Far Transfer Effects of Trainings on Executive Functions in Neurodevelopmental Disorders: A Systematic Review and Metanalysis.

Executive Functions are a set of interrelated, top-down processes essential for adaptive goal-directed behaviour, frequently impaired across different neurodevelopmental disorders with variable degrees of severity. Many executive-function-training studies in children with neurodevelopmental disorders have focused on near effects, investigating post-treatment improvements on directly trained processes, while enhancements of skills not directly trained, defined as far effects, are less considered, albeit these could be extremely relevant for reducing the negative impact of a disorder's core symptomatology. This systematic review and metanalysis aims to investigate the far effect outcomes after EF training in children with different types of neurodevelopmental disorders. 17 studies met the inclusion criteria for the systematic review, while 15 studies were selected in the metanalysis. An overall statistically significant effect size was found in the majority of far effect outcome measures considered in the studies. In particular, trainings on executive functions determine significant far effects on daily life functioning (0.46, 95% CI: [0.05-0.87]) and clinical symptoms (0.33, 95% CI: [0.15-0.51]). Despite a high variability of the results, intensity, frequency and the laboratory/life contexts dimension seem to be the most influential variables in determining far effects. This systematic review and metanalysis highlights the need to measure far effects of executive function training in neurodevelopmental disorders, selecting treatments not only on directly targeted processes, but also according to far impacts on the functional weakness of the disorder.

The Screening Hand Assessment for Infants for detecting the risk of unilateral cerebral palsy: Item selection and development.

AIM: To develop a screening tool (the screening Hand Assessment for Infants [s-HAI]) for infants aged from 3.5 months that can identify a high risk of developing unilateral cerebral palsy (CP) based on a selection of items from the HAI. METHOD: Receiver operating characteristic curve analysis was performed on previously collected HAI assessments from 212 infants (104 females, 108 males) aged from 3.5 to 8.5 months, to select items suitable for screening. The area under the curve (AUC), sensitivity, specificity, and cut-off values were derived for the suggested item combination. The clinical outcome (unilateral CP yes or no) at 24 months or older served as the external criterion. RESULTS: About half of the infants developed unilateral CP. The AUC across the items ranged from 0.63 to 0.80, and from 0.85 to 0.87 for different item combinations. Sensitivity for the selected 6-item set was 91% for 8 points or less and 88% for 7 points or less on the contralesional score of each hand, while specificity was 60% and 73% respectively. INTERPRETATION: The s-HAI, designed from six HAI items, has the potential to be used to screen infants at risk of unilateral CP from 3.5 months of age. It is easy to administer, time-efficient, and can be used in different settings. Its measurement properties and feasibility need to be tested in a new data set.

Wearable accelerometers for measuring and monitoring the motor behaviour of infants with brain damage during CareToy-Revised training.

BACKGROUND: Nowadays, wearable sensors are widely used to quantify physical and motor activity during daily life, and they also represent innovative solutions for healthcare. In the clinical framework, the assessment of motor behaviour is entrusted to clinical scales, but they are dependent on operator experience. Thanks to their intrinsic objectivity, sensor data are extremely useful to provide support to clinicians. Moreover, wearable sensors are user-friendly and compliant to be used in an ecological environment (i.e., at home). This paper aims to propose an innovative approach useful to predict clinical assessment scores of infants' motor activity. MATERIALS AND METHODS: Starting from data acquired by accelerometers placed on infants' wrists and trunk during playtime, we exploit the method of functional data analysis to implement new models combining quantitative data and clinical scales. In particular, acceleration data, transformed into activity indexes and combined with baseline clinical data, represent the input dataset for functional linear models. CONCLUSIONS: Despite the small number of data samples available, results show correlation between clinical outcome and quantitative predictors, indicating that functional linear models could be able to predict the clinical evaluation. Future works will focus on a more refined and robust application of the proposed method, based on the acquisition of more data for validating the presented models. TRIAL REGISTRATION NUMBER: ClincalTrials.gov; NCT03211533. Registered: July, 7th 2017. ClincalTrials.gov; NCT03234959. Registered: August, 1st 2017.

Predictive validity of the Hand Assessment for Infants in infants at risk of unilateral cerebral palsy.

