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Background: The rise in life expectancy is associated with an increase in long-term and gradual cognitive decline. Treatment effectiveness is enhanced at the early stage of the disease. Therefore, there is a need to find low-cost and ecological solutions for mass screening of community-dwelling older adults., Objective: This work aims to exploit automatic analysis of free speech to identify signs of cognitive function decline., Methods: A sample of 266 participants older than 65 years were recruited in Italy and Spain and were divided into 3 groups according to their Mini-Mental Status Examination (MMSE) scores. People were asked to tell a story and describe a picture, and voice recordings were used to extract high-level features on different time scales automatically. Based on these features, machine learning algorithms were trained to solve binary and multiclass classification problems by using both mono- and cross-lingual approaches. The algorithms were enriched using Shapley Additive Explanations for model explainability., Results: In the Italian data set, healthy participants (MMSE score≥27) were automatically discriminated from participants with mildly impaired cognitive function (20≤MMSE score≤26) and from those with moderate to severe impairment of cognitive function (11≤MMSE score≤19) with accuracy of 80% and 86%, respectively. Slightly lower performance was achieved in the Spanish and multilanguage data sets., Conclusions: This work proposes a transparent and unobtrusive assessment method, which might be included in a mobile app for large-scale monitoring of cognitive functionality in older adults. Voice is confirmed to be an important biomarker of cognitive decline due to its noninvasive and easily accessible nature., (©Emilia Ambrosini, Chiara Giangregorio, Eugenio Lomurno, Sara Moccia, Marios Milis, Christos Loizou, Domenico Azzolino, Matteo Cesari, Manuel Cid Gala, Carmen Galán de Isla, Jonathan Gomez-Raja, Nunzio Alberto Borghese, Matteo Matteucci, Simona Ferrante. Originally published in JMIR Aging (https://aging.jmir.org), 29.04.2024.)

Background: Genomics is an integral part of medical science; however, European citizens' literacy on basic genetic concepts is still poor. The aim of this study was to evaluate the effectiveness of Serious Games (SGs) in increasing genetic literacy in laypeople and to assess the impact of SGs on participants' perceived self-efficacy (SE) in managing genetic risk implications. Materials and Methods: Two minigames and an adventure game were created, together with leaflets reporting the same information as the SGs. Sixty participants enrolled at baseline and completed a brief sociodemographic questionnaire and an ad hoc questionnaire assessing their genetic knowledge. They were assigned to the SGs group (30 subjects) or to the Leaflets group (30 subjects) by matching age and sex. Both groups had about 40 minutes to play the SGs or to read the leaflets. In the postlearning session, participants completed the same genetic knowledge questionnaires administered at baseline and five items from the Self-Efficacy Scale, whereas the SGs group also filled in the In-Game Experience Questionnaire. Results and Conclusion: Results showed that learning genetic concepts through SGs was comparable to learning through leaflets. Playing SGs was also associated with poor feelings of frustration or annoyance, good engagement in the game challenges and contents, and positive feelings, particularly in subjects under 30 years. Participants perceiving SE increased significantly in both Leaflets and SGs groups, but the effect was higher for SGs players. SGs have the potential to increase genetic literacy in the public by making the learning process more engaging, pleasant and by enhancing SE.

The integration of Ambient Assisted Living (AAL) frameworks with Socially Assistive Robots (SARs) has proven useful for monitoring and assisting older adults in their own home. However, the difficulties associated with long-term deployments in real-world complex environments are still highly under-explored. In this work, we first present the MoveCare system, an unobtrusive platform that, through the integration of a SAR into an AAL framework, aimed to monitor, assist and provide social, cognitive, and physical stimulation in the own houses of elders living alone and at risk of falling into frailty. We then focus on the evaluation and analysis of a long-term pilot campaign of more than 300 weeks of usages. We evaluated the system's acceptability and feasibility through various questionnaires and empirically assessed the impact of the presence of an assistive robot by deploying the system with and without it. Our results provide strong empirical evidence that Socially Assistive Robots integrated with monitoring and stimulation platforms can be successfully used for long-term support to older adults. We describe how the robot's presence significantly incentivised the use of the system, but slightly lowered the system's overall acceptability. Finally, we emphasise that real-world long-term deployment of SARs introduces a significant technical, organisational, and logistical overhead that should not be neglected nor underestimated in the pursuit of long-term robust systems. We hope that the findings and lessons learned from our work can bring value towards future long-term real-world and widespread use of SARs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)

