Irina A. Solopova

Human motor functions are formed as a result of a dynamic interaction between the developing nervous system and the musculoskeletal system, the transition from spontaneous fetal movements to the control of upright posture and the development of locomotion. Careful analysis of these motor patterns in early ontogenesis can provide insight into the functional integrity of spinal and supraspinal networks and identify early developmental deviations in high-risk groups, such as preterm infants. The method of quantitative muscle activity analysis, based on the recording of electromyographic and kinematic parameters during spontaneous and passive limb movements, allows for an objective assessment of motor variability, inter-limb coordination, and neuromuscular activation. Using this method, we previously obtained quantitative characteristics and features of muscle reaction formation in term and preterm infants. In the present study, the capabilities of this method are illustrated through an individual clinical observation of a very preterm infant. Despite unfavorable initial clinical prerequisites – extremely low birth weight, pronounced morpho-functional immaturity, signs of periventricular leukomalacia on cranial ultrasound, and very slow motor skill acquisition significantly lagging behind corrected age norms–the application of an objective neurophysiological approach allowed for the prediction and tracking of positive dynamics and subsequent favorable development of motor functions. Thus, quantitative neurophysiological analysis of muscle activity enables an objective assessment of sensorimotor circuit maturation and holds clinical and prognostic significance.

Given the cervical spinal cord’s role in locomotor and rhythmic upper limb tasks, its neuromodulation has emerged as an important area of study for understanding human spinal rhythmogenesis. We previously demonstrated that, under unloading conditions, arm muscle vibrostimulation can elicit non-voluntary upper limb oscillations. In this study, we investigated the effects of transcranial magnetic stimulation (TMS) of the motor cortex during both voluntary and non-voluntary (vibration-induced) rhythmic arm movements. We analyzed motor-evoked potentials, mean arm muscle activity, and kinematic parameters of arm movements, including cycle duration and shoulder and elbow joint angular oscillations. Motor-evoked potentials in proximal arm muscles were significantly modulated during both movement types. Notably, low-frequency TMS markedly enhanced non-voluntary arm oscillations, whereas its effect on voluntary movements was statistically non-significant. This differential response is likely due to the absence of characteristic supraspinal influences in sensory-induced spinal activation during non-voluntary movements. These findings align with previous evidence showing that supraspinal pathways facilitate rhythmogenesis in the lower limbs, and they now extend this concept to the upper limbs. Overall, our results suggest that therapies aimed at modulating cervical central pattern generators may benefit from the active engagement of supraspinal motor circuits.

Given the cervical spinal cord’s role in locomotor and rhythmic upper limb tasks, its neuromodulation has emerged as an important area of study for understanding hu-man spinal rhythmogenesis. We previously demonstrated that, under unloading conditions, arm muscle vibrostimulation can elicit non-voluntary upper limb oscillations. In this study, we investigated the effects of transcranial magnetic stimulation (TMS) of the motor cortex during both voluntary and non-voluntary (vibration-induced) rhythmic arm movements. Motor-evoked potentials in proximal arm muscles were significantly modulated during both movement types. Notably, low-frequency TMS markedly enhanced non-voluntary arm oscillations, whereas its effect on voluntary movements was minimal. This differential response is likely due to the absence of characteristic supraspinal influences in sensory-induced spinal activation during non-voluntary movements. These findings align with previous evidence showing that supraspinal pathways facilitate rhythmogenesis in the lower limbs, and they now extend this concept to the upper limbs. Overall, our results suggest that therapies aimed at modulating central pattern generators in the cervical spinal cord may benefit from the active engagement of supraspinal motor circuits.

Manifestation of muscle reactions at an early developmental stage may reflect the processes underlying the generation of appropriate muscle tone, which is also an integral part of all movements. In preterm infants, some aspects of muscular development may occur differently than in infants born at term. Here we evaluated early manifestations of muscle tone by measuring muscle responses to passive stretching (StR) and shortening (ShR) in both upper and lower limbs in preterm infants (at the corrected age from 0 weeks to 12 months), and compared them to those reported in our previous study on full-term infants. In a subgroup of participants, we also assessed spontaneous muscle activity during episodes of relatively large limb movements. The results showed very frequent StR and ShR, and also responses in muscles not being primarily stretched/shortened, in both preterm and full-term infants. A reduction of sensorimotor responses to muscle lengthening and shortening with age suggests a reduction in excitability and/or the acquisition of functionally appropriate muscle tone during the first year of life. The alterations of responses during passive and active movements in preterm infants were primarily seen in the early months, perhaps reflecting temporal changes in the excitability of the sensorimotor networks.

