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Minassian Et Al 2017

The Human Central Pattern Generator for Locomotion: Does It Exist and Contribute to Walking?

Tags: #CPG #central_pattern_generators #locomotion #gait #neuroscience #fictive_locomotion

Related: [[An optimality principle for locomotor central pattern generators - Ryu Kuo 2021]] [[Control of Animal Locomotion by Ventral Spinocerebellar Tract Neurons - Chalif Et Al 2022]]

Key Definitions

SCI: Spinal cord injury

Fictive Locomotion: Electroneurographic activity with cyclic alternation between nerves to locomotive muscles in the absence of movement

Electromyography: Measures muscle response through electrical activity following stimulation by a nerve

Key Takeaways

  1. There is an outstanding debate about whether central pattern generators (CPGs) exist in humans, and if they do how they contribute to human walking
    • CPGs were defined as the generation of rhythmic motor activity by spinal circuits after experimental severing of supraspinal control and movement related afferent feedback. There is no human injury model that replicates these conditions (and it is obviously unethical to create them).
      • CPGs are defined not as creating rhythmic movement, but as rhythmic neural activity in the absence of movement.
      • CPGs are spinal neural circuits that can utonomously generate fictive locomotion in the absence of connection to the brain/movement related feedback
    • There is (or was initially) no convincing evidence for the presence of CPGs in human-like primates
    • Humans with severe SCIs have limited recovery of gate, indicating that movement related feedback is necessary for gait in humans
  2. CPGs have been well studied in animals, including in lamprey, cats, and rats
    • Mammalian CPGs are functionally subdivided into rhythm generating circuits and pattern generating circuits
      • Rhythm generating circuits drive the CPG network and set the pace of locomotion
      • Pattern generating circuits distribute the rhythm to the motorneuron pools
        • Flexor-extensor pattern generators control intralimb coordination
        • Left-right pattern generators coordinate between limbs
    • The intensity of electrical signal applied to a decerebrated cat can change it's speed from a slow walk all the way to a gallop, showing that spinal circuits not only cause gait timing but also the pattern of limb movements (different movements differentiate walk from trot and gallop)
  3. Neurophysiological studies of humans with SCIs show that involuntary rhythmic leg movements can appear spontaneously or be generated by electrical spinal cord stimulation
    • The following features of spontaneous involuntary leg movements are taken as reflections of CPG activity in humans
      • These involuntary leg movements are smooth and wave-like in appearance, and are made with multiple joints of the leg while lying down, closely resembling stepping
      • Movements occur spontaneously in both incomplete and complete cervical SCI
      • Spontaneous leg motions more closely resemble stepping in terms of ROM than voluntary attempts at stepping from same patient (illustration)
    • Similar rhythmic leg movements were found to be generated by electrical stimulation of the spinal cord
      • Patients were supine, meaning they were in a position of least sensory feedback about limb positions and gait phase transitions
      • Electromyographic patterns resembled locomotion patterns with reciprocity between antagonists (ex. quad flexing while hamstring relaxes)
      • Conversion of a sustained electrical impulse into coordinated rhythmic motor output is taken as evidence of CPGs in human
  4. A neuropharmacological study showed that oral application of systemic neuromodulators can trigger rhythmic muscle activity and left/right alternating muscle movements in the legs while supine
    • Rhythmic neural activity responsible for locomotion relies on neurotransmitters used and released by the brain and spinal cord. Different neurotransmitters have been shown to influence CPG in different ways
    • Individuals with SCIs who retained some motor control had rehab benefits from introduction of certain neurotransmitters, but mostly from their anti-spastic effects
    • "Spinalon" drug was able to trigger electromyographical activity and involuntary movement
      • In some cases key locomotor characteristics such as rhythmicity, flexor-extensor reciprocity, and left-right alternation were shown
      • Not all cases showed all characteristics and some showed no effect
  5. Even if CPGs are found to exist in humans, there is a view that they are phylogenetic holdovers that only become active after they have been severed from supraspinal motor centers. The alternative to this is that CPGs play an active role in normal locomotion.
    • Infants exhibit a very similar supine coordinated stepping reflex to those of individuals with SCIs, called infant stepping. Based on the gradual transformation of an infant stepping reflex into actual adult locomotion, and the continued exhibition of this reflex in adults with SCI, it appears the stepping comes from CPGs that remain active into adulthood and are integrated into neural control of locomotion
    • Simulated models have shown that CPGs can be integrated into models of descending commands as part of a control system for a model of walking. However, models have also replicated the purported CPG benefit of controlling walking speed with spinal reflex pathways instead. However, CPG based models have the benefit of being feedforward, and thus robust against sensor noise [[An optimality principle for locomotor central pattern generators - Ryu Kuo 2021]]
  6. Conclusions:
    • There is still no direct evidence for fictive locomotion in humans, however there are studies that show CPG-like rhythmic muscle activation in the absence of volition and sensory feedback
    • Furthermore, these can be triggered spontaneously with electrical impulse or pharmacological application of neurotransmitters, just like fictive locomotion in animals
    • Taken together, these argue that CPGs exist in the human spinal cord
    • If CPGs are found in the spinal cord, it makes sense that our motor control system would use them in order to reduce the complexity of descending neural control
    • CPGs are a potential target of research for rehabilitation of SCI patients
      • Current attempts have not been successful, but pharmacotherapy suggests a potential inroad

Limitations

  1. There is still no direct evidence of fictive locomotion in humans equivalent to that shown in animals
  2. Evidence that humans have CPGs is insufficient to show that CPGs play an active role in human walking, and aren't just phylogenetic holdovers
  3. Simulated models have shown that spinal reflexes can provide some of the control benefits purported to come from CPGs, so CPGs may not be theoretically necessary for human locomotion