Asymmetry in sleep spindles and motor outcome in infants with unilateral brain injury.

AIM: To determine whether interhemispheric difference in sleep spindles in infants with perinatal unilateral brain injury could link to a pathological network reorganization that underpins the development of unilateral cerebral palsy (CP). METHOD: This was a multicentre retrospective study of 40 infants (19 females, 21 males) with unilateral brain injury. Sleep spindles were detected and quantified with an automated algorithm from electroencephalograph records performed at 2 months to 5 months of age. The clinical outcomes after 18 months were compared to spindle power asymmetry (SPA) between hemispheres in different brain regions. RESULTS: We found a significantly increased SPA in infants who later developed unilateral CP (n=13, with the most robust interhemispheric difference seen in the central spindles. The best individual-level prediction of unilateral CP was seen in the centro-occipital spindles with an overall accuracy of 93%. An empiric cut-off level for SPA at 0.65 gave a positive predictive value of 100% and a negative predictive value of 93% for later development of unilateral CP. INTERPRETATION: Our data suggest that automated analysis of interhemispheric SPA provides a potential biomarker of unilateral CP at a very early age. This holds promise for guiding the early diagnostic process in infants with a perinatally identified brain injury. WHAT THIS PAPER ADDS: Unilateral perinatal brain injury may affect the development of electroencephalogram (EEG) sleep spindles. Interhemispheric asymmetry in sleep spindles can be quantified with automated EEG analysis. Spindle power asymmetry can be a potential biomarker of unilateral cerebral palsy.

Early clinical and MRI biomarkers of cognitive and motor outcomes in very preterm born infants.

BACKGROUND: This study aimed to identify which MRI and clinical assessments, alone or in combination, from (i) early (32 weeks postmenstrual age, PMA), (ii) term equivalent age (TEA) and (iii) 3 months corrected age (CA) are associated with motor or cognitive outcomes at 2 years CA in infants born <31 weeks gestation. METHODS: Prospective cohort study of 98 infants who underwent early and TEA MRI (n = 59 males; median birth gestational age 28 + 5 weeks). Hammersmith Neonatal Neurological Examination (HNNE), NICU Neonatal Neurobehavioural Scale and General Movements Assessment (GMs) were performed early and at TEA. Premie-Neuro was performed early and GMs, Test of Infant Motor Performance and visual assessment were performed at TEA and 3 months CA. Neurodevelopmental outcomes were determined using Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: The best combined motor outcome model included 3-month GMs (ß = -11.41; 95% CI = -17.34, -5.49), TEA MRI deep grey matter score (ß = -6.23; 95% CI = -9.47, -2.99) and early HNNE reflexes (ß = 3.51; 95% CI = 0.86, 6.16). Combined cognitive model included 3-month GMs (ß = -10.01; 95% CI = -15.90, -4.12) and TEA HNNE score (ß = 1.33; 95% CI = 0.57, 2.08). CONCLUSION: Early neonatal neurological assessment improves associations with motor outcomes when combined with term MRI and 3-month GMs. Term neurological assessment combined with 3-month GMs improves associations with cognitive outcomes. IMPACT: We present associations between 32- and 40-week MRI, comprehensive clinical assessments and later 2-year motor and cognitive outcomes for children born <31 weeks gestation. MRI and clinical assessment of motor, neurological and neurobehavioural function earlier than term equivalent age in very preterm infants is safe and becoming more available in clinical settings. Most of these children are discharged from hospital before term age and so completing assessments prior to discharge can assist with follow up. MRI and neurological assessment prior to term equivalent age while the child is still in hospital can provide earlier identification of children at highest risk of adverse outcomes and guide follow-up screening and intervention services.

Protocol of changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with bilateral cerebral palsy: a multisite randomized controlled trial.

