Developmental plasticity | EPFL Graph Search

Developmental plasticity is a general term referring to changes in neural connections during development as a result of environmental interactions as well as neural changes induced by learning. Much like neuroplasticity, or brain plasticity, developmental plasticity is specific to the change in neurons and synaptic connections as a consequence of developmental processes. A child creates most of these connections from birth to early childhood. There are three primary methods by which this may occur as the brain develops, but critical periods determine when lasting changes may form. Developmental plasticity may also be used in place of the term phenotypic plasticity when an organism in an embryonic or larval stage can alter its phenotype based on environmental factors. However, a main difference between the two is that phenotypic plasticity experienced during adulthood can be reversible, whereas traits that are considered developmentally plastic set foundations during early development t

Corticolumbar dynamics during recovery after spinal cord injury

Selin Anil

In humans, a severe spinal cord contusion interrupts the vast majority of supraspinal projections to the spinal cord below the lesion. Permanent paralysis results from the chronic failure of these spared projections to engage lumbar circuits producing leg movement. We modeled these injuries in rodents, and showed the immediate access of cortical circuits onto the electrochemically-enabled lumbar spinal cord. Neuroprosthetic rehabilitation leveraged spared motor circuits elements, ultimately leading to the establishment of a cortico-reticulo-spinal relay that mediated the recovery of voluntary control over the legs. Cortical fibers underwent a drastic anatomical remodeling, contacting glutamatergic reticulospinal neurons in the brainstem which, despite lesion variability, consistently retained synaptic connections onto lumbar circuits. This circuit-level reorganization mediated a cortex-dependent recovery of natural locomotor behaviors. In the aim of refining our understanding of the cortical contribution to the restoration of leg motor control with neuroprosthetic rehabilitation, we established a methodology to translate to rats a technique of endoscopic calcium imaging in freely-moving animals. We increased the stability of the implant, reaching unprecedented chronic degrees of longevity. Using this newly implemented technology, we tracked the activity of single corticolumbar cells during natural walking in intact rats, showing a strong representation of motor behavioral features in the population. We additionally highlighted the stability of locomotion-related classifications of individual neurons, suggesting a segregation of movement-related representations. The contusion was accompanied by important anatomical changes of corticolumbar cell bodies, preventing the longitudinal identification of single neurons across injury. However, population-level analyses highlighted a maintained strong representation of locomotion at late stages after injury and training. We did not find any dynamic change in corticolumbar population activity correlating with the recovery of voluntary leg motor control, which reflected in a stability of the fractions of movement-related neurons. These early results start shedding light on possible mechanisms of functional plasticity accompanying recovery after spinal cord injury, as a peculiar form of motor learning. Concurrently to the functional reorganization of corticolumbar neurons, we investigated the anatomical plasticity of this specific population with contusion and training. Neuroprosthetic rehabilitation led to a strengthening of collateral connections onto the thoracic spinal segments above the lesion. However, we found no effect of training on the anatomical remodeling throughout the brain and brainstem. Notably, the absence of sprouting of corticolumbar collaterals in the brainstem reticular formation leads us to question the identity of the cortical population involved in the formation of the cortico-reticulo-spinal relay.

EPFL2020

Central and peripheral mechanisms: a multimodal approach to understanding and restoring human motor control

Nawal Noëlle Kinany

All human actions involve motor control. Even the simplest movement requires the coordinated recruitment of many muscles, orchestrated by neuronal circuits in the brain and the spinal cord. As a consequence, lesions affecting the central nervous system, such as stroke, can lead to a wide range of motor impairments. While a certain degree of recovery can often be achieved by harnessing the plasticity of the motor hierarchy, patients typically struggle to regain full motor control. In this context, technology-assisted interventions offer the prospect of intense, controllable and quantifiable motor training. Yet, clinical outcomes remain comparable to conventional approaches, suggesting the need for a paradigm shift towards customized knowledge-driven treatments to fully exploit their potential. In this thesis, we argue that a detailed understanding of healthy and impaired motor pathways can foster the development of therapies optimally engaging plasticity. To this end, we develop and apply multimodal methodologies to investigate the central and peripheral mechanisms underlying motor control and recovery. In the first part of this work, we concentrate on the transition from one-suits-all approaches to patient-tailored protocols, in the context of robot-assisted rehabilitation. We start addressing this question from a technical viewpoint and propose methods to assess individual dynamics of recovery in stroke patients. First, we demonstrate the applicability of a model-based approach to continuously personalize training based on kinematic motor improvement. Then, we show how complementary knowledge can be gleaned from kinematics, muscular and neural signals, and we introduce a versatile framework to distill this multimodal information into a set of clinically relevant variables. These results highlight the pivotal importance of multimodality, stressing the need for a comprehensive view of the human motor hierarchy. To this end, the second part of this work focuses on the spinal cord, whose functional properties remain largely unexplored in humans. As this gap of knowledge primarily pertains to the dearth of non-invasive methods to assess its function in vivo, we first propose a pipeline for spinal cord functional magnetic resonance imaging (fMRI) and demonstrate its ability to capture cervical activation patterns during upper limb movements. We then present a dynamic functional connectivity framework to dissect spinal spontaneous fluctuations into fine-grained components mirroring neuroanatomical and physiological principles. Next, we extend the use of this approach to fMRI data acquired in the entire neural axis during motor sequence learning, hence shedding light on specific cortical, subcortical and spinal correlates of skill acquisition and consolidation. Finally, we glimpse into the implementation of these methodologies in the scope of translational applications, providing evidence of their potential to explore spinal plasticity following stroke. These findings are a valuable contribution towards an extensive characterization of human motor control. This system-level view deepens our understanding of motor pathways, fully acknowledging the active and plastic nature of the spinal cord and emphasizing its key role in sensorimotor functions. We envision that the synergy between technology and knowledge will open promising avenues for strategies leveraging each patientâs residual function to optimize clinical outcome.

EPFL2020

Central and peripheral mechanisms: a multimodal approach to understanding and restoring human motor control

Nawal Noëlle Kinany

EPFL2020

Corticolumbar dynamics during recovery after spinal cord injury

Selin Anil

EPFL2020