A neuro-biomechanical model that highlights the ability of spinal sensorimotor circuits to generate oscillatory locomotor outputs

The goal of this project is to uncover the functional role of proprioceptive sensorimotor circuits in motor control, and to understand how their recruitment through electrical stimulation can elicit treadmill locomotion in the absence of brain inputs. This understanding is pivotal for the translation of experimental spinal cord stimulation therapies into a viable clinical application.

To this aim, we developed a closed loop neuromusculoskeletal model that encompass a spiking neural network of the muscle spindle pathway of two antagonist muscles, a musculoskeletal model of the mouse hindlimb, and a model of epidural electrical stimulation (Figure 1). The network includes alpha motoneurons, Ia inhibitory interneurons, group II excitatory interneurons, and group Ia and group II afferent fibers. The number of cells, the connectivity, and the firing behavior of alpha motor neurons was tuned according to experimental values found in literature. The effect of epidural electrical stimulation was integrated in the neuronal network by modelling every stimulation pulse as a supra threshold synaptic input in all the cells recruited by the stimulation. An experimentally validated FEM model of the lumbar rat spinal cord was used to compute the percentage of fibers recruited by the stimulation.

Closed loop simulations were performed by using the firing rates of the motoneurons populations as a signal to control the muscles activity of the musculoskeletal model, while using the muscles length information coming from the musculoskeletal model to estimate the firing rates of the neural network afferent fibers. In particular, the firing rates of Ia and II afferent fibers were estimated using an experimentally derived muscles spindle model.

The preliminary results show that muscle spindle feedback circuits alone can produce alternated movements typical of locomotion, when biomechanics and gravity are considered.

Current work is being performed in order to expand the modeled muscle spindle circuitry to control all the main hindlimb muscles together. To this purpose, the developed network will be used as a template for every couple of antagonist muscles and heteronymous connections across the different joints will be implemented. With this complete model of the hindlimb muscle spindle circuitry we will be able to assess whether this single sensorimotor pathway is sufficient to produce treadmill locomotion in combination with EES, or whether other spinal neural networks are necessarily involved.

HBP_Blog1

Figure 1 : Closed loop simulation framework of Spinal Cord model and rodent hind limb to study epidural electrical stimulation

  • Emanuele Formento (PhD, TNE & G-Lab, EPFL)
  • Shravan Tata Ramalingasetty (PhD, BioRob, EPFL)
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