BACKGROUND: Cerebral palsy (CP), which is the leading cause of motor disability during childhood, can produce sensory and cognitive impairments at different degrees. Most recent therapeutic interventions for these patients have solely focused on upper extremities (UE), although more than 60% of these patients present lower extremities (LE) deficits. Recently, a new therapeutic concept, Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE), has been proposed, involving the constant stimulation of UE and LE. Based on motor skill learning principles, HABIT-ILE is delivered in a day-camp setting, promoting voluntary movements for several hours per day during 10 consecutive week days. Interestingly, the effects of this intervention in a large scale of youngsters are yet to be observed. This is of interest due to the lack of knowledge on functional, neuroplastic and biomechanical changes in infants with bilateral CP. The aim of this randomized controlled study is to assess the effects of HABIT-ILE adapted for pre-school children with bilateral CP regarding functional, neuroplastic and biomechanical factors. METHODS: This international, multicentric study will include 50 pre-school children with CP from 12 to 60 months of age, comparing the effect of 50 h (2 weeks) of HABIT-ILE versus regular motor activity and/or customary rehabilitation. HABIT-ILE presents structured activities and functional tasks with continuous increase in difficulty while the child evolves. Assessments will be performed at 3 period times: baseline, two weeks later and 3 months later. The primary outcome will be the Gross Motor Function Measure 66. Secondary outcomes will include Both Hands Assessment, Melbourne Assessment-2, Semmes-Weinstein Monofilament Test, algometry assessments, executive function tests, ACTIVLIM-CP questionnaire, Pediatric Evaluation of Disability Inventory (computer adaptative test), Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, neuroimaging and kinematics. DISCUSSION: The results of this study should highlight the impact of a motor, intensive, goal-directed therapy (HABIT-ILE) in pre-school children at a functional, neuroplastic and biomechanical level. In addition, this changes could demonstrated the impact of this intervention in the developmental curve of each child, improving functional ability, activity and participation in short-, mid- and long-term. NAME OF THE REGISTRY: Evaluation of Functional, Neuroplastic and Biomechanical Changes Induced by an Intensive, Playful Early-morning Treatment Including Lower Limbs (EARLY-HABIT-ILE) in Preschool Children With Uni and Bilateral Cerebral Palsy (HABIT-ILE). TRIAL REGISTRATION: NCT04017871 REGISTRATION DATE: July 12, 2019.

Visual Function Classification System for children with cerebral palsy: development and validation.

AIM: To develop and validate the Visual Function Classification System (VFCS), which was created to classify how children with cerebral palsy (CP) use visual abilities in daily life. METHOD: The process of development and validation of the VFCS involved four phases: (1) drafting of the five levels from the analysis of literature and clinical experience; (2) validation of constructs and revision of the levels for concept meaningfulness, using nominal group process; (3) refinement by international Delphi survey; and(4) assessment of interrater reliability among professionals and with caregivers, and of test-retest reliability. RESULTS: Five nominal groups involved 29 participants; 65 people completed the first round and 51 the second round of the Delphi survey. Construct validity was demonstrated within an expert group and external validation through several stakeholders, with the involvement of patients and families to ensure meaningfulness of the concept. Discussions continued until consensus was reached about the construct and content of the five levels. Participants in the reliability study included 29 professionals, 39 parents, and a total sample of 160 children with CP (mean age [SD] 6y 6mo [3y 4mo]; median 5y 7mo, range 1-19y). Absolute interrater agreement among professionals was 86% (weighted κ=0.88; 95% confidence interval [CI] 0.83-0.93). Test-retest reliability was high (weighted κ=0.97; 95% CI 0.95-0.99). Parent-professional interrater reliability on 39 children was moderate (weighted κ=0.51; 95% CI 0.39-0.63). INTERPRETATION: The VFCS has been appropriately constructed and provides a reliable system to classify visual abilities of children with CP both in clinical and in research settings. WHAT THIS PAPER ADDS: The Visual Function Classification System is a valid and reliable system. It classifies visual abilities of children with cerebral palsy in clinical and research settings. At a clinical level, it can be used to harmonize communication among professionals and identify patients' strengths and weaknesses. In research settings, it can be used to stratify patients, define natural history evolution, and interpret intervention studies.

