Course:KIN366/ConceptLibrary/Central Pattern Generators

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Movement Experiences for Children
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KIN 366
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Instructor: Dr. Shannon S.D. Bredin
Email: shannon.bredin@ubc.ca
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A central pattern generator (CPG) is an ensemble of neurons which creates motor programs for stereotyped actions (Schmidt & Lee, 2011) (Balaban et al., 2015). Here, a motor program is a command, including temporal and spatial directions, sent to certain muscles resulting in the production of a coordinated movement sequence (Schmidt & Lee, 2011). A motor program is used to direct an action as simple as grasping a grape or as complex as an overhand tennis serve. Likewise, different CPGs exist for different functions in various organisms. There is a CPG for swimming in a lamprey, for grooming in a mouse, and for bipedal locomotion in a human (Schmidt & Lee, 2011); the locomotive CPG will be the only type discussed further.
While cats, other animals, and insects were used in early CPG research, recent studies have utilized human infants for more applicable results. These results can aid in understanding walking mastery in children and walking relearning for people with spinal cord injury (SCI). Furthermore, better understanding of CPGs in infants provides the evidence upon which to build therapeutic treadmill programs to aid walking acquisition for children with developmental disabilities or delays.

Localization and Structure:

In rodents, the CPG for locomotion spans multiple segments of the thoracic and lumbar spinal cord. Findings are similar for the localization of CPGs in cats, turtles, chicks, and lampreys (Kiehn & Butt, 2003). Thus far, because invasive testing is not ethical, it can only be hypothesized that CPGs in humans are distributed similarly.
While the exact structure of the CPG is not known it has often been theorized. The popular half-centre model proposed that interneurons within the spinal cord would alternatively stimulate the motor neurons connected to the flexors and extensors of each leg yielding the basic locomotive movement pattern (Schmidt & Lee, 2011). Activation of flexors or extensors predominates at any one time in each leg, with the opposite activation in the other leg. Thus the flexors of one leg are activated, bringing the leg into swing phase, while the extensors of the other leg are activated, keeping that leg in stance phase, and then they alternate.
One suggested simplified schematic of the CPG is comprised of four interneurons, two motor neurons (one to each of the flexors and extensors), and some input stimulus. The four interneurons are connected cyclically, so that neuron one synapses with two, two with three, three with four, and four back to one. Consequently, if any one neuron is stimulated the signal would theoretically continue cycling indefinitely (Schmidt & Lee, 2011). The initiating stimulus could be some sort of external input, descending control from the brain, or sensory input from the limbs. While neuron one synapses with neuron two it also synapses with a motor neuron leading to the extensor muscles. Similarly, neuron three synapses with both neuron four and a motor neuron to the flexor muscles (Schmidt & Lee, 2011). As such, the electrical signal travelling continually along the circle of interneurons will now also stimulate the flexors and then extensors via their motor neurons. While this model is likely far simplified from the actual circuitry of the CPG, it allows us to picture how such oscillatory behaviours might be controlled by the spinal cord (Schmidt & Lee, 2011).

Early Studies:

The first indications of a CPG were in studies involving cats with spinal preparations (Brown, 1911). In such preparations, researchers would cut the spinal cord below the brain so that the brain would not receive sensory feedback from the body, and so that muscles could not receive descending commands from the brain. While the cat was effectively paralyzed and could not generate volitional movements, when the researchers applied brief electrical stimulation to the spinal cord below the cut, the efferent (motor) fibers from the spinal cord displayed alternating activity (Brown, 1911). Nearly 60 years later, cats with similar spinal preparations were tested while supported on treadmills. With electrical stimulation to the spinal cord they exhibited stepping resembling that of a normal cat. Further, as the treadmill sped up the cat walked faster, and then transitioned to trotting or galloping. Researchers concluded that stepping had to be initiated by some higher centre (here, the electrical stimulus acted in place of the brain’s signal) but could then continue without further input (Shik, Orlovskii, & Severin, 1968). In further studies, the same protocol was followed except for the electrical stimulation. Instead, the treadmill was turned on so that the cat’s legs were allowed to trail behind it briefly, after which, the cat would suddenly begin stepping (Shik & Orlovski, 1976). These results showed that the sensory feedback from the legs and feet being dragged were also sufficient to initiate stepping by the CPG.