AIM: To evaluate the sensitivity, specificity, and predictive value of the Hand Assessment for Infants (HAI) in identifying infants at risk of being diagnosed with unilateral cerebral palsy (CP), and to determine cut-off values for this purpose. METHOD: A convenience sample of 203 infants (106 females, 97 males) was assessed by the HAI at 3, 6, 9, and 12 months. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using receiver operating characteristic curve analysis. Cut-off values were derived for different ages. The clinical outcome (unilateral CP yes/no) at 24 months or more served as an external criterion to investigate the predictive validity of HAI. RESULTS: Half of the infants developed unilateral CP. The area under the curve ranged from 0.77 (95% CI [confidence interval] 0.63-0.91) to 0.95 (95% CI 0.90-1.00) across HAI scales and age intervals. Likewise, sensitivity ranged from 63% to 93%, specificity from 62% to 91%, and accuracy from 73% to 94%. INTERPRETATION: HAI scores demonstrated overall accuracy that ranged from very good to excellent in predicting unilateral CP in infants at risk aged between 3.5 and 12 months. This accuracy increased with age at assessment and the earliest possible prediction was at 3.5 months of age, when appropriate HAI cut-off values for different ages were applied. What this paper adds The Hand Assessment for Infants (HAI) predicts unilateral cerebral palsy (CP) with high accuracy. HAI cut-off values can guide clinical practice for early identification and diagnosis of unilateral CP.

Concurrent and predictive validity of the infant motor profile in infants at risk of neurodevelopmental disorders.

BACKGROUND: Preterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl's General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD. METHODS: 86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3 months corrected age (CA) using the GMA and at 5 months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18 months. RESULTS: Results confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman's ρ 0.76; p < .001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p < .001) and proves to be the strongest predictor of NDD (p < .001). The comparison of areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5 months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%). CONCLUSIONS: Early motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment. TRIAL REGISTRATION: NCT01990183 and NCT03234959 (clinicaltrials.gov).

Action observation training for rehabilitation in brain injuries: a systematic review and meta-analysis.

BACKGROUND: To systematically review and analyse the effects of Action Observation Training on adults and children with brain damage. METHODS: Seven electronic databases (Cochrane, EBSCO, Embase, Eric, PubMed, Scopus and Web of Science) were searched up to 16 September 2018 to select Randomized Controlled Trials focused on adults and children with brain damage that included AOT training on upper and/or lower limb carried out for at least 1 week. Identification of studies and data extraction was conducted with two reviewers working independently. Oxford Centre for Evidence-based Medicine (March2009) - Levels of Evidence and Physiotherapy Evidence Database scale were used to grade studies. The data collected from the articles were analysed using software R, version 3.4.3. Hedge's g values were calculated and effect size estimates were pooled across studies. Separate meta-analyses were carried out for each ICF domain (i.e. body function and activity) for upper and lower limb. RESULTS: Out of the 210 records identified after removing duplicates, 22 were selected for systematic review and 19 were included in the meta-analysis. Thirteen studies included in the meta-analysis focused on upper limb rehabilitation (4 in children and 9 in adults) and 6 on lower limb rehabilitation (only studies in adults). A total of 626 patients were included in the meta-analysis. An overall statistically significant effect size was found for upper limb body function (0.44, 95% CI: [0.24, 0.64], p < 0.001) and upper limb activity domain (0.47, 95% CI: [0.30, 0.64], p < 0.001). For lower limb, only the activity domain was analysed, revealing a statistically significant overall effect size (0.56, 95% CI: [0.28, 0.84], p < 0.001). CONCLUSIONS: Action Observation Training (AOT) is an innovative rehabilitation tool for individuals with brain damage, which shows promising results in improving the activity domain for upper and lower limbs, and also the body function domain for the upper limb. However, the examined studies lack uniformity and further well-designed, larger controlled trials are necessary to determine the most suitable type of AOT particularly in children. SYSTEMATIC REVIEW REGISTRATION: CRD42019119600.

Development of hand function during the first year of life in children with unilateral cerebral palsy.