SISTEMA DE CLASIFICACIÓN DE LA FUNCIÓN VISUAL PARA NIÑOS CON PARÁLISIS CEREBRAL: DESARROLLO Y VALIDACIÓN: OBJETIVO: Desarrollar y validar el Sistema de Clasificación de la Función Visual (VFCS, siglas en inglés), que fue creado para clasificar cómo los niños con parálisis cerebral (PC) usan las habilidades visuales en la vida diaria. MÉTODO: El proceso de desarrollo y validación del VFCS involucró cuatro fases: (1) elaboración de los cinco niveles a partir del análisis de la literatura y la experiencia clínica; (2) la validación de constructos y la revisión de los niveles para el significado de los conceptos, utilizando un proceso de grupo nominal; (3) refinamiento por encuesta internacional de Delphi; (4) evaluación de la confiabilidad entre evaluadores entre profesionales y con los cuidadores, y de confiabilidad de prueba y reevaluación RESULTADOS: Cinco grupos nominales incluyeron 29 participantes; 65 personas completaron la primera ronda y 51 la segunda ronda de la encuesta de Delphi. La validez de constructo se demostró dentro de un grupo de expertos y una validación externa a través de varias partes interesadas, con la participación de los pacientes y las familias para garantizar el significado del concepto. Las discusiones continuaron hasta que se llegó a un consenso sobre el constructo y el contenido de los cinco niveles. Los participantes en el estudio de confiabilidad incluyeron 29 profesionales, 39 padres y una muestra total de 160 niños con PC (edad media [DS] 6 años 6 meses [3 años 4 meses]; mediana 5 años 7 meses, rango 1-19 años). El acuerdo de evaluador absoluto entre profesionales fue del 86% (κ ponderada = 0,88; intervalo de confianza del 95% [IC] 0,83-0,93). La fiabilidad de Test-Retest fue alta (κ ponderada = 0,97; IC del 95%: 0,95 a 0,99). La confiabilidad entre los padres y profesionales entre 39 niños fue moderada (ponderada κ = 0,51; IC del 95%: 0,39 a 0,63). INTERPRETACIÓN: El VFCS se ha construido de manera adecuada y proporciona un sistema confiable para clasificar las habilidades visuales de los niños con PC, tanto en el ámbito clínico como en el de investigación.

SISTEMA DE CLASSIFICAÇÃO DA FUNÇÃO VISUAL PARA CRIANÇAS COM PARALISIA CEREBRAL: DESENVOLVIMENTO E VALIDAÇÃO: OBJETIVO: Desenvolver e validar o Sistema de Classificação da Função Visual (SCFV), que foi criado para classificar como crianças com paralisia cerebral (PC) usam capacidades visuais na vida diária. MÉTODO: O processo de desenvolvimento e validação do SCFV envolve quatro fases: (1) rascunho dos cinco níveis a partir da análise da literatura e experiência clínica; (2) validação de construtos e revisão dos níveis de significância dos conceitos, usando processo nominal de grupos; (3) refinamento por meio de levantamento Delphi internacional; (4) avaliação da confiabilidade inter-examinadores entre profissionais e cuidadores, e confiabilidade teste-reteste. RESULTADOS: Cinco grupos nominais envolveram 29 participantes; 65 pessoas completaram a primeira rodada e 51 a segunda rodada do levantamento Delphi. A validade de constructo foi demonstrada em um grupo de especialistas, e a validade externa por meio de vários interessados, com envolvimento de pacientes e famílias para assegurar a significância do conceito. As discussões continuaram até que fosse atingido consenso sobre o constructo e o conteúdo dos cinco níveis. Os participantes no estudo de confiabilidade incluíram 29 profissionais, 39 pais e uma amostra total de 160 crianças com PC (média de idade [DP] 6a 6m [3a 4m]; mediana 5a 7m, variação 1-19a). A confiabilidade inter-examinadores absoluta entre profissionais foi 86% (κ ponderado=0,88; intervalo de confiança [IC] a 95% 0,83-0,93). A confiabilidade teste-reteste foi alta (κ ponderado =0,97; IC 95% 0,95-0,99). A confiabilidade inter-examinadores pais-profissionais em 39 crianças foi moderada (κ ponderado =0,51; IC 95% 0,39-0,63). INTERPRETAÇÃO: O SCFV foi elaborado apropriadamente e é um sistema confiável para classificar as capacidades visuais de crianças com PC em ambientes clínicos e acadêmicos.