Background: Early detection of gait impairments in older adults allows the early uncovering of fall risk and/or cognitive deficits, resulting in timely interventions. Dual-task paradigms have been shown to be more sensitive than single-task conditions for the detection of subtle yet relevant gait impairments., Research Question: Can a system - encompassing a pair of instrumented insoles and a customized mobile app - transparently and accurately study ecological walking activities in single- and dual-task conditions, with the aim of detecting early and subtle age-related alterations of gait?, Methods: The system was tested on 19 older adults during outdoor walking (two identical single-task trials and two motor-cognitive dual-task trials with the user engaged in a simple phone call and in a cognitive-demanding phone call). A single-task cognitive trial was included. Relative reliability of the gait parameters provided by the insoles during single-task walking was investigated (Intraclass Correlation Coefficient). The effect of dual tasking on both motor (Friedman test) and cognitive (Wilcoxon signed-rank test) domains was studied. To study usability, the system was tested on 5 older adults in real-life environment over 3 months., Results: Most of the parameters showed excellent reliability. Independently from the cognitive demand, walking while talking resulted in increased gait cycle and step time, with a prolonged stance phase due to an augmented double-support. Variability of gait cycle and stance phase increased only during the most demanding dual-task. Dual tasking resulted in a reduced cognitive score. Usability feedback were excellent, with users reporting to understand the usefulness of the devised system and to feel at ease when using the system and the insoles., Significance: This work paves the way toward fruitful applications of the devised system to achieve accurate and ecological monitoring of daily-life walking activities, with the final aim of detecting early and subtle alterations of gait., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Difficulties in handwriting, such as dysgraphia, impact several aspects of a child's everyday life. Current methodologies for the detection of such difficulties in children have the following three main weaknesses: (1) they are prone to subjective evaluation; (2) they can be administered only when handwriting is mastered, thus delaying the diagnosis and the possible adoption of countermeasures; and (3) they are not always easily accessible to the entire community., Objective: This work aims at developing a solution able to: (1) quantitatively measure handwriting features whose alteration is typically seen in children with dysgraphia; (2) enable their study in a preliteracy population; and (3) leverage a standard consumer technology to increase the accessibility of both early screening and longitudinal monitoring of handwriting difficulties., Methods: We designed and developed a novel tablet-based app Play Draw Write to assess potential markers of dysgraphia through the quantification of the following three key handwriting laws: isochrony, homothety, and speed-accuracy tradeoff. To extend such an approach to a preliteracy age, the app includes the study of the laws in terms of both word writing and symbol drawing. The app was tested among healthy children with mastered handwriting (third graders) and those at a preliterate age (kindergartners)., Results: App testing in 15 primary school children confirmed that the three laws hold on the tablet surface when both writing words and drawing symbols. We found significant speed modulation according to size (P<.001), no relevant changes to fraction time for 67 out of 70 comparisons, and significant regression between movement time and index of difficulty for 44 out of 45 comparisons (P<.05, R 2 >0.28, 12 degrees of freedom). Importantly, the three laws were verified on symbols among 19 kindergartners. Results from the speed-accuracy exercise showed a significant evolution with age of the global movement time (circle: P=.003, square: P<.001, word: P=.001), the goodness of fit of the regression between movement time and accuracy constraints (square: P<.001, circle: P=.02), and the index of performance (square: P<.001). Our findings show that homothety, isochrony, and speed-accuracy tradeoff principles are present in children even before handwriting acquisition; however, some handwriting-related skills are partially refined with age., Conclusions: The designed app represents a promising solution for the screening of handwriting difficulties, since it allows (1) anticipation of the detection of alteration of handwriting principles at a preliteracy age and (2) provision of broader access to the monitoring of handwriting principles. Such a solution potentially enables the selective strengthening of lacking abilities before they exacerbate and affect the child's whole life., (©Linda Greta Dui, Francesca Lunardini, Cristiano Termine, Matteo Matteucci, Natale Adolfo Stucchi, Nunzio Alberto Borghese, Simona Ferrante. Originally published in JMIR Serious Games (http://games.jmir.org), 22.10.2020.)

Background: Dementia is a major and growing health problem, and early diagnosis is key to its management., Objective: With the ultimate goal of providing a monitoring tool that could be used to support the screening for cognitive decline, this study aims to develop a supervised, digitized version of 2 neuropsychological tests: Trail Making Test and Bells Test. The system consists of a web app that implements a tablet-based version of the tests and consists of an innovative vocal assistant that acts as the virtual supervisor for the execution of the test. A replay functionality is added to allow inspection of the user's performance after test completion., Methods: To deploy the system in a nonsupervised environment, extensive functional testing of the platform was conducted, together with a validation of the tablet-based tests. Such validation had the two-fold aim of evaluating system usability and acceptance and investigating the concurrent validity of computerized assessment compared with the corresponding paper-and-pencil counterparts., Results: The results obtained from 83 older adults showed high system acceptance, despite the patients' low familiarity with technology. The system software was successfully validated. A concurrent validation of the system reported good ability of the digitized tests to retain the same predictive power of the corresponding paper-based tests., Conclusions: Altogether, the positive results pave the way for the deployment of the system to a nonsupervised environment, thus representing a potential efficacious and ecological solution to support clinicians in the identification of early signs of cognitive decline., (©Francesca Lunardini, Matteo Luperto, Marta Romeo, Nicola Basilico, Katia Daniele, Domenico Azzolino, Sarah Damanti, Carlo Abbate, Daniela Mari, Matteo Cesari, Nunzio Alberto Borghese, Simona Ferrante. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 21.09.2020.)

Telemonitoring is one of the most expedient answers to the strong need for preventive care imposed by the rapidly aging society. We propose an innovative solution to the detection of early signs of frailty by presenting a serious game controlled by a smart sensorized soft plastic ball, designed to achieve continuous home-based monitoring of muscle weakness in older adults. Design, development, and testing of the smart ball and of the game interface devised to guide the monitoring procedure are presented. Reliability and concurrent validity of the system in measuring maximal grip strength against the clinical standard Jamar ® were evaluated. Serious game usability and acceptance were investigated on 26 elderlies. Smart ball and Jamar measurements were well correlated (0.76 and 0.80 for dominant and non-dominant hands) and test-retest reliability of pressure measurements was excellent (intraclass correlation coefficient >0.94). The serious game was well accepted by the 96.1 percent of participants, who provided a strongly positive usability score (87.7/100). The smart ball-driven serious game demonstrated excellent reliability and good validity in measuring grip strength. The proposed smart ball-driven serious game can be used for home self-monitoring of grip strength in elderlies.

The analysis of the writing gesture has been successfully investigated in the diagnosis of age-related diseases, but the current technologies and methods still do not allow the ecological daily monitoring of handwriting, mostly because they rely on standardized writing protocols. In this study, we first designed and validated a novel electronic ink pen, equipped with motion and writing force sensing, for the ecological daily-life monitoring of handwriting in uncontrolled environments. We used the pen to acquire writing activities from healthy adults, from which we computed useful handwriting and tremor indicators. We evaluated the reliability of our measurements by computing the intraclass correlation coefficients (ICC) and the minimal detectable changes (MDC). Moderate to excellent reliability were obtained for all the handwriting indicators computed in two different writing tasks. MDC values can be used as reference to discriminate a real change in the handwriting parameters from a measurement error in longitudinal studies. These results pave the way towards the use of the pen for daily life handwriting monitoring.