AIM: To identify developmental trajectories of hand function in infants aged 3 months to 12 months with unilateral cerebral palsy (CP). METHOD: Infants at high risk of unilateral CP were recruited from 3 months of age from follow-up programmes and clinics in Sweden, the Netherlands, Italy, and Australia. Measurements on the Hand Assessment for Infants (HAI) were completed until 12 months of age. Group-based trajectory modelling was used to identify subgroups of infants with similar trajectories of development. Multinomial logistic regression determined associations between demographic variables and trajectory membership. RESULTS: Ninety-seven infants (52 males, 45 females; median gestational age 38wks [interquartile range 30-40wks]) were included. Infants were assessed between two and seven times (mean 4, SD 1.2) with a total of 387 observations. A three-group trajectory model identified a 'low-functioning group' (n=45: 46%), 'moderate-functioning group' (n=30: 31%), and 'high-functioning group' (n=22: 23%). Mean posterior probabilities (0.91-0.96) and odds of correct classification (26.3-33.2) indicated good model fit. Type of brain lesion, sex, side of hemiplegia, country, gestational age, and access to intensive intervention were not associated with group membership. INTERPRETATION: Three trajectories of hand function development for infants with unilateral CP were identified and indicate some greater distinctions between groups with increasing age. The HAI is a valuable measure, capturing development of hand function of infants with unilateral CP over time. WHAT THIS PAPER ADDS: Three distinct developmental trajectories of hand function in infants with unilateral cerebral palsy were identified. A low-functioning group made little progress in development of hand function in the first year of life. The degree of impairment on the impaired hand at 6 months of age is highly associated with trajectory membership. Infants with all types of brain lesion were represented across each trajectory group.

Hand Assessment for Infants: normative reference values.

AIM: To create normative reference values for unilateral and bilateral use of the hands, using the Hand Assessment for Infants (HAI), a newly developed criterion-referenced assessment measuring hand use in infants aged 3 months to 12 months at risk of cerebral palsy (CP). METHOD: In total, 489 HAI assessments of typically developing infants (243 females, 246 males), aged 3 months to 10 months (mean 6mo 14d [SD 2mo 5d]), were collected in Italy and Sweden. Normative growth curves based on mean and SDs were created, as well as skill acquisition curves for each test item. Correlation to age and differences between groups based on sex and nationality, as well as differences between the right and the left hand, were investigated. RESULTS: The growth curves showed a steady increase in mean value and a decrease in SD over age. There were no differences between groups based on sex or nationality. There was a negligible mean difference (0.1 raw score) between the right and left hands. INTERPRETATION: HAI normative reference values are now available, which can assist in identifying deviating hand use for each month of age, as well as a side difference between hands in infants at risk of CP. WHAT THIS PAPER ADDS: A Hand Assessment for Infants (HAI) result greater than 2SD below the mean indicates atypical hand use. Skill acquisition curves describe the age at which typically developing infants master the HAI items. Most typically developing infants do not demonstrate asymmetry in hand use.

EVALUACIÓN DE LA FUNCIÓN DE LA MANO PARA BEBÉS (HAI): VALORES NORMATIVOS DE REFERENCIA: OBJETIVO: Para crear valores de referencia normativos para el uso unilateral y bilateral de las manos, utilizando la Evaluación de la Mano para Infantes (HAI), una evaluación recientemente desarrollada basada en criterios que mide el uso de las manos en lactantes de 3 a 12 meses con riesgo de parálisis cerebral (PC). MÉTODO: En total, se recolectaron 489 evaluaciones usando el HAI de bebés con desarrollo típico (243 femeninos, 246 masculinos), de 3 a 10 meses (media 6 meses 14 días [DS 2 meses 5 días]), en Italia y Suecia. Se crearon curvas de crecimiento normativas basadas en la media y las desviaciones estándar, así como curvas de adquisición de habilidades para cada elemento de prueba. Se investigó la correlación con la edad y las diferencias entre grupos según el sexo y la nacionalidad, así como las diferencias entre la mano derecha y la mano izquierda. RESULTADOS: Las curvas de crecimiento mostraron un aumento constante en el valor medio y una disminución en el DE a lo largo de la edad. No hubo diferencias entre grupos por sexo o nacionalidad. Hubo una diferencia de medias insignificante (puntaje bruto de 0,1) entre las manos derecha e izquierda. INTERPRETACIÓN: Este estudio aporta los valores de referencia normativos de HAI, los cuales están disponibles, lo que puede ayudar a identificar la función de las manos que se desvía de los parámetros considerados como normales para cada mes de edad, así como una diferencia lateral entre las manos de los bebés en riesgo de PC.