Psychometric Properties of the General Movement Optimality Score using Rasch Measurement.

AIM: To explore the psychometric properties of the general movements optimality score (GMOS) by examining its dimensionality, rating scale functioning, and item hierarchies using Rasch measurement. METHODS: Secondary data analysis of the GMOS data for video-recording of 383 infants with uni-, multidimensional, and mixed Rasch partial credit models. Videos were scored based on the global General Movement Assessment categories, and on the amplitude, speed, spatial range, proximal and distal rotations, onset and offset, tremulous and cramped components of the upper and lower extremities (21 items), resulting in the GMOS. RESULTS: The GMOS data fits best to a unidimensional mixed Rasch model with three different classes of infants, with all but two items contributing to the infants' separation. Rating scales functioned well for 19 items. Item difficulty hierarchies varied depending on infants' class. No floor effect and no substantive gaps between item difficulty estimates were found. CONCLUSION: The GMOS has strong psychometric properties to distinguish infants with different functional motor performance and provides a quantitative measure of quality of movement. INTERPRETATION: The GMOS can be confidently used to assist with early diagnosis, grade motor performance, and provide a solid base to study individual general movement developmental trajectories.

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.

Automated pose estimation captures key aspects of General Movements at eight to 17 weeks from conventional videos.

AIM: General movement assessment requires substantial expertise for accurate visual interpretation. Our aim was to evaluate an automated pose estimation method, using conventional video records, to see if it could capture infant movements using objective biomarkers. METHODS: We selected archived videos from 21 infants aged eight to 17 weeks who had taken part in studies at the IRCCS Fondazione Stella Maris (Italy), from 2011 to 2017. Of these, 14 presented with typical low-risk movements, while seven presented with atypical movements and were later diagnosed with cerebral palsy. Skeleton videos were produced using a computational pose estimation model adapted for infants and these were blindly assessed to see whether they contained the information needed for classification by human experts. Movements of skeletal key points were analysed using kinematic metrics to provide a biomarker to distinguish between groups. RESULTS: The visual assessments of the skeleton videos were very accurate, with Cohen's K of 0.90 when compared with the classification of conventional videos. Quantitative analysis showed that arm movements were more variable in infants with typical movements. CONCLUSION: It was possible to extract automated estimation of movement patterns from conventional video records and convert them to skeleton footage. This could allow quantitative analysis of existing footage.

Early Intervention to Improve Sucking in Preterm Newborns: A Systematic Review of Quantitative Studies.

BACKGROUND: Premature birth is associated with feeding difficulties due to inadequate coordination of sucking, swallowing, and breathing. Nonnutritive sucking (NNS) and oral stimulation interventions may be effective for oral feeding promotion, but the mechanisms of the intervention effects need further clarifications. PURPOSE: We reviewed preterm infant intervention studies with quantitative outcomes of sucking performance to summarize the evidence of the effect of interventions on specific components of sucking. METHODS: PubMed, CINAHL, MEDLINE, EMBASE, and PSYCOLIST databases were searched for English language publications through August 2017. Studies were selected if they involved preterm infants, tested experimental interventions to improve sucking or oral feeding skills, and included outcome as an objective measure of sucking performance. Specific Medical Subject Headings (MeSH) terms were utilized. RESULTS: Nineteen studies were included in this review: 15 randomized, 1 quasi-randomized, and 3 crossover randomized controlled trials. Intervention types were grouped into 6 categories (i) NNS, (ii) NNS with auditory reinforcement, (iii) sensorimotor stimulation, (iv) oral support, (v) combined training, and (vi) nutritive sucking. Efficiency parameters were positively influenced by most types of interventions, though appear to be less affected by trainings based on NNS alone. IMPLICATIONS FOR PRACTICE: These findings may be useful in the clinical care of infants requiring support to achieve efficient sucking skills through NNS and oral stimulation interventions. IMPLICATIONS FOR RESEARCH: Further studies including quantitative measures of sucking performance outcome measures are needed in order to best understand the needs and provide more tailored interventions to preterm infants.

Potentials of Ultrahigh-Field MRI for the Study of Somatosensory Reorganization in Congenital Hemiplegia.

