User:Gouldjr/Neural control of locomotion

The Neural Control of Locomotion refers to the manner by which the nervous system activates skeletal muscle in the appropriate sequence (timing of muscle activation) and with the appropriate magnitude (level of force output generated by the muscle) so as to produce coordinated movement of the body and limbs. This coordinated movement allows the body to move about the environment.

The nervous system is made up of the brain, spinal cord, and peripheral nerves. The brain and the spinal cord produce commands to activate skeletal muscle, but also receive sensory signals from the periphery, which provide feedback to modulate the motor command. The motor output and the sensory input both play important roles in coordinating the movement required for locomotion.

Spinal cord
In 1911, Thomas Graham Brown Thomas Graham Brown showed that the fundamental rhythmic and alternating activity needed for locomotion could be produced alone by the spinal cord. His study used a cat preparation, in which the spinal cord was transected (there was no longer input from the brain to the spinal cord) and deafferented (there was no longer input from the sensory nerves to the spinal cord) in order to show that a flexor muscle and an extensor muscle of the ankle joint (tibialis anterior and gastrocnemius muscles) contract rhythmically, as seen in naturally occurring locomotion. Graham Brown’s findings led to the idea that the spinal cord contains interconnections between neurons that allow for rhythmic, alternating outputs in the absence of alternating inputs from higher centers of the nervous system or the peripheral nervous system (sensory feedback). Graham Brown termed these networks of neurons ‘half-centers’. One half-center activates the motor neurons innervating the flexor muscle, while the other half-center activates the extensor muscle. He showed that one of the half-centers would inhibit the other, such that only one could be active at a given time.

These half-centers form what is known as a central pattern generator or CPG, which consist of neuronal circuits that are capable of automatically producing coordinated motor patterns in response to central inputs. The neurons of central pattern generators and their cellular properties (such as delayed excitation and post-inhibitory rebound have been studied extensively in the lamprey due to their relative simplicity compared with other animals.

Brain
Despite the ability of the spinal cord to generate the basic pattern of signals necessary for locomotion, supraspinal structures such as the motor cortex, brainstem, cerebellum, and other structures are important for the initiation and termination of locomotion, controlling the speed and gait pattern of locomotion, and adapting locomotor output in response to changes in the environment detected by the limbs.

Mesencephalic locomotor region
The mesencephalic locomotor region (MLR) was first discovered in cats by Shik et al. in 1966. Their classic study showed that the speed of locomotion was directly related to the intensity of electrical stimulation applied to the MLR. Low stimulus intensities resulted in walking, and subsequent increases in intensity led to trotting and then galloping, thus demonstrating the role of the MLR in controlling the speed of locomotion as well as the pattern of gait. While these findings seem to suggest that the MLR may provide tonic or continuous drive to central pattern generators via reticulospinal pathways, it was later shown that activity in reticulospinal neurons is rhythmic and is in-phase with the step cycle.

More recently, functional magnetic resonance imaging (fMRI) studies have shown increased BOLD signals in the MLR during mental imagery of walking and running in humans (Jahn et al. 2008).

Cerebellum
The role of the cerebellum in regulating the descending drive to produce a coordinated and consistent locomotor pattern is fairly well documented. Cerebellar lesions are known to produce an ataxic gait due to increased variability in speed and range of limb movements, even when walking on smooth, flat surfaces. The cerebellum is thought to receive proprioceptive information about the actual movement of the limb, and compare this to the intended movement, so as to send corrective signals to various other brainstem nuclei that influence the descending drive to the central pattern generators.

The cerebellum may also contribute to the rhythmic discharge of reticulospinal neurons. This rhythmic output was thought to have been driven by the rhythmic output of the MLR, however, surgical removal of the cerebellum results in tonic output of the reticulospinal neurons (Orlovsky 1970b).

Motor cortex
The motor cortex has been shown to be most important in ‘skilled’ locomotion, which requires the precise placement of the feet on the surface being walked on. Lesions to the motor cortex do not seem to impair walking on flat ground. However, in 1911, Trendelenburg showed that compromising the corticospinal tract by cooling the motor cortex in both cats and dogs, temporarily impaired their ability to walk on a grid that required them to place their feet in certain spots. Similarly, in 1944, Liddell and Philips demonstrated the inability of cats with corticospinal lesions (in the medullary pyramids) to walk along a narrow beam or along the rungs of a horizontal ladder, whereas near-normal walking was observed on flat ground.