AVALIAÇÃO DA MÃO PARA LACTENTES (AML): VALORES NORMATIVOS DE REFERÊNCIA: OBJETIVO: Criar valores normativos de referência para uso unilateral e bilateral das mãos, usando a Avaliação da mão para lactentes (AML), uma avaliação baseada em critérios que foi desenvolvida recentemente para mensurar o uso da mão em lactentes de 3 a 12 anos em risco para paralisia cerebral (PC). MÉTODO: No total, 489 avaliações da AML de lactentes com desenvolvimento típico (243 do sexo feminino, 246 do sexo masculino), com idades de 3 a 10 meses (média 6m 14d [DP 2m 5]), foram coletadas na Itália e na Suécia. Curvas normativas de crescimento baseadas em médias e desvios padrão foram criadas, assim como curvas de aquisição de habilidades para cada item do teste. Correlação com a idade e diferenças entre grupos baseadas no sexo e na nacionalidade, assim como diferenças entre mão direita e esquerda, foram investigadas. RESULTADOS As curvas de crescimento mostraram aumento contínuo na média e diminuição no DP com a idade. Não houve diferenças enter grupos com base no sexo ou nacionalidade. Houve uma diferença média inexpressiva (0,1 escore bruto) entre mãos direita e esquerda. INTERPRETAÇÃO: Valores normativos de referência da AML agora estão disponíveis, o que pode ajudar a identificar o uso anormal da mão para cada mês de vida, assim como diferenças entre lados em lactentes em risco para PC.

Effects on Parental Stress of Early Home-Based CareToy Intervention in Low-Risk Preterm Infants.

Parenting a preterm infant is more challenging than a full-term one. Parent involvement in early intervention programs seems to have positive psychosocial effects on both the child and parent. CareToy is an innovative smart system that provides an intensive individualized home-based family-centred EI in preterm infants between 3 and 9 age-corrected months. A RCT study, preceded by a pilot study, has been recently carried out to evaluate the effects of CareToy intervention on neurodevelopmental outcomes with respect to Standard Care. This study aims at evaluating the effects of CareToy early intervention on parenting stress in preterm infants. Parents (mother and father) of a subgroup of infants enrolled in the RCT filled out a self-report questionnaire on parenting stress (Parenting Stress Index-Short Form (PSI-SF)) before (T0) and after (T1) the CareToy or Standard Care period (4 weeks), according to the allocation of their preterm infant. For twins, an individual questionnaire for each one was filled out. Results obtained from mothers and fathers were separately analysed with nonparametric tests. 44 mothers and 44 fathers of 44 infants (24 CareToy/20 Standard Care) filled out the PSI-SF at T0 and at T1. CareToy intervention was mainly managed by mothers. A significant (p < 0.05) reduction in Parental Distress subscale in the CareToy group versus Standard Care was found in the mothers. No differences were found among the fathers. CareToy training seems to be effective in reducing parental distress in mothers, who spent more time on CareToy intervention. These findings confirm the importance of parental involvement in early intervention programs. This trial is registered with Clinical Trial.gov NCT01990183.

Actigraph assessment for measuring upper limb activity in unilateral cerebral palsy.

BACKGROUND: Detecting differences in upper limb use in children with unilateral cerebral palsy (UCP) is challenging and highly dependent on examiner experience. The recent introduction of technologies in the clinical environment, and in particular the use of wearable sensors, can provide quantitative measurement to overcome this issue. This study aims to evaluate ActiGraph GT3X+ as a tool for measuring asymmetry in the use of the two upper limbs (ULs) during the assessment with a standardized clinical tool, the Assisting Hand Assessment (AHA) in UCP patients aged 3-25 years compared to age-matched typically developing (TD) subjects. METHODS: Fifty children with UCP and 50 TD subjects were assessed with AHA while wearing ActiGraphs GT3X+ on both wrists. The mean activity of each hand (dominant and non-dominant, MADH and MANDH, respectively) and the asymmetry index (AI) were calculated. Two linear mixed model analyses were carried out to evaluate how dependent actigraphic variables (i.e. MANDH and AI) varied by group (TD vs UCP) and among levels of manual ability based on Manual Ability Classification System (MACS). In both models age, sex, side of hemiplegia, presence/absence of mirror movements were specified as random effects. RESULTS: The MANDH was significantly lower in UCP compared to TD, while the AI was significantly higher in UCP compared to TD. Moreover, in UCP group there were significant differences related to MACS levels, both for MANDH and AI. None of the random variables (i.e. age, sex, side, presence/absence of mirror movements) showed significant interaction with MANDH and AI. CONCLUSIONS: These results confirm that actigraphy could provide, in a standardized setting, a quantitative description of differences between upper limbs activity. TRIAL REGISTRATION: ClincalTrials.gov, NCT03054441 . Registered 15 February 2017.

