The spinal cord nerve circuits that affect arm function are closely networked with the circuits that affect stepping patterns in the legs. Work published this week by Prithvi Shah and a group from the Reggie Edgerton
lab at UCLA (a member lab of the Reeve International Research Consortium on Spinal Cord Injury
) shows that upper arm training enhances locomotor recovery of the legs.
Photo: Pri Shah, right, with co-author Guillermo Garcia-Alias.
The paper, appearing in the journal Brain, is titled “Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.
It’s not news that there is significant neural coupling between arms and legs. Indeed, the current paper cites work from the Edgerton lab several years ago wherein arm training alone
was shown to drive stepping patterns in decerebrate (no brain connnection) cats. There is a fair amount of other evidence, also cited by Shah et al
, that links nerve networks between arms and legs.
The working theory behind Edgerton’s work is that the spinal cord is densely woven with segmental nerve circuits that respond to information coming from the body -- but not necessarily from the brain. These nerve networks are able to process sensory information (such as the loading of weight or the placement of feet on a moving treadmill) and can activate what scientists call a central pattern generator. This is the basis for Locomotor Training and for human experiments
with epidural stimulation and training that have resulted in some recovery of stepping function and significant gains in autonomic function (temperature control, bowel, bladder, and sexual function).
Shah and her team ask this question: Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs?
We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal [tracking both above and below the lesion] spinal interneuronal networks.
The experiment used spinal cord injured rats (T-10 hemisection, or partially paralyzed). The test animals were fitted with sensors for measuring electrophysiological information from both forelimbs and hindlimbs. Each animal underwent 17 sessions of treadmill step training for both upper and lower extremities. A subset had lower limb training alone. In addition to electrical tracking the animals were videotaped to observe and record very fine 3-D kinematic detail in their limb coordination and locomotor skills.
To provide insight into the nerve networks themselves, the scientists injected a tracer dye into the spinal cords at the time of surgery. Later, the dye treatment allowed them to examine the spinal cords to see evidence that the nerve networks had indeed been plastic; in other words, they had expanded. From the paper:
To our knowledge, no studies have determined the impact of functionally engaging the forelimbs to improve coordinated quadrupedal locomotion or have emphasized the effects of engaging the propriospinal [the interneural network] pathways connecting cervico-thoraco-lumbar networks to promote recovery after a spinal cord injury.
And the results?
We hypothesized that actively involving the forelimbs would facilitate the recovery of locomotor function after a spinal cord injury. We demonstrate three novel findings: (i) actively engaging both the forelimbs and hindlimbs in a training paradigm (quadrupedal step-training) results in superior locomotor quality and coordination than training only the hindlimbs (bipedal step-training) or not training (non-trained); (ii) quadrupedal step-training is associated with greater excitability of motor neurons as is reflected in the lower levels of excitation thresholds of epidurally evoked potentials in the hindlimb muscles in both the lesioned and nonlesioned sides; and (iii) quadrupedal step-trained rats exhibit a significantly greater level of rostrocaudal thoracic interneuron connectivity as the they showed the highest number of labeled propriospinal neurons above and below the hemisection site bilaterally.
To recap, the animals that trained both upper and lower limbs were more coordinated and more functional that those with lower limbs training only. This was clearly shown in behavioral tests. The scientists also looked at the electrical properties of the nerve circuits; they are made stronger by adding upper limb training, leading Shah to speculate that step-training increases the recruitment and excitability of hindlimb motor nerves. And the team also looked at post-mortem evidence of nerve circuitry. The training effect clearly enhanced the ability of spinal circuits to expand.
What’s significant about this?
For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage.