Periodic Reporting for period 4 - Learn2Walk (Brain meets spine: the neural origin of toddler’s first steps) Reporting period: 2021-08-01 to 2022-07-31 Summary of the context and overall objectives of the project Immediately after born neonates can instinctively walk. When supported by a parent or a doctor for 70-80% of their weight and their feet touch the surface, they are able to perform stepping patterns that is a primitive reflex hardwired in our neural circuitry, that is known as ‘stepping reflex’. These early stepping movements can also be observed in anencephalic infants and even before born in in human foetuses that suggests a predominant role from the spinal cord and brainstem as the neocortex and the motor descending from the cortex to the spinal cord are still immature at the birth. Typically developing (TD) children start to walk independently at the age of around 12 months, and this moment triggers fundamental developmental changes. In fact, failing to reach independent walking by an age of 18-20 months may indicate developmental delay. Cerebral palsy (CP) is one of the most common developmental motor disorders, it describes a group of permanent disorders of the development of posture and movement that are caused by non-progressive lesions in an immature brain. Most children with CP received diagnosis during the first two years of life, but when the child’s symptoms are mild, it might be initially overlooked, making a reliable diagnosis before the age of 4 or 5 is challenge. Although about 2/3 of children with CP manage to walk before the age of 5, they often exhibit hardly functional and unstable locomotion. Our project aimed to characterize the emergence of independent walking in TD children and children with CP. It sought to understand the interplay between brain and muscular activity before – during - and after- this crucial developmental phase in healthy children and in children with a visible lesion precisely in the brain (children with high risk of developing CP); it aimed to identify differences in the biomechanical aspect, in the muscular and brain activation underlying the development of walking; it sought to understand the effect of the current rehabilitation techniques performed in children with cerebral palsy in their neuromotor abilities. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far We have developed and optimized an innovative recording platform that allowed recording of brain activity in conjunction with multi-muscles activity and whole-body kinematics for neonate and toddlers during over-ground and treadmill walking. This setting is allowing us to unveil the biomechanical and neural mechanisms underlying the emergence of walking, and to study the changes in the functional architecture and dynamics of the cortical activity. We studied changes in gait movement and neuromuscular control in both TD children and children with high risk of developing CP. We also implemented an innovative methodological approach to quantify gait-related cortico-spinal entrainment in toddlers that learn to walk. Until recently, only a handful of studies addressed neural correlates of gait in humans and even more in young children, due to the challenge of recording the brain activity while walking. During this project we investigated in particular the ability of the primary motor cortex to entrain the output of group of muscles (also known as muscle synergies or locomotor primitives) in walking children. We showed that in the locomotor muscle synergies are represented in the sensorimotor cortex, and the two (out of the four) muscle synergies that are known to develop around the onset of independent walking displayed significant cortical representation compared to the other two synergies.We have developed a new approach to study the neural interactions on multiple time scales using network structure that was used to study the sensorimotor integration and its effect on motor control in toddlers at the onset of independent walking and after months of independent walking experience. Moreover, we are employing sophisticated multivariate statistics (i.e. principal component analysis and hierarchical clustering) on a large number of gait variable to identify key parameter that are responsible for the modification of the gait pattern during the development od walking. These results also informed about the degree of maturity of the locomotor patterns.These combined methodologies and studies are thus yielding scientific results that are increasing our understanding of the mechanisms underlying the emergence of walking in children. Many results have been disseminated via open access publications and national/international conferences. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Overall, this work increased our understanding of the interplay between biomechanical aspects and muscular and brain activity during the emergence of walking in children. The unique data set collected during this project consisted of longitudinal and cross-sectional data, from neonates’ stepping until toddlers’ independent walking, and it allows to address fundamental questions on the emergence of walking from a novel perspective, in typically developing children and children with motor impairment. We developed a new methodological approach to study the cortico-spinal coherence. Toddler's first independent steps