Early intervention at home in infants with congenital brain lesion with CareToy revised: a RCT protocol.

BACKGROUND: Congenital brain lesions expose infants to be at high-risk for being affected by neurodevelopmental disorders such as cerebral palsy (CP). Early interventions programs can significantly impact and improve their neurodevelopment. Recently, in the framework of the European CareToy (CT) Project ( www.caretoy.eu ), a new medical device has been created to deliver an early, intensive, customized, intervention program, carried out at home by parents but remotely managed by expert and trained clinicians. Reviewing results of previous studies on preterm infants without congenital brain lesion, the CT platform has been revised and a new system created (CT-R). This study describes the protocol of a randomised controlled trial (RCT) aimed to evaluate, in a sample of infants at high-risk for CP, the efficacy of CT-R intervention compared to the Infant Massage (IM) intervention. METHODS/DESIGN: This RCT will be multi-centre, paired and evaluator-blinded. Eligible subjects will be preterm or full-term infants with brain lesions, in first year of age with predefined specific gross motor abilities. Recruited infants will be randomized into CT-R and IM groups at baseline (T0). Based on allocation, infants will perform an 8-week programme of personalized CareToy activities or Infant Massage. The primary outcome measure will be the Infant Motor Profile. On the basis of power calculation, it will require a sample size of 42 infants. Moreover, Peabody Developmental Motor Scales-Second Edition, Teller Acuity Cards, standardized video-recordings of parent-infant interaction and wearable sensors (Actigraphs) will be included as secondary outcome measures. Finally, parents will fill out questionnaires (Bayley Social-Emotional, Parents Stress Index). All outcome measures will be carried out at the beginning (T0) and at end of 8-weeks intervention period, primary endpoint (T1). Primary outcome and some secondary outcomes will be carried out also after 2 months from T1 and at 18 months of age (T2 and T3, respectively). The Bayley Cognitive subscale will be used as additional assessment at T3. DISCUSSION: This study protocol paper is the first study aimed to test CT-R system in infants at high-risk for CP. This paper will present the scientific background and trial methodology. TRIAL REGISTRATION: NCT03211533 and NCT03234959 ( www.clinicaltrials.gov ).

Combining constraint-induced movement therapy and action-observation training in children with unilateral cerebral palsy: a randomized controlled trial.

BACKGROUND: Upper limb (UL) deficits in children with unilateral cerebral palsy (uCP) have traditionally been targeted with motor execution treatment models, such as modified Constraint-Induced Movement Therapy (mCIMT). However, new approaches based on a neurophysiological model such as Action-Observation Training (AOT) may provide new opportunities for enhanced motor learning. The aim of this study is to describe a randomised controlled trial (RCT) protocol investigating the effects of an intensive treatment model, combining mCIMT and AOT compared to mCIMT alone on UL function in children with uCP. Additionally, the role of neurological factors as potential biomarkers of treatment response will be analysed. METHODS: An evaluator-blinded RCT will be conducted in 42 children aged between 6 and 12 years. Before randomization, children will be stratified according to their House Functional Classification Scale, age and type of corticospinal tract wiring. A 2-week day-camp will be set up in which children receive intensive mCIMT therapy for 6 hours a day on 9 out of 11 consecutive days (54 h) including AOT or control condition (15 h). During AOT, these children watch video sequences showing goal-directed actions and subsequently execute the observed actions with the more impaired UL. The control group performs the same actions after watching computer games without human motion. The primary outcome measure will be the Assisting Hand Assessment. Secondary outcomes comprise clinical assessments across body function, activity and participation level of the International Classification of Function, Disability and Health. Furthermore, to quantitatively evaluate UL movement patterns, a three-dimensional motion analysis will be conducted. UL function will be assessed at baseline, immediately before and after intervention and at 6 months follow up. Brain imaging comprising structural and functional connectivity measures as well as Transcranial Magnetic Stimulation (TMS) to evaluate corticospinal tract wiring will be acquired before the intervention. DISCUSSION: This paper describes the methodology of an RCT with two main objectives: (1) to evaluate the added value of AOT to mCIMT on UL outcome in children with uCP and (2) to investigate the role of neurological factors as potential biomarkers of treatment response. TRIAL REGISTRATION: NCT03256357 registered on 21st August 2017 (retrospectively registered).