People who survive a stroke usually suffer movement disorders resulting in involuntary abnormal movements. Intensive and repetitive physiotherapy is often a key to functional restoration of movements. Rehabilitation centers have recently offered balance training supported by exergames in addition to conventional therapy. The primary objective was to investigate different types of balance training (multi-exergaming and conventional) in addition to a conventional 6-week physiotherapy program. Furthermore, we examined the choice of an appropriate exergame to target balance training. We designed a randomized pilot trial. Hospital inpatients with stroke aged 33-65 were recruited and randomized into 2 groups by drawing lots; a control group receiving 1 week of conventional balance training and an exergaming group 1 week of multiple-game exergaming, comprising single leg exercises, weight shifting, balancing and standing up. Center of pressure was monitored for the exergaming group and clinical data were collected (non-blinded assessment) using Four Square Step Test, Timed Up and Go, 10 m Walk Test, Romberg, Sharpened Romberg, Clinical Test for Sensory Interaction in Balance in both groups. Statistical tests were used to find significant ( p < 0.05) differences and Cohen's U3 for effect sizes. Recruited participants (20/30) met the inclusion criteria and were randomized; 10 per group. 1 participant of the exergaming group was excluded from center of pressure analysis. Both groups demonstrated substantively and statistically significant improvements of functional balance, in particular the exergaming group (FSST p = 0.009, U3 = 0.9 and 10 MWT p = 0.008, U3 = 0.9). However, significant differences between the groups were found in tests with eyes closed, Sharpened Romberg test ( p = 0.05) and standing on the right leg ( p = 0.035). The center of pressure area decreased up to 20% for the exergaming group. Both types of additional balance training demonstrated comparable outcomes, however, the multi-exergaming could target specific motor control disorders by the selection of exergames according to Gentile's taxonomy. We may not prioritize exergaming due to the low statistical power of clinical outcomes. However, exergaming enables independent balance training, which is feasible without strenuous physiotherapy and may thus be crucial for future home or telerehabilitation services. Clinical Trial Registration: www.clinicaltrials.gov/, identifier NCT03282968., (Copyright © 2020 Cikajlo, Rudolf, Mainetti and Borghese.)

We describe here a platform for autonomous hand rehabilitation and telemonitoring of young patients. A toy embedding the electronics required to sense fingers pressure in different grasping modalities is the core element of this platform. The system has been realized following the user-centered design methodology taking into account stakeholder needs from start: clinicians require reliable measurements and the ability to get a picture remotely on rehabilitation progression; children have asked to interact with a pleasant and comfortable object that is easy to use, safe, and rewarding. These requirements are not antithetic, and considering both since the design phase has allowed the realization of a platform reliable to clinicians and keen to be used by young children., Competing Interests: The authors declare no conflict of interest.

In this paper we describe and validate a new coordinate-based method for meta-analysis of neuroimaging data based on an optimized hierarchical clustering algorithm: CluB (Clustering the Brain). The CluB toolbox permits both to extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and to explore each single cluster of activation for its composition according to the cognitive dimensions of interest. This last step, called "cluster composition analysis," permits to explore neurocognitive effects by adopting a factorial-design logic and by testing the working hypotheses using either asymptotic tests, or exact tests either in a classic inference, or in a Bayesian-like context. To perform our validation study, we selected the fMRI data from 24 normal controls involved in a reading task. We run a standard random-effects second level group analysis to obtain a "Gold Standard" of reference. In a second step, the subject-specific reading effects (i.e., the linear t-contrast "reading > baseline") were extracted to obtain a coordinates-based database that was used to run a meta-analysis using both CluB and the popular Activation Likelihood Estimation method implemented in the software GingerALE. The results of the two meta-analyses were compared against the "Gold Standard" to compute performance measures, i.e., sensitivity, specificity, and accuracy. The GingerALE method obtained a high level of accuracy (0.967) associated with a high sensitivity (0.728) and specificity (0.971). The CluB method obtained a similar level of accuracy (0.956) and specificity (0.969), notwithstanding a lower level of sensitivity (0.14) due to the lack of prior Gaussian transformation of the data. Finally, the two methods obtained a good-level of concordance (AC 1 = 0.93). These results suggested that methods based on hierarchical clustering (and post-hoc statistics) and methods requiring prior Gaussian transformation of the data can be used as complementary tools, with the GingerALE method being optimal for neurofunctional mapping of pooled data according to simpler designs, and the CluB method being preferable to test more specific, and localized, neurocognitive hypotheses according to factorial designs., (Copyright © 2019 Berlingeri, Devoto, Gasparini, Saibene, Corchs, Clemente, Danelli, Gallucci, Borgoni, Borghese and Paulesu.)

Background: In the last decade, the family system has changed significantly. Although in the past, older people used to live with their children, nowadays, they cannot always depend on assistance of their relatives. Many older people wish to remain as independent as possible while remaining in their homes, even when living alone. To do so, there are many tasks that they must perform to maintain their independence in everyday life, and above all, their well-being. Information and communications technology (ICT), particularly robotics and domotics, could play a pivotal role in aging, especially in contemporary society, where relatives are not always able to accurately and constantly assist the older person., Objective: The aim of this study was to understand the needs, preferences, and views on ICT of some prefrail older people who live alone. In particular, we wanted to explore their attitude toward a hypothetical caregiver robot and the functions they would ask for., Methods: We designed a qualitative study based on an interpretative phenomenological approach. A total of 50 potential participants were purposively recruited in a big town in Northern Italy and were administered the Fried scale (to assess the participants' frailty) and the Mini-Mental State Examination (to evaluate the older person's capacity to comprehend the interview questions). In total, 25 prefrail older people who lived alone participated in an individual semistructured interview, lasting approximately 45 min each. Overall, 3 researchers independently analyzed the interviews transcripts, identifying meaning units, which were later grouped in clustering of themes, and finally in emergent themes. Constant triangulation among researchers and their reflective attitude assured trustiness., Results: From this study, it emerged that a number of interviewees who were currently using ICT (ie, smartphones) did not own a computer in the past, or did not receive higher education, or were not all young older people (aged 65-74 years). Furthermore, we found that among the older people who described their relationship with ICT as negative, many used it in everyday life. Referring to robotics, the interviewees appeared quite open-minded. In particular, robots were considered suitable for housekeeping, for monitoring older people's health and accidental falls, and for entertainment., Conclusions: Older people's use and attitudes toward ICT does not always seem to be related to previous experiences with technological devices, higher education, or lower age. Furthermore, many participants in this study were able to use ICT, even if they did not always acknowledge it. Moreover, many interviewees appeared to be open-minded toward technological devices, even toward robots. Therefore, proposing new advanced technology to a group of prefrail people, who are self-sufficient and can live alone at home, seems to be feasible., (©Katia Daniele, Maura Marcucci, Cesarina Cattaneo, Nunzio Alberto Borghese, Lucia Zannini. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.08.2019.)