Sensory input
Sensory input is also important for the neural control of locomotion and is provided by the visual system, the vestibular system and the somatosensory system.

Visual system
Visual inputs play a critical role in locomotor behavior. They aid in identifying and following a chosen path, avoiding obstacles, and combine with vestibular inputs to maintain orientation in space (Rossignol).

The role of vision during straight path, unperturbed walking is minimal. However, one typically encounters changes in the surface being walked on, such as variations in the grade of the surface (i.e. hills or stairs), or the quality of the surface (i.e. ice or mud). In order to compensate for these changes, the locomotor system uses visual feedback in order to produce a control feed-forward control strategy to anticipate these changes, and adjust the motor command accordingly in order to maintain stability.

Vestibular system
Maintaining balance and a sense of spatial orientation is essential for locomotion. The vestibular system relays information from the periphery to vestibular nuclei in the brainstem via the vestibulocochlear nerve. This sensory signal has been shown to modulate locomotor output via vestibulospinal pathways. Signals from the vestibular nuclei project directly to alpha motor neurons and interneurons that form CPGs in the spinal locomotor system, thus modulating locomotor output. It is also thought that vestibular nuclei project to the medial reticular formation, so as to modulate the command signal of the reticulospinal pathway, which receives input from the mesencephalic locomotor region.

Somatosensory system
Sensory feedback from the limbs to the nervous system has been shown to influence the phase of the gait cycle, specifically the duration of the stance or support phase. The speed of locomotion in the limbs of chronic spinal and decerebrate cats will adapt in response to changes in the treadmill speed. Presumably then, in the absence of descending input from higher brain centers, this adaptation can be attributed to sensory feedback provided by the limbs. Two sensory inputs have been implicated in terminating the stance phase and initiating the swing phase. The stretch-sensitive Ia afferents of the hip flexor muscles, which are activated during hip extension, as well as the force-sensitive Ib afferents arising from the Golgi tendon organ of the ankle extensor muscles (calcaneal or Achilles tendon). It should be noted however that the extent to which these two pathways contribute to transitions from the stance to the swing is unclear. In chronic spinal cats, it has been shown that activation of the afferents of the hip flexor muscles is essential for the transition between stance and swing phases, whereas in decerebrate cats, a decrease in activity of the Ib afferents of the ankle extensors (due to the unloading of the limb) is responsible for the transition. Given these observations, the role of these two sensory mechanisms in an intact animal is unclear, but it has been suggested that both play a role in phase transitions of gait.

In addition to sensory feedback arising from the tendons and muscles of the limb, cutaneous afferents have also shown to influence locomotor patterns (Forssberg H, Grillner S, and Rossignol S., 1977, Forssberg H, 1979). The main role of cutaneous feedback has been suggested to be in the correct placement of the foot and adjusting the position of the limb in response to a perturbation. Several studies have shown the contribution of cutaneous afferents to locomotor output to be phase dependent (whether the limb is in the stance or swing phase), task dependent (walking forward or backward) and site dependent (whether the stimulus is applied to the dorsal or ventral aspect of the foot). A classic example of this is the stumbling corrective reaction. In cats for example, if a mechanical stimulus is applied to the dorsum of the paw during the swing phase, such as if the paw struck an unexpected obstacle, a rapid flexion of the knee joint would occur to withdraw the limb, followed by flexion of the hip and ankle joints to step over the object. In humans, a similar reaction is observed if the mechanical stimulus is applied in early swing; there is a rapid response in the biceps femoris muscle to produce knee flexion followed by activation of rectus femoris to flex the hip and to extend the knee. This response effectively withdraws the limb to clear the object and then places the foot in front of it. However, if the stimulus is applied late in the swing phase, a strategy is used not to attempt to step over the object, but rather to lower the foot back to the ground as soon as possible to maintain an upright stance.