Reorganization of somatosensory function influences the clinical recovery of subjects with congenital unilateral brain lesions. Ultrahigh-field (UHF) functional MRI (fMRI) with the use of a 7 T magnet has the potential to contribute fundamentally to the current knowledge of such plasticity mechanisms. The purpose of this study was to obtain preliminary information on the possible advantages of the study of somatosensory reorganization at UHF fMRI. We enrolled 6 young adults (mean age 25 ± 6 years) with congenital unilateral brain lesions (4 in the left hemisphere and 2 in the right hemisphere; 4 with perilesional motor reorganization and 2 with contralesional motor reorganization) and 7 healthy age-matched controls. Nondominant hand sensory assessment included stereognosis and 2-point discrimination. Task-dependent fMRI was performed to elicit a somatosensory activation by using a safe and quantitative device developed ad hoc to deliver a reproducible gentle tactile stimulus to the distal phalanx of thumb and index fingers. Group analysis was performed in the control group. Individual analyses in the native space were performed with data of hemiplegic subjects. The gentle tactile stimulus showed great accuracy in determining somatosensory cortex activation. Single-subject gentle tactile stimulus showed an S1 activation in the postcentral gyrus and an S2 activation in the inferior parietal insular cortex. A correlation emerged between an index of S1 reorganization (distance between expected and reorganized S1) and sensory deficit (p < 0.05) in subjects with hemiplegia, with higher distance related to a more severe sensory deficit. Increase in spatial resolution at 7 T allows a better localization of reorganized tactile function validated by its correlation with clinical measures. Our results support the S1 early-determination hypothesis and support the central role of topography of reorganized S1 compared to a less relevant S1-M1 integration.

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.

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.

Action observation in infancy: implications for neuro-rehabilitation.

Action observation therapy has been found to be effective in improving hand motor function in both adults with stroke and children with unilateral cerebral palsy. We here propose a provocative hypothesis arguing that the same therapy might be effective in very early intervention in infants with unilateral or asymmetric brain damage, but through a different underlying mechanism. If the activation of motor networks induced in infancy by action observation enhances the excitability of the damaged sensorimotor cortex, it could also accelerate the maturation of the corticospinal tract and the adaptive shaping of the spinal motor circuits. This hypothesis should be explored carefully in prospective studies and, if confirmed, might support the use of action observation therapy at a much earlier time than experimented so far.

Do mirror movements relate to hand function and timing of the brain lesion in children with unilateral cerebral palsy?

AIM: This study aimed to systematically map the severity of mirror movements in both hands in a prospective cohort of children with unilateral cerebral palsy, and to explore the relationship with hand function and brain lesion type. METHOD: Seventy-eight children were included (41 males, 37 females; age 9y 4mo, SD 3y 1mo, range 5-15y). Mirror movements were scored during three repetitive tasks following Woods and Teuber criteria. Strength, tone, Melbourne Assessment, Jebsen-Taylor test, and Assisting Hand Assessment were evaluated. Lesions were classified into malformations (n=5), periventricular (n=43), cortico-subcortical (n=22), and postnatally acquired lesions (n=8). RESULTS: Significantly more mirror movements were observed in the non-paretic versus the paretic hand (p≤0.003). Higher mirror movement scores in the non-paretic hand significantly correlated with lower distal strength and lower scores on unimanual and bimanual assessments (r=0.29-0.41). In the paretic hand, significant differences were found between lesion types (p=0.03). INTERPRETATION: The occurrence of mirror movements in the non-paretic hand seems related to hand function while mirror movements in the paretic hand seem more related to the lesion timing, whereby children with earlier lesions present with more mirror movements.

PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants.

BACKGROUND: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured. METHODS/DESIGN: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. DISCUSSION: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012.

Optimization of MRI-based scoring scales of brain injury severity in children with unilateral cerebral palsy.