This study aimed at evaluating whether people with a normal cognitive function can be discriminated from subjects with a mild impairment of cognitive function based on a set of acoustic features derived from spontaneous speech. Voice recordings from 90 Italian subjects (age >65 years; group 1: 47 subjects with MMSE>26; group 2: 43 subjects with 20≤ MMSE ≤26) were collected. Voice samples were processed using a MATLAB-based custom software to derive a broad set of known acoustic features. Linear mixed model analyses were performed to select the features able to significantly distinguish between groups. The selected features (% of unvoiced segments, duration of unvoiced segments, % of voice breaks, speech rate, and duration of syllables), alone or in addition to age and years of education, were used to build a learning-based classifier. The leave-one-out cross validation was used for testing and the classifier accuracy was computed. When the voice features were used alone, an overall classification accuracy of 0.73 was achieved. When age and years of education were additionally used, the overall accuracy increased up to 0.80. These performances were lower than the accuracy of 0.86 found in a recent study. However, in that study the classification was based on several tasks, including more cognitive demanding tasks. Our results are encouraging because acoustic features, derived for the first time only from an ecologic continuous speech task, were able to discriminate people with a normal cognitive function from people with a mild cognitive decline. This study poses the basis for the development of a mobile application performing automatic voice analysis on-the-fly during phone calls, which might potentially support the detection of early signs of functional cognitive decline.

The lowering costs of DNA sequencing and the diffusion of numerous Direct to Consumer Genetic Testing (DTC-GT) services have made genetic testing easily available to the general public who can buy them without any medical prescription or consultation. Nevertheless, the knowledge required to understand the provided results and their implications is still scarce in the general public. Starting from these considerations, we developed two mini-games and one serious game to increase people genetic literacy through experiential learning. The three games were tested for usability on a sample of 30 participants, 10 for each game, who were asked to report any positive or negative issue related to the games and to fulfill the Game Experience Questionnaire in order to evaluate their playing experience. Results from the three games show that players experienced moderate levels of immersion and flow, low levels of negative sensations, and a prevalence of positive emotions. In general, these encouraging results suggest that the proposed games are suitable to transmit genetic notions to the general public.

Background: Genetic testing and genetic risk information are gaining importance in personalized medicine and disease prevention. However, progress in these fields does not reflect increased knowledge and awareness of genetic risk in the general public., Objective: Our aim is to develop and test the efficacy of a suite of serious games, developed for mobile and Web platforms, in order to increase knowledge of basic genetic concepts and promote awareness of genetic risk management among lay people., Methods: We developed a new ad-hoc game and modified an arcade game using mechanics suitable to explain genetic concepts. In addition, we developed an adventure game where players are immersed in virtual scenarios and manage genetic risk information to make health-related and interpersonal decisions and modulate their lifestyle. The pilot usability testing will be conducted with a convenience sample of 30 adults who will be categorized into 3 groups and assigned to one game each. Participants will be asked to report any positive or negative issues arising during the game. Subsequently, they will be asked to complete the Game Experience Questionnaire. Finally, a total of 60 teenagers and adults will be enrolled to assess knowledge transfer. Thirty participants will be assigned to the experimental group and asked to play the serious games, and 30 participants will be assigned to the control group and asked to read leaflets on the genetic concepts conveyed by the games. Participants of both groups will fill out a questionnaire before and after the intervention to assess their topic-specific knowledge of genetics. Furthermore, both groups will complete the self-efficacy questionnaire, which assesses the level of confidence in using genetic information., Results: We obtained evidence of game usability in 2017. The data will be submitted to a peer-reviewed journal and used to improve the game design. Knowledge-transfer testing will begin in 2018, and we expect to collect preliminary data on the learning outcomes of serious games by December 2018., Conclusions: It is important to educate the general public about the impact of genetics and genetic testing on disease prevention and the consequent decision-making implications. Without such knowledge, individuals are more likely to make uninformed decisions or handover all decisions regarding genetic testing to their doctors. Technological innovations such as serious games might become a valid instrument to support public education and empowerment., International Registered Report Identifier (irrid): DERR1-10.2196/9288., (©Serena Oliveri, Renato Mainetti, Alessandra Gorini, Ilaria Cutica, Giulia Candiani, Nunzio Alberto Borghese, Gabriella Pravettoni. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.12.2018.)