Reorganization of the Action Observation Network and Sensory-Motor System in Children with Unilateral Cerebral Palsy: An fMRI Study.

Little is known about the action observation network (AON) in children with unilateral cerebral palsy (UCP). Using fMRI, we aimed to explore AON and sensory-motor network (SMN) in UCP children and compare them to typically developed (TD) children and analyse the relationship between AON (re-)organization and several neurophysiological and clinical measures. Twelve UCP children were assessed with clinical scales and transcranial magnetic stimulation (TMS). For the fMRI study, they underwent a paradigm based on observation of complex and simple object-manipulation tasks executed by dominant and nondominant hand. Moreover, UCP and TD children carried out a further fMRI session to explore SMN in both an active motor and passive sensory task. AON in the UCP group showed higher lateralization, negatively related to performances on clinical scales, and had greater activation of unaffected hemisphere as compared to the bilateral representation in the TD group. In addition, a good congruence was found between bilateral or contralateral activation of AON and activation of SMN and TMS data. These findings indicate that our paradigm might be useful in exploring AON and the response to therapy in UCP subjects.

Assessment of upper limb use in children with typical development and neurodevelopmental disorders by inertial sensors: a systematic review.

Understanding development of bimanual upper limb (UL) activities in both typical and atypical conditions in children is important for: i) tailoring rehabilitation programs, ii) monitoring progress, iii) determining outcomes and iv) evaluating effectiveness of treatment/rehabilitation. Recent technological advances, such as wearable sensors, offer possibilities to perform standard medical monitoring. Body-worn motion sensors, mainly accelerometers, have shown very promising results but, so far, these studies have mainly focused on adults. The main aim of this review was to report the evidence of UL activity of both typically developing (TD) children and children with neurodevelopmental disorders (NDDs) that are reliably reported and comparable, using a combination of multiple wearable inertial sensors, both in laboratory and natural settings. Articles were selected from three research databases (PubMed, Web of Science and EBSCO). Included studies reported data on children aged 0-20 years old simultaneously wearing at least two inertial sensors on upper extremities. The collected and reported data were relevant in order to describe the amount of physical activity performed by the two ULs separately. A total of 21 articles were selected: 11 including TD, and 10 regarding NDDs. For each article, a review of both clinical and technical data was performed. We considered inertial sensors used for following aims: (i) to establish activity intensity cut-points; (ii) to investigate validity and reliability of specified markers, placement and/or number of inertial sensors; (iii) to evaluate duration and intensity of natural UL movements, defined motor tasks and tremor; and (iv) to assess efficacy of certain rehabilitation protocols. Our conclusions were that inertial sensors are able to detect differences in use between both hands and that all reviewed studies support use of accelerometers as an objective outcome measure, appropriate in assessing UL activity in young children with NDDs and determining intervention effectiveness. Further research on responsiveness to interventions and consistency with use in real-world settings is needed. This information could be useful in planning UL rehabilitation strategies.

Development of the Hand Assessment for Infants: evidence of internal scale validity.

