuracy, buffer saturation, and sensibility compared to control group. Conversely, metacognitive awareness was pathologically enhanced. After the rehabilitative hospital program, Diana's clinical condition was largely improved and this reflected back on the interoceptive patterns that appeared restored, with no difference in interoceptive accuracy and metacognition compared to the control group. In conclusion, results indicated a very specific dissociation between interoceptive axes in AN with pervasive deficits in perception and processing that were accompanied by a pathologically enhanced confidence in the wrong perceptions. This case study reported an interesting and unique clinical pattern with a severe dissociation between interoceptive perceptions that nonetheless appeared restored after the subject's recovery, highlighting the role of interoceptive assessment in the clinical evolution of AN.