BACKGROUND: Several scoring systems for measuring brain injury severity have been developed to standardize the classification of MRI results, which allows for the prediction of functional outcomes to help plan effective interventions for children with cerebral palsy. OBJECTIVE: The aim of this study is to use statistical techniques to optimize the clinical utility of a recently proposed template-based scoring method by weighting individual anatomical scores of injury, while maintaining its simplicity by retaining only a subset of scored anatomical regions. MATERIALS AND METHODS: Seventy-six children with unilateral cerebral palsy were evaluated in terms of upper limb motor function using the Assisting Hand Assessment measure and injuries visible on MRI using a semiquantitative approach. This cohort included 52 children with periventricular white matter injury and 24 with cortical and deep gray matter injuries. A subset of the template-derived cerebral regions was selected using a data-driven region selection algorithm. Linear regression was performed using this subset, with interaction effects excluded. RESULTS: Linear regression improved multiple correlations between MRI-based and Assisting Hand Assessment scores for both periventricular white matter (R squared increased to 0.45 from 0, P < 0.0001) and cortical and deep gray matter (0.84 from 0.44, P < 0.0001) cohorts. In both cohorts, the data-driven approach retained fewer than 8 of the 40 template-derived anatomical regions. CONCLUSION: The equal or better prediction of the clinically meaningful Assisting Hand Assessment measure using fewer anatomical regions highlights the potential of these developments to enable enhanced quantification of injury and prediction of patient motor outcome, while maintaining the clinical expediency of the scoring approach.

Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

Cognitive strategies for locomotor navigation in normal development and cerebral palsy.

Visual-spatial impairment is a fundamental disorder in cerebral palsy (CP). However, current spatial testing is restricted to reaching space, whereas navigational space is seldom assessed. The Magic Carpet test, derived from the Corsi Block-tapping Task (CBT) for visual-spatial memory, is a new developmental test for navigation. The performances of the Magic Carpet test and CBT were assessed in 17 children with unilateral and bilateral spastic CP. The results were compared with an equal number of typically developing children, matched for age and sex. Magnetic resonance imaging scans of children with CP were scored according to a newly validated semi-quantitative classification. CBT span was significantly lower in CP, especially in bilateral forms, than in the comparison group, whereas the Magic Carpet test span did not significantly differ between the groups. CBT span, but not the Magic Carpet span, was related to gestational age at birth and to basic visual function. Both the CBT span and the Magic Carpet test were related to overall right-hemispheric impairment. In addition, CBT correlated with right periventricular impairment. In CP, navigation is differently impaired than visual spatial memory, and less tightly related to preterm birth, basic visual function, and deep white matter injury. The exploration of navigational space could prove useful in enhancing spatial representation and reference-frame manipulation in CP.

Is one motor cortex enough for two hands?

We report on a patient with mirror movements sustained by a mono-hemispheric fast control of bilateral hand muscles and normal hand function. Transcranial magnetic stimulation of the right motor cortex evoked contractions of muscles in both hands while no responses were observed from the left hemisphere. Somatosensory-evoked potentials, functional magnetic resonance, and diffusion tractography showed evidence of sensorimotor dissociation and asymmetry of corticospinal projections, suggestive of reorganization after early unilateral left brain lesion. This is the first evidence that, in certain rare conditions, good hand function is possible with ipsilateral corticospinal reorganization, supporting the role of unexplored mechanisms of motor recovery.

Brain representation of action observation in human infants.

Imitative learning has long been established as extremely important for early development. However, neural mechanisms involved in early imitative behaviours are still areas of active research. Neurophysiological and brain-imaging studies have been recently performed that provide initial evidence of brain activation associated with action observation in the first months of life. In this review we examine all studies exploring the effects of action observation on brain function assessed by means of non-invasive brain-mapping techniques. Seventeen papers were selected as a result of our literature search. The strongest evidence for a neural signature of action observation comes from studies exploring the desynchronization of the µ-rhythm, which was reported for both occluded and visible goal-directed grasp, and was correlated with the totality of the infant's own action experience. The effects of action observation were reported on event-related potentials (ERPs) or near infrared spectroscopy. Taken together, these studies suggest that, in early infancy, a direct visual-motor matching process is already detectable as early as 6 months, suggesting a matching between action perception and execution already in infancy. If confirmed by future studies, these findings will shed light on the mechanisms of early motor development and imitation, and will be key to informing novel rehabilitation strategies in infants with congenital brain damage.