Background: New technologies, such as telerehabilitation and gaming devices offer the possibility for patients to train at home. This opens the challenge of safety for the patient as he/she is called to exercise neither with a therapist on the patients' side nor with a therapist linked remotely to supervise the sessions., Aim: To study the safety, usability and patient acceptance of an autonomous telerehabilitation system for balance and gait (the REWIRE platform) in the patients home., Design: Cohort study., Setting: Community, in the stroke patients' home., Population: Fifteen participants with first-ever stroke, with a mild to moderate residual deficit of the lower extremities., Methods: Autonomous rehabilitation based on virtual rehabilitation was provided at the participants' home for twelve weeks. The primary outcome was compliance (the ratio between days of actual and scheduled training), analyzed with the two-tailed Wilcoxon Mann-Whitney test. Furthermore safety is defined by adverse events. The secondary endpoint was the acceptance of the system measured with the Technology Acceptance Model (TAM). Additionally, the cumulative duration of weekly training was analyzed., Results: During the study there were no adverse events related to the therapy. Patients performed on average 71% (range 39 to 92%) of the scheduled sessions. The TAM Questionnaire showed excellent values for stroke patients after the training. The average training duration per week was 99±53min., Conclusions: Autonomous telerehabilitation for balance and gait training with the REWIRE-system is safe, feasible and can help to intensive rehabilitative therapy at home., Clinical Rehabilitation Impact: Telerehabilitation enables safe training in home environment and supports of the standard rehabilitation therapy.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Visuospatial neglect due to stroke is characterized by the inability to perceive stimuli emerging in the area opposite to the side of brain damage. Besides adopting conventional rehabilitation methods to treat neglect symptoms, the use of virtual reality (VR) is becoming increasingly popular. We designed a series of 9 exergames aimed to improve exploration of the neglected side of space. When new VR interventions are designed, it is important to assess the usability aspects of such management strategies within the target population. To date, most studies used questionnaires to assess user satisfaction with the intervention or product being tested. However, only a combination of both quantitative and qualitative data allows a full picture of user perspective., Objective: The purpose of this study was to quantitatively and qualitatively assess patient and therapist perspectives of a VR intervention based on the series of 9 exergames designed to explore hemineglected space. Specifically, we wanted to evaluate (1) perceived-user friendliness of the exergames, (2) attitude towards using the exergames, and (3) intention to use the exergames in the future., Methods: A total of 19 participants (7 patients, 12 therapists) evaluated the exergames they had used 5 times a week during 3 weeks. The Technology Acceptance Model (TAM) questionnaire was filled out after the intervention. Based on those responses, we conducted focus group interviews (with therapists) and individual interviews (with patients). To analyze the TAM questionnaires, we used descriptive statistics. We adopted content and comparative analysis to analyze the interviews and drew illustration maps to analyze the focus group interviews., Results: The therapists took a more critical stance with a mean TAM questionnaire total score of 48.6 (SD 4.5) compared to the patients who had a mean total score of 56.1 (SD 12.3). The perceived user-friendliness score was 5.6 (SD 1.4) for patients and 4.9 (SD 1.4) for therapists. The attitude towards using the exergames was rated 4.8 (SD 1.9) by patients and 3.6 (SD 1.4) by therapists, respectively. The intention to use the exergames in the future was rated 3.9 (SD 2.1) by patients and 3.7 (SD 1.8) by therapists. We gained information on how to improve the exergames in the interviews., Conclusions: Patients and therapists perceived the exergames as user-friendly; however, using the games further with the actual test version was not perceived as conceivable. The therapists were generally more critical towards future use than the patients. Therefore, involving both users to achieve acceptable and user-friendly versions of game-based rehabilitation for the future is deemed crucial and warranted., Trial Registration: Clinicaltrials.gov NCT02353962; https://clinicaltrials.gov/ct2/show/NCT02353962 (Archived by WebCite at http://www.webcitation.org/6soxIJlAZ)., (©Bernadette C Tobler-Ammann, Elif Surer, Ruud H Knols, N Alberto Borghese, Eling D de Bruin. Originally published in JMIR Serious Games (http://games.jmir.org), 25.08.2017.)

Background: Use of exergames can complement conventional therapy and increase the amount and intensity of visuospatial neglect (VSN) training. A series of 9 exergames-games based on therapeutic principles-aimed at improving exploration of the neglected space for patients with VSN symptoms poststroke was developed and tested for its feasibility., Objectives: The goal was to determine the feasibility of the exergames with minimal supervision in terms of (1) implementation of the intervention, including adherence, attrition and safety, and (2) limited efficacy testing, aiming to document possible effects on VSN symptoms in a case series of patients early poststroke., Methods: A total of 7 patients attended the 3-week exergames training program on a daily basis. Adherence of the patients was documented in a training diary. For attrition, the number of participants lost during the intervention was registered. Any adverse events related to the exergames intervention were noted to document safety. Changes in cognitive and spatial exploration skills were measured with the Zürich Maxi Mental Status Inventory and the Neglect Test. Additionally, we developed an Eye Tracker Neglect Test (ETNT) using an infrared camera to detect and measure neglect symptoms pre- and postintervention., Results: The median was 14 out of 15 (93%) attended sessions, indicating that the adherence to the exergames training sessions was high. There were no adverse events and no drop-outs during the exergame intervention. The individual cognitive and spatial exploration skills slightly improved postintervention (P=.06 to P=.98) and continued improving at follow-up (P=.04 to P=.92) in 5 out of 7 (71%) patients. Calibration of the ETNT was rather error prone. The ETNT showed a trend for a slight median group improvement from 15 to 16 total located targets (+6%)., Conclusions: The high adherence rate and absence of adverse events showed that these exergames were feasible and safe for the participants. The results of the amount of exergames use is promising for future applications and warrants further investigations-for example, in the home setting of patients to augment training frequency and intensity. The preliminary results indicate the potential of these exergames to cause improvements in cognitive and spatial exploration skills over the course of training for stroke patients with VSN symptoms. Thus, these exergames are proposed as a motivating training tool to complement usual care. The ETNT showed to be a promising assessment for quantifying spatial exploration skills. However, further adaptations are needed, especially regarding calibration issues, before its use can be justified in a larger study sample., (©Bernadette C Tobler-Ammann, Elif Surer, Eling D de Bruin, Marco Rabuffetti, N Alberto Borghese, Renato Mainetti, Michele Pirovano, Lia Wittwer, Ruud H Knols. Originally published in JMIR Serious Games (http://games.jmir.org), 25.08.2017.)

Well-developed coordination of the upper extremities is critical for function in everyday life. Interlimb coordination is an intuitive, yet subjective concept that refers to spatio-temporal relationships between kinematic, kinetic and physiological variables of two or more limbs executing a motor task with a common goal. While both the clinical and neuroscience communities agree on the relevance of assessing and quantifying interlimb coordination, rehabilitation engineers struggle to translate the knowledge and needs of clinicians and neuroscientists into technological devices for the impaired. The use of ambiguous definitions in the scientific literature, and lack of common agreement on what should be measured, present large barriers to advancements in this area. Here, we present the different definitions and approaches to assess and quantify interlimb coordination in the clinic, in motor control studies, and by state-of-the-art robotic devices. We then propose a taxonomy of interlimb activities and give recommendations for future neuroscience-based robotic- and sensor-based assessments of upper limb function that are applicable to the everyday clinical practice. We believe this is the first step towards our long-term goal of unifying different fields and help the generation of more consistent and effective tools for neurorehabilitation.