AIM: The aim of this study was to develop a descriptive and evaluative assessment of upper limb function for infants aged 3 to 12 months and to investigate its internal scale validity for use with infants at risk of unilateral cerebral palsy. METHOD: The concepts of the test items and scoring criteria were developed. Internal scale validity and aspects of reliability were investigated on the basis of 156 assessments of infants at 3 to 12 months corrected age (mean 7.2mo, SD 2.5) with signs of asymmetric hand use. Rasch measurement model analysis and non-parametric statistics were used. RESULTS: The new test, the Hand Assessment for Infants (HAI), consists of 12 unimanual and five bimanual items, each scored on a 3-point rating scale. It demonstrated a unidimensional construct and good fit to the Rasch model requirements. The excellent person reliability enabled person separation to six significant ability strata. The HAI produced an interval-level measure of bilateral hand use as well as unimanual scores of each hand, allowing a quantification of possible asymmetry expressed as an asymmetry index. INTERPRETATION: The HAI can be considered a valid assessment tool for measuring bilateral hand use and quantifying side difference between hands among infants at risk of developing unilateral cerebral palsy. WHAT THIS PAPER ADDS: The Hand Assessment for Infants (HAI) measures the use of both hands and quantifies a possible asymmetry of hand use. HAI is valid for infants at 3 to 12 months corrected age at risk of unilateral cerebral palsy.

Action observation network in childhood: a comparative fMRI study with adults.

Very little is known about the action observation network and the mirror neuron system (AON/MNS) in children and its age-related properties compared with those observed in adults. In the present fMRI study we explored the activation of areas belonging to the AON/MNS in children and adults during observation of complex hand-grasping actions, as compared to observation of simple grasping acts executed with the left and the right hand, seen from a first person perspective. The results indicate that during the action observation tasks in children there was activation of a cortical network similar to that found in adults, including the premotor cortex, the posterior part of the inferior frontal gyrus and the posterior parietal lobe. However, the activation in children was more widespread and showed a higher inter-subject variability compared with adults. Furthermore, the activated network seems more lateralized to the left hemisphere in adults and more bilateral in children, with a linear growth of lateralization index as a function of age. Finally, in children the activation in the anterior intraparietal cortex (AIP) of each hemisphere was higher during observation of the contralateral hand (hand identity effect) and during the observation of complex actions relative to simple grasping acts, confirming the role of AIP for action-related hand identity previously described in adults. These results support the assumption that structure and size of action representations are sensitive to mechanisms of development and show physiological plasticity. These properties of the AON/MNS could constitute a powerful tool for spontaneous reorganization and recovery of motor deficits after brain injury in children and in adults, as well as for specific rehabilitation programmes.

Early intervention in neurodevelopmental disorders: underlying neural mechanisms.

Neurodevelopmental disorders affect motor, cognitive, language, learning, and behavioural development with lifelong consequences. Early identification of infants at risk for neurodevelopmental disorders is a major prerequisite for intervention programmes. This ensures that interventions which aim to positively modify the natural history of these disorders can start in the first weeks or months of life. As indicated by recent scientific evidence, gene abnormalities or congenital brain lesions are not the sole determinants for the neurodevelopmental outcome of affected infants. In fact, environment and experience may modify brain development and improve the outcome in infants at risk for neurodevelopmental disorders. In this review, we analyse the complexity and sensitivity of the brain to environmental stimuli, highlighting clinical effects of early intervention, mainly reported so far in preterm infants, and summarizing the effects of enriched environment on human and animal models. Finally, we discuss some new approaches to early intervention, based on recent neurophysiological theories and new breakthroughs in biotechnologies for diagnosis and rehabilitation.

A new system for quantitative evaluation of infant gaze capabilities in a wide visual field.

BACKGROUND: The visual assessment of infants poses specific challenges: many techniques that are used on adults are based on the patient's response, and are not suitable for infants. Significant advances in the eye-tracking have made this assessment of infant visual capabilities easier, however, eye-tracking still requires the subject's collaboration, in most cases and thus limiting the application in infant research. Moreover, there is a lack of transferability to clinical practice, and thus it emerges the need for a new tool to measure the paradigms and explore the most common visual competences in a wide visual field. This work presents the design, development and preliminary testing of a new system for measuring infant's gaze in the wide visual field called CareToy C: CareToy for Clinics. METHODS: The system is based on a commercial eye tracker (SmartEye) with six cameras running at 60 Hz, suitable for measuring an infant's gaze. In order to stimulate the infant visually and audibly, a mechanical structure has been designed to support five speakers and five screens at a specific distance (60 cm) and angle: one in the centre, two on the right-hand side and two on the left (at 30° and 60° respectively). Different tasks have been designed in order to evaluate the system capability to assess the infant's gaze movements during different conditions (such as gap, overlap or audio-visual paradigms). Nine healthy infants aged 4-10 months were assessed as they performed the visual tasks at random. RESULTS: We developed a system able to measure infant's gaze in a wide visual field covering a total visual range of ±60° from the centre with an intermediate evaluation at ±30°. Moreover, the same system, thanks to different integrated software, was able to provide different visual paradigms (as gap, overlap and audio-visual) assessing and comparing different visual and multisensory sub-competencies. The proposed system endowed the integration of a commercial eye-tracker into a purposive setup in a smart and innovative way. CONCLUSIONS: The proposed system is suitable for measuring and evaluating infant's gaze capabilities in a wide visual field, in order to provide quantitative data that can enrich the clinical assessment.