Recent Studies:

Newer research has explored CPGs with a novel set of subjects, human infants. Of course, no spinal preparations or exploratory surgeries are made. Such extreme invasive measures are not needed due to the immaturity of the cortex and descending motor tracts at birth. Axons of the corticospinal tract have diameters ten times smaller and conduct ten times slower than those in adults (Eyre, Miller, Clowry, Conway, & Watts, 2000). Furthermore, full myelination of axons is only reached by two years of age (Yakovlev & Lecours, 1967). Conversely, select neural circuity is established much earlier on, as demonstrated by fetal stepping in the womb (De Vries, Visser, & Prechtl, 1984). As such, it is generally accepted that stepping behaviours exhibited by infants below one year of age are largely free from descending brain inputs, and they are therefore ideal subjects to demonstrate the workings of human CPGs (Yang et al., 2004).
While testing on other animals has been vitally important, the ability to test intact human CPGs is necessary to account for general evolutionary changes to the CPG and those that may have accompanied bipedalism in humans (Yang et al., 2004). Testing on infants continues to reveal the incredible adaptability and sophistication of movements possible in children due to the CPG, despite their inability to walk on their own (Yang et al., 2004). These results are discussed in greater detail below. Such findings further emphasize the importance of overcoming rate limiters such as strength and balance so that infants can utilize the CPG to master walking. Indeed, infant CPG research has immense implications for infant walking acquisition in typically and non-typically developing children, and for retraining walking in those with incomplete spinal cord injuries (Yang et al., 2004). Testing people with incomplete SCIs is possible, however it is less ideal as adaptive changes may have occurred in the body after the SCI (Dimitrijevic, Gerasimenko, & Pinter, 1998).

Independent yet Integrated CPGs:

Research using a two-belt treadmill indicates that humans have one CPG for each leg, and those CPGs are able to operate independently while still communicating with each other (Yang et al., 2004). In this study, the treadmill belts could operate at different speeds and even in different directions, so that the supported infant had to adapt to and accommodate the discrepancies between legs. In normal stepping, a 1:1 ratio is followed, where both legs are stepping at the same rate so that one step of the right leg is taken for every one of the left. When the speed of one treadmill belt was significantly faster than the other, infants would compensate by taking two or three steps with the "fast foot" for every one step with the "slow foot." Impressively, some infants were even able to accommodate for a ten-fold difference in belt speed. This shows that each CPG worked independently and utilized the sensory input from its leg to devise the appropriate stepping speed. Still, there had to be some interaction between the CPGs to ensure stepping of each foot occurred at an appropriate time so that the subject would not fall over. In addition, with a speed discrepancy between the belts the infants would modify the duration of their step cycle so that it was intermediate between what they would have used if both belts were running at the fast speed or both at the slow speed. Once more, this demonstrates the ability of the CPGs to integrate information from each leg and work cooperatively, all without descending control from the brain.

Modulated Responses:

In both normal and spinalized cats the stumble corrective reflex response has been displayed (Forssberg, Grillner, & Rossignol, 1975). This occurs when some stimulus is applied to the dorsum of the foot at various stages in stepping. If applied during swing phase the cat will increase flexion, as if to clear some object that is in the way of its foot. Alternately, if applied during the stance phase the cat will show little change in stepping and perhaps even increased activation of the extensor muscles of the disturbed leg. A recent study on infants has clearly showed the same phase-dependent reflexive response (Lam, Wolstenholme, van der Linden, Pang, Yang, 2003). A baton was used to press upon the dorsum of the infant’s foot while exhibiting treadmill-induced walking. None of the children tested were able to walk independently. During swing phase, in response to the baton disturbance, the infants displayed increased flexion at the knee and hip, as well as increased height of toe trajectory. Additionally, the duration of the swing phase was lengthened. Disturbances during stance phase yielded negligible changes. Similarly, disturbances applied to the medial or lateral aspects of the foot during swing phase of forward walking had no effect because they would not have hindered walking. However, disturbances to the side of the foot during sideways stepping did elicit increased flexion. This indicates that while walking is not made up of reflexes, it is certainly modulated by them. This adds a level of sophistication to the CPG output, where without the brain’s influence, an infant can automatically correct for a disturbance to gait, but only when it is applicable to the task of walking. Clearly, this exhibits an incredible complexity of movement enabled through the CPG which is limited by the infant's immature corticospinal tract.