Low-cost gaming technology offers promising devices for the rehabilitation of stroke patients at home. While several attempts have been made to use low-cost motion tracking devices (Kinect) or balance boards (Wii Board), the potential of low-cost haptic devices has yet to be explored in this context. The objective of this study was to investigate whether it is possible to influence postural stability with a low-cost device despite its technical limitations, and to explore the most promising modes of haptic interaction to increase and decrease postural stability. Two groups of younger subjects used a high-end (Omega.3) and a low-cost (Falcon) device respectively. A third group of older subjects used the Falcon. We show that light touch contact with the device improves stability, whereas the force tasks decrease it. The effects of the different tasks are consistent in the two age groups. Although there are differences in the participants' interaction with the two devices, the effect of the devices on postural stability is comparable. We conclude that a low-cost haptic device can be used to increase or decrease postural stability of healthy subjects with an age similar to that of typical stroke patients, in a safe and controllable way.

Background: Post-stroke recovery benefits from structured, intense, challenging, and repetitive therapy. Exergames have emerged as promising to achieve sustained therapy practice and patient motivation. This study assessed the usability and effects of exergames on balance and gait. Subjects and Methods: Sixteen elderly participants were provided with the study intervention based on five newly developed exergames. The participants were required to attend 36 training sessions; lasting for 20 minutes each. Adherence, attrition and acceptance were assessed together with (1) Berg Balance Scale, (2) 7-m Timed Up and Go, (3) Short Physical Performance Battery, (4) force platform stance tests, and (5) gait analysis. Results: Thirteen participants completed the study (18.8 percent attrition), without missing a single training session (100 percent adherence). Participants showed high acceptance of the intervention. Only minor adaptations in the program were needed based on the users' feedback. No changes in center of pressure area during quiet stance on both stable and unstable surfaces and no changes of walking parameters were detected. Scores for the Berg Balance Scale ( P =0.007; r =0.51), the 7-m Timed Up and Go ( P =0.002; r =0.56), and the Short Physical Performance Battery ( P =0.013; r =0.48) increased significantly with moderate to large effect sizes. Conclusion: Participants evaluated the usability of the virtual reality training intervention positively. Results indicate that the intervention improves gait- and balance-related physical performance measures in untrained elderly. The present results warrant a clinical explorative study investigating the usability and effectiveness of the exergame-based program in stroke patients.

The existence of multiple solutions in clustering, and in hierarchical clustering in particular, is often ignored in practical applications. However, this is a non-trivial problem, as different data orderings can result in different cluster sets that, in turns, may lead to different interpretations of the same data. The method presented here offers a solution to this issue. It is based on the definition of an equivalence relation over dendrograms that allows developing all and only the significantly different dendrograms for the same dataset, thus reducing the computational complexity to polynomial from the exponential obtained when all possible dendrograms are considered. Experimental results in the neuroimaging and bioinformatics domains show the effectiveness of the proposed method.

Although it is widely accepted that nouns and verbs are functionally independent linguistic entities, it is less clear whether their processing recruits different brain areas. This issue is particularly relevant for those theories of lexical semantics (and, more in general, of cognition) that suggest the embodiment of abstract concepts, i.e., based strongly on perceptual and motoric representations. This paper presents a formal meta-analysis of the neuroimaging evidence on noun and verb processing in order to address this dichotomy more effectively at the anatomical level. We used a hierarchical clustering algorithm that grouped fMRI/PET activation peaks solely on the basis of spatial proximity. Cluster specificity for grammatical class was then tested on the basis of the noun-verb distribution of the activation peaks included in each cluster. Thirty-two clusters were identified: three were associated with nouns across different tasks (in the right inferior temporal gyrus, the left angular gyrus, and the left inferior parietal gyrus); one with verbs across different tasks (in the posterior part of the right middle temporal gyrus); and three showed verb specificity in some tasks and noun specificity in others (in the left and right inferior frontal gyrus and the left insula). These results do not support the popular tenets that verb processing is predominantly based in the left frontal cortex and noun processing relies specifically on temporal regions; nor do they support the idea that verb lexical-semantic representations are heavily based on embodied motoric information. Our findings suggest instead that the cerebral circuits deputed to noun and verb processing lie in close spatial proximity in a wide network including frontal, parietal, and temporal regions. The data also indicate a predominant-but not exclusive-left lateralization of the network.

Objective: The aim of this article is to describe a game engine that has all the characteristics needed to support rehabilitation at home. The low-cost tracking devices recently introduced in the entertainment market allow measuring reliably at home, in real time, players' motion with a hands-free approach. Such systems have also become a source of inspiration for researchers working in rehabilitation. Computer games appear suited to guide rehabilitation because of their ability to engage the users. However, commercial videogames and game engines lack the peculiar functionalities required in rehabilitation: Games should be adapted to each patient's functional status, and monitoring the patient's motion is mandatory to avoid maladaptation. Feedback on performance and progression of the exercises should be provided. Lastly, several tracking devices should be considered, according to the patient's pathology and rehabilitation aims., Subjects and Methods: We have analyzed the needs of the clinicians and of the patients associated in performing rehabilitation at home, identifying the characteristics that the game engine should have., Results: The result of this analysis has led us to develop the Intelligent Game Engine for Rehabilitation (IGER) system, which combines the principles upon which commercial games are designed with the needs of rehabilitation. IGER is heavily based on computational intelligence: Adaptation of the difficulty level of the exercise is carried out through a Bayesian framework from the observation of the patient's success rate. Monitoring is implemented in fuzzy systems and based on rules defined for the exercises by clinicians. Several devices can be attached to IGER through an input abstraction layer, like the Nintendo ® (Kyoto, Japan) Wii™ Balance Board™, the Microsoft ® (Redmond, WA) Kinect, the Falcon from Novint Technologies (Albuquerque, NM), or the Tyromotion (Graz, Austria) Timo ® plate balance board. IGER is complemented with videogames embedded in a specific taxonomy developed to support rehabilitation progression through time., Conclusions: A few games aimed at postural rehabilitation have been designed and developed to test the functionalities of the IGER system. The preliminary results of tests on normal elderly people and patients with the supervision of clinicians have shown that the IGER system indeed does feature the characteristics required to support rehabilitation at home and that it is ready for clinical pilot testing at patients' homes.