The state and excitability of pattern generators are attracting the increasing interest of neurophysiologists and clinicians for understanding the mechanisms of the rhythmogenesis and neuromodulation of the human spinal cord. It has been previously shown that tonic sensory stimulation can elicit non-voluntary stepping-like movements in non-injured subjects when their limbs were placed in a gravity-neutral unloading apparatus. However, large individual differences in responsiveness to such stimuli were observed, so that the effects of sensory neuromodulation manifest only in some of the subjects. Given that spinal reflexes are an integral part of the neuronal circuitry, here we investigated the extent to which spinal pattern generation excitability in response to the vibrostimulation of muscle proprioceptors can be related to the H-reflex magnitude, in both the lower and upper limbs. For the H-reflex measurements, three conditions were used: stationary limbs, voluntary limb movement and passive limb movement. The results showed that the H-reflex was considerably higher in the group of participants who demonstrated non-voluntary rhythmic responses than it was in the participants who did not demonstrate them. Our findings are consistent with the idea that spinal reflex measurements play important roles in assessing the rhythmogenesis of the spinal cord.

Motor activity of infants becomes detectable as early as the first months (9–10 weeks) of fetal development. These movements constantly change during maturation of the fetus, are preserved after birth, and are called general movements. The complexity and variability of movements is a criterion for the normal motor development of infants in the postnatal period. Disturbances in maturation of the nervous system are reflected in abnormal patterns of general movements, and the patterns thus make it possible to diagnose perinatal brain lesions early. This is especially important in the case of preterm infants, who are at higher risk of developing neurological and motor disorders. This review describes the main types of general movements characteristic of normal motor development, the atypical motor patterns that have a predictive value for early prediction of cerebral palsy, and the putative neural substrates that determine the development of normal and abnormal general movements. Various methods are available for assessing general movements, including both qualitative techniques, which are based on visual assessment of motor patterns, and quantitative methods, which employ technologies of automated general movement recognition and analysis.

Mature locomotion involves modular spinal drives generating a set of fundamental patterns of motoneuron activation, each timed at a specific phase of locomotor cycles and associated with a stable muscle synergy. How locomotor modules develop and to what extent they depend on prior experience or intrinsic programs remains unclear. To address these issues, we herein leverage the presence at birth of two types of locomotor-like movements, spontaneous kicking and weight-bearing stepping. The former is expressed thousands of times in utero and postnatally, whereas the latter is elicited de novo by placing the newborn on the ground for the first time. We found that the neuromuscular modules of stepping and kicking differ substantially. Neonates kicked with an adult-like number of temporal activation patterns, which lacked a stable association with systematic muscle synergies across movements. However, on the ground neonates stepped with fewer temporal patterns but all structured in stable synergies. Since kicking and ground-stepping coexist at birth, switching between the two behaviors may depend on a dynamic reconfiguration of the underlying neural circuits as a function of sensory feedback from surface contact. We tracked the development of ground-stepping in 4- to 48-mo-old infants and found that, after the age of 6 mo, the number of temporal patterns increased progressively, reaching adult-like conformation only after independent walking was established. We surmise that mature locomotor modules may derive by combining the multiple patterns of repeated kicking, on the one hand, with synergies resulting from fractionation of those revealed by sporadic weight-bearing stepping, on the other hand.

Muscle tone represents one of the important concepts for characterizing changes in the state of the developing nervous system. It can be manifested in the level of activity of flexors and extensors and in muscle reactions to its passive stretching (StR) or shortening (ShR). Here we investigated such reactions in a cohort of healthy infants aged from 2 weeks to 12 months. We examined the presence and the characteristics of StR and ShR during slow passive cyclic flexion/extension movements (T~3 s) in the hip, knee, ankle, and elbow joints while awake infants were in the supine position. The results showed that most infants demonstrated prominent ShRs in response to passive joint rotations, although the StR was observed more frequently, suggesting that the ShR is an important component of adaptive motor behavior already at an early developmental stage. Interestingly, the occurrence of both StR and ShR in most muscles significantly decreased throughout the first year of life. Passive cyclic flexion/extension movements could also evoke rhythmic muscle responses in other joints or in the contralateral limb, however, such responses were predominantly observed in younger infants (<6 months). A noticeable manifestation of muscle reactions at an early developmental stage, along with spontaneous motor activity in this period of life, may reflect the processes underlying a formation of appropriate muscle tone and the self-organization of neural circuits. A substantial reduction of ipsilateral and contralateral muscle responses to passive movements with age is consistent with the idea of a functional reorganization of the motor circuitry during early development.

Locomotion of mammals, including humans, is based on the rhythmic activity of spinal cord circuitries. The functioning of these circuitries depends on multimodal afferent information and on...