Application – Improving Walking Acquisition in Children with Down Syndrome

On average, children with Down syndrome (DS) learn to walk about one year later than their typically developing counterparts due to the delayed development of their nervous system (Ulrich, Ulrich, Angulo-Kinzler, & Yun, 2001). While infants with DS experience general motor delays, those delays associated with locomotion can be especially damaging due to the associated cognitive delays. Without the ability to walk, these children have limited interaction with their peers and with their environment. Utilizing the understanding of CPGs however, researchers have tested the effects of in-home therapeutic treadmill programs. Although these infants cannot walk on their own, they are able to activate the circuitry of their CPGs through the treadmill to practice walking. Such interventions are based on the assumption that increasing applicable motor experiences will help with movement mastery (Ulrich et al., 2001).
The families are supplied with a child-sized treadmill and taught how to support their child over it. The intervention was to include eight minutes on the treadmill for five days each week. The researchers found that children in the treadmill condition learned to walk with help and walk independently earlier (73.8 and 101 days, respectively) than those in the control condition (Ulrich et al., 2001). In addition, later studies discovered that children following a more intensive and personalized treadmill program acquired walking more quickly than those following a general and less intensive program (Ulrich, Lloyd, Tieman, Looper, & Angulo-Barroso, 2008). While the low intensity intervention remained constant the high intensity one included the addition of ankle weights, increases in belt speed, and increased daily duration over the course of the study. Without doubt, these treadmill programs are not a perfect solution; they cannot accelerate walking acquisition in children with DS to follow the timeline of a typically developing child. However, they have proven to be valuable therapeutic interventions to include in addition to regular physical therapy for young children with DS (Ulrich et al., 2008). In this way, our understanding of CPGs isimproving live for children with DS and for their families.  

References:

  • Balaban, P.M., Vorontsov, D.D., D’yakonova, V.E., D’yakonova, T.L., Zakharov, I.S., Korshunova, T.A., Orlov, O.Y., Pavlova, G.A., Panchin, Y.V., Sakharov, D.A. & Falikman, M. V. (2015). Central pattern generators. Neuroscience and Behavioral Physiology, 45 (1), 42-57, doi:10.1007/s11055-014-0039-7
  • Brown, T.G. (1911). The intrinsic factors in the act of progression in the mammal. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 84, 308-319, doi: 10.1098rspb.1911.0077
  • De Vries, J.I.P, Visser, G.H.A., & Prechtl, H.F.R. (1984). Fetal motility in the first half of pregnancy. In H.F.R. Prechtl (Ed.), Continuity of neural functions from prenatal to postnatal life (pp.46-64), Oxford: International Medical Publications.
  • Dimitrijevic, M.R., Gerasimenko, Y., & Pinter, M.M. (1998). Evidence for a spinal central pattern generator in humans. Annals of the New York Academy of Sciences, 860, 360-376, doi: 10.1111/j.1749-6632.1998.tb09062.x
  • Eyre, J. A., Miller, S., Clowry , G. J., Conway , E. A., & Watts, C. (2000). Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres. Brain, 123, 51-64, doi:http://dx.doi.org/10.1093/brain/123.1.51
  • Forssberg H., Grillner S., & Rossignol S. (1975). Phase dependent reflex reversal during walking in chronic spinal cats. Brain Research, 85,103–107.
  • Kiehn, O., & Butt, S.J.B. (2003). Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord. Progress in Neurobiology, 70 (4), 347-361, doi:10.1016/S0301-0082(03)00091-1
  • Lam, T., Wolstenholme, C., van der Linden, M., Pang, M.Y.C., Yang, J.F. (2003). Stumbling corrective responses during treadmill-elicited stepping in human infants. Journal of Physiology, 553(1), 319–331, doi: 10.1113/jphysiol.2003.043984
  • Schmidt R.A., & Lee, T.D. (2011). Central contributions to motor control. In M. Schrag, M.J. Zavala, A. Pomata, S. Calderwood, & J. Sexton (Eds.) Motor control and learning: a behavioral emphasis (pp. 177-222). Champaign, IL: Human Kinetics.
  • Shik, M.L., Orlovskii, G.N., & Severin, F.V. (1968). Locomotion of the mesencephalic cat elicited by stimulation of the pyramids. Biofizika, 13, 143-152.
  • Ulrich, D.A., Lloyd, M.C., Tieman, C.W., Looper, J.E., & Angulo-Barroso, R.M. (2008). Effects of intensity of treadmill training on developmental outcomes and stepping in infants with Down Syndrome: a randomized trial. Physical Therapy, 88 (1), 114-122, doi: 10.2522/ptj.20070139
  • Ulrich, D.A., Ulrich, B.D., Angulo-Kinzler, R.M., & Yun J. (2001). Treadmill training of infants with Down syndrome: evidence-based developmental outcomes. Pediatrics, 108 (5), 84-90, doi:10.1542/peds.108.5.e84
  • Yakovlev, P.I., & Lecours, A.R. (1967). The myelogenetic cycles of regional maturation of the brain. In A. Minkowski (Ed.), Regional development of the brain in early life (pp. 3-70). Oxford: Blackwell Scientific Publications.
  • Yang, J.F., Lam, T., Pang, M.Y.C., Lamont, E., Musselman, K., & Seinen, E. (2004). Infant stepping: a window to the behaviour of the human pattern generator for walking. Canadian Journal of Physiology and Pharmacology, 82 (8-9), 662-674, doi:10.1139/Y04-070
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