We compared two Bayesian denoising algorithms for digital radiographs, based on Total Variation regularization and wavelet decomposition. The comparison was performed on simulated radiographs with different photon counts and frequency content and on real dental radiographs. Four different quality indices were considered to quantify the quality of the filtered radiographs. The experimental results suggested that Total Variation is more suited to preserve fine anatomical details, whereas wavelets produce images of higher quality at global scale; they also highlighted the need for more reliable image quality indices., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Video-games are becoming a common tool to guide patients through rehabilitation because of their power of motivating and engaging their users. Video-games may also be integrated into an infrastructure that allows patients, discharged from the hospital, to continue intensive rehabilitation at home under remote monitoring by the hospital itself, as suggested by the recently funded Rewire project., Objective: Goal of this work is to describe a novel low cost platform, based on video-games, targeted to neglect rehabilitation., Methods: The patient is guided to explore his neglected hemispace by a set of specifically designed games that ask him to reach targets, with an increasing level of difficulties. Visual and auditory cues helped the patient in the task and are progressively removed. A controlled randomization of scenarios, targets and distractors, a balanced reward system and music played in the background, all contribute to make rehabilitation more attractive, thus enabling intensive prolonged treatment., Results: Results from our first patient, who underwent rehabilitation for half an hour, for five days a week for one month, showed on one side a very positive attitude of the patient towards the platform for the whole period, on the other side a significant improvement was obtained. Importantly, this amelioration was confirmed at a follow up evaluation five months after the last rehabilitation session and generalized to everyday life activities., Conclusions: Such a system could well be integrated into a home based rehabilitation system.

Purpose: Virtual Reality (VR) platforms gained a lot of attention in the rehabilitation field due to their ability to engage patients and the opportunity they offer to use real world scenarios. As neglect is characterized by an impairment in exploring space that greatly affects daily living, VR could be a powerful tool compared to classical paper and pencil tasks and computer training. Nevertheless, available platforms are costly and obstructive. Here we describe a low cost platform for neglect rehabilitation, that using consumer equipments allows the patient to train at home in an intensive fashion., Method: We tested the platform on IB, a chronic neglect patient, who did not benefit from classical rehabilitation., Results: Our results show that IB improved both in terms of neglect and attention. Importantly, these ameliorations lasted at a follow up evaluation 5 months after the last treatment session and generalized to everyday life activities., Conclusions: VR platforms built using equipment technology and following theoretical principles on brain functioning may induce greater ameliorations in visuo-spatial deficits than classical paradigms possibly thanks to the real world scenarios in association with the "visual feedback" of the patient's own body operating in the virtual environment.

Support vector regression (SVR) is based on a linear combination of displaced replicas of the same function, called a kernel. When the function to be approximated is nonstationary, the single kernel approach may be ineffective, as it is not able to follow the variations in the frequency content in the different regions of the input space. The hierarchical support vector regression (HSVR) model presented here aims to provide a good solution also in these cases. HSVR consists of a set of hierarchical layers, each containing a standard SVR with Gaussian kernel at a given scale. Decreasing the scale layer by layer, details are incorporated inside the regression function. HSVR has been widely applied to noisy synthetic and real datasets and it has shown the ability in denoising the original data, obtaining an effective multiscale reconstruction of better quality than that obtained by standard SVR. Results also compare favorably with multikernel approaches. Furthermore, tuning the SVR configuration parameters is strongly simplified in the HSVR model.

In this paper, a novel real-time online network model is presented. It is derived from the hierarchical radial basis function (HRBF) model and it grows by automatically adding units at smaller scales, where the surface details are located, while data points are being collected. Real-time operation is achieved by exploiting the quasi-local nature of the Gaussian units: through the definition of a quad-tree structure to support their receptive field local network reconfiguration can be obtained. The model has been applied to 3-D scanning, where an updated real-time display of the manifold to the operator is fundamental to drive the acquisition procedure itself. Quantitative results are reported, which show that the accuracy achieved is comparable to that of two batch approaches: batch HRBF and support vector machines (SVMs). However, these two approaches are not suitable to real-time online learning. Moreover, proof of convergence is also given.

The analysis of neuron distribution inside the cerebral cortex is getting more and more attention. It allows assessing, for instance, age-related and pathological decay and preferential connections; moreover, it complements well studies on functional morphology aimed to discovering information coding in neuron assemblies. A large obstacle to these studies is the huge amount of time required by an operator to manually mark the single neurons. We present here an innovative solution for automaticize the entire process: starting from a set of tile images of a given cortical slice, the system stitches all the tiles together, identifies the grey areas and cover them with a mesh. Neurons are automatically identified and their local distribution determined. Key element of the method is a reliable neuron identification algorithm based on a novel multilayer shape analysis of the blobs identified in the tiles images. This allows identifying on average 87+/-6% of the total neurons in the slice, with a false positive ratio of 14+/-9%, in a relatively short processing time. The algorithm was tested on Nissl-stained cortical slices of the BA4 Human area, 10 microm thick, acquired as a meander of tiles ( approximately 3000 images for a slice of medium size) at 40 x magnification, which gives a resolution of 0.264 microm/pixel. Preliminary results on cortical lamination of Human BA4 area are reported. This method is the first automated algorithm for the analysis of a large high-resolution cortical slice.

The response of indirect x-ray digital imaging sensors is often not homogenous on the entire surface area. In this case, calibration is needed to build offset and gain maps, which are used to correct the sensor output. The sensors of new generation are equipped with an on-board memory, which serves to store these maps. However, because of its limited dimension, the maps have to be compressed before saving them. This step is critical because of the extremely high compression rate required. The authors propose here a novel method to achieve such a high compression rate, without degrading the quality of the sensor output. It is based on quad tree decomposition, which performs an adaptive sampling of the offset and gain maps, matched with a RBF-based interpolation strategy. The method was tested on a typical intraoral radiographic sensor and compared with traditional compression techniques. Qualitative and quantitative results show that the method achieves a higher compression rate and produces images of superior quality. The method can be adopted also in different fields where a high compression rate is required.