Home-based, early intervention with mechatronic toys for preterm infants at risk of neurodevelopmental disorders (CARETOY): a RCT protocol.

BACKGROUND: Preterm infants are at risk for neurodevelopmental disorders, including motor, cognitive or behavioural problems, which may potentially be modified by early intervention. The EU CareToy Project Consortium (http://www.caretoy.eu) has developed a new modular system for intensive, individualized, home-based and family-centred early intervention, managed remotely by rehabilitation staff. A randomised controlled trial (RCT) has been designed to evaluate the efficacy of CareToy training in a first sample of low-risk preterm infants. METHODS/DESIGN: The trial, randomised, multi-center, evaluator-blinded, parallel group controlled, is designed according to CONSORT Statement. Eligible subjects are infants born preterm without major complications, aged 3-9 months of corrected age with specific gross-motor abilities defined by Ages & Stages Questionnaire scores. Recruited infants, whose parents will sign a written informed consent for participation, will be randomized in CareToy training and control groups at baseline (T0). CareToy group will perform four weeks of personalized activities with the CareToy system, customized by the rehabilitation staff. The control group will continue standard care. Infant Motor Profile Scale is the primary outcome measure and a total sample size of 40 infants has been established. Bayley-Cognitive subscale, Alberta Infants Motor Scale and Teller Acuity Cards are secondary outcome measures. All measurements will be performed at T0 and at the end of training/control period (T1). For ethical reasons, after this first phase infants enrolled in the control group will perform the CareToy training, while the training group will continue standard care. At the end of open phase (T2) all infants will be assessed as at T1. Further assessment will be performed at 18 months corrected age (T3) to evaluate the long-term effects on neurodevelopmental outcome. Caregivers and rehabilitation staff will not be blinded whereas all the clinical assessments will be performed, videotaped and scored by blind assessors. The trial is ongoing and it is expected to be completed by April 2015. DISCUSSION: This paper describes RCT methodology to evaluate CareToy as a new tool for early intervention in preterm infants, first contribution to test this new type of system. It presents background, hypotheses, outcome measures and trial methodology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01990183. EU grant ICT-2011.5.1-287932.

Pathways to democratized healthcare: Envisioning human-centered AI-as-a-service for customized diagnosis and rehabilitation.

The ongoing digital revolution in the healthcare sector, emphasized by bodies like the US Food and Drug Administration (FDA), is paving the way for a shift towards person-centric healthcare models. These models consider individual needs, turning patients from passive recipients to active participants. A key factor in this shift is Artificial Intelligence (AI), which has the capacity to revolutionize healthcare delivery due to its ability to personalize it. With the rise of software in healthcare and the proliferation of the Internet of Things (IoT), a surge of digital data is being produced. This data, alongside improvements in AI's explainability, is facilitating the spread of person-centric healthcare models, aiming at improving health management and patient experience. This paper outlines a human-centered methodology for the development of an AI-as-a-service platform with the goal of broadening access to personalized healthcare. This approach places humans at its core, aiming to augment, not replace, human capabilities and integrate in current processes. The primary research question guiding this study is: "How can Human-Centered AI principles be considered when designing an AI-as-a-service platform that democratizes access to personalized healthcare?" This informed both our research direction and investigation. Our approach involves a design fiction methodology, engaging clinicians from different domains to gather their perspectives on how AI can meet their needs by envisioning potential future scenarios and addressing possible ethical and social challenges. Additionally, we incorporate Meta-Design principles, investigating opportunities for users to modify the AI system based on their experiences. This promotes a platform that evolves with the user and considers many different perspectives.