A new filter to restore radiographic images corrupted by impulsive noise is proposed. It is based on a switching scheme where all the pulses are first detected and then corrected through a median filter. The pulse detector is based on the hypothesis that the major contribution to image noise is given by the photon counting process, with some pixels corrupted by impulsive noise. Such statistics is described by an adequate mixture model. The filter is also able to reliably estimate the sensor gain. Its operation has been verified on both synthetic and real images; the experimental results demonstrate the superiority of the proposed approach in comparison with more traditional methods.

In this paper we introduce a simple model based on probabilistic finite state automata to describe an emotional interaction between a robot and a human user, or between simulated agents. Based on the agent's personality, attitude, and nature, and on the emotional inputs it receives, the model will determine the next emotional state displayed by the agent itself. The probabilistic and time-varying nature of the model yields rich and dynamic interactions, and an autonomous adaptation to the interlocutor. In addition, a reinforcement learning technique is applied to have one agent drive its partner's behavior toward desired states. The model may also be used as a tool for behavior analysis, by extracting high probability patterns of interaction and by resorting to the ergodic properties of Markov chains.

The purpose of the present study was to search for common patterns and for differences in climbing strategies in a group of recreational climbers. Twelve participants were involved in the study. Each participant climbed a simple indoor route consisting of a 3m horizontal shift followed by a 3m ascent for five times. Climbers could choose their own style, their preferred speed and holds. Their motion was recorded through motion capture based on passive markers. Results suggested that two main climbing strategies were used: the first preferring agility over force and the second preferring force over agility. We also found that our best climbers tried to minimize power during all trials.

Modern scanners are able to deliver huge quantities of three-dimensional (3-D) data points sampled on an object's surface, in a short time. These data have to be filtered and their cardinality reduced to come up with a mesh manageable at interactive rates. We introduce here a novel procedure to accomplish these two tasks, which is based on an optimized version of soft vector quantization (VQ). The resulting technique has been termed enhanced vector quantization (EVQ) since it introduces several improvements with respect to the classical soft VQ approaches. These are based on computationally expensive iterative optimization; local computation is introduced here, by means of an adequate partitioning of the data space called hyperbox (HB), to reduce the computational time so as to be linear in the number of data points N, saving more than 80% of time in real applications. Moreover, the algorithm can be fully parallelized, thus leading to an implementation that is sublinear in N. The voxel side and the other parameters are automatically determined from data distribution on the basis of the Zador's criterion. This makes the algorithm completely automatic. Because the only parameter to be specified is the compression rate, the procedure is suitable even for nontrained users. Results obtained in reconstructing faces of both humans and puppets as well as artifacts from point clouds publicly available on the web are reported and discussed, in comparison with other methods available in the literature. EVQ has been conceived as a general procedure, suited for VQ applications with large data sets whose data space has relatively low dimensionality.

A new real time filter for local exposure correction in panoramic radiographs is presented here. The filter, called PaRSEC, allows eliminating the exposure artifacts, mainly introduced by Automatic Exposure Control (AEC) systems. These artifacts reduce the image readability and its diagnostic utility. The PaRSEC filter operates a local exposure equalization, based on a reliable estimate of the column mean gray level. Qualitative and quantitative results are reported for typical panoramic radiographs. They show a complete removal of the artifacts. The method compares favorably with other classical methods targeted to exposure correction.

We present a new algorithm, called the soft-tissue filter, that can make both soft and bone tissue clearly visible in digital cephalic radiographies under a wide range of exposures. It uses a mixture model made up of two Gaussian distributions and one inverted lognormal distribution to analyze the image histogram. The image is clustered in three parts: background, soft tissue, and bone using this model. Improvement in the visibility of both structures is achieved through a local transformation based on gamma correction, stretching, and saturation, which is applied using different parameters for bone and soft-tissue pixels. A processing time of 1 s for 5 Mpixel images allows the filter to operate in real time. Although the default value of the filter parameters is adequate for most images, real-time operation allows adjustment to recover under- and overexposed images or to obtain the best quality subjectively. The filter was extensively clinically tested: quantitative and qualitative results are reported here.

An approximating neural model, called hierarchical radial basis function (HRBF) network, is presented here. This is a self-organizing (by growing) multiscale version of a radial basis function (RBF) network. It is constituted of hierarchical layers, each containing a Gaussian grid at a decreasing scale. The grids are not completely filled, but units are inserted only where the local error is over threshold. This guarantees a uniform residual error and the allocation of more units with smaller scales where the data contain higher frequencies. Only local operations, which do not require any iteration on the data, are required; this allows to construct the network in quasi-real time. Through harmonic analysis, it is demonstrated that, although a HRBF cannot be reduced to a traditional wavelet-based multiresolution analysis (MRA), it does employ Riesz bases and enjoys asymptotic approximation properties for a very large class of functions. HRBF networks have been extensively applied to the reconstruction of three-dimensional (3-D) models from noisy range data. The results illustrate their power in denoising the original data, obtaining an effective multiscale reconstruction of better quality than that obtained by MRA.

Regional cerebral blood flow (rCBF) PET scans were used to study the physiological bases of lipreading, a natural skill of extracting language from mouth movements, which contributes to speech perception in everyday life. Viewing connected mouth movements that could not be lexically identified and that evoke perception of isolated speech sounds (nonlexical lipreading) was associated with bilateral activation of the auditory association cortex around Wernicke's area, of left dorsal premotor cortex, and left opercular-premotor division of the left inferior frontal gyrus (Broca's area). The supplementary motor area was active as well. These areas have all been implicated in phonological processing, speech and mouth motor planning, and execution. In addition, nonlexical lipreading also differentially activated visual motion areas. Lexical access through lipreading was associated with a similar pattern of activation and with additional foci in ventral- and dorsolateral prefrontal cortex bilaterally and in left inferior parietal cortex. Linear regression analysis of cerebral blood flow and proficiency for lexical lipreading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lipreading from action representations that may differentiate lexical access from nonlexical processes.