Locomotion

A Complex Sequence of Muscle Contractions Is Required for Stepping

The Motor Pattern for Stepping Is Organized at the Spinal Level

Contraction in Flexor and Extensor Muscles of the Hind Legs Is Controlled by Mutually Inhibiting Networks

Central Pattern Generators Are Not Driven by Sensory Input

Spinal Networks Can Generate Complex Locomotor Patterns

Sensory Input from Moving Limbs Regulates Stepping

Proprioception Regulates the Timing and Amplitude of Stepping

Sensory Input from the Skin Allows Stepping to Adjust to Unexpected Obstacles

Descending Pathways Are Necessary for Initiation and Adaptive Control of Stepping

Pathways from the Brain Stem Initiate Walking and Control Its Speed

The Cerebellum Fine-Tunes Locomotor Patterns by Regulating the Timing and Intensity of Descending Signals

The Motor Cortex Uses Visual Information to Control Precise Stepping Movements

Planning and Coordination of Visually Guided Movements Involves the Posterior Parietal Cortex

Human Walking May Involve Spinal Pattern Generators

An Overall View

THE ABILITY TO MOVE IS ESSENTIAL for the survival of animals. Although many forms of locomotion have evolved—swimming, flying, crawling, and walking—all use rhythmic and alternating movements of the body or appendages. This rhythmicity makes locomotion appear to be repetitive and stereotyped. Indeed, locomotion is controlled automatically at relatively low levels of the central nervous system without intervention by higher centers. Nevertheless, locomotion often takes place in environments that are either unfamiliar or present unpredictable conditions. Locomotor movements must therefore be continually modified, usually in a subtle fashion, to adapt otherwise stereotyped movement patterns to the immediate surroundings.

The study of the neural control of locomotion must address two fundamental questions. First, how do assemblies of nerve cells generate the rhythmic motor patterns associated with locomotor movements? Second, how does sensory information adjust locomotion to both anticipated and unexpected events in the environment? In this chapter we address both of these questions by examining the neural mechanisms controlling walking.

Although most information on neural control of walking has come from studying the cat’s stepping movements, important insights have also come from studies of other animals as well as rhythmic behaviors other than locomotion. Therefore, we shall also consider the more general question of how rhythmic motor activity can be generated and sustained by networks of neurons.

Several critical insights into the neural mechanisms controlling quadrupedal stepping were obtained nearly a century ago when it was found that removing the cerebral hemispheres in dogs did not abolish walking—decerebrate animals are still able to walk spontaneously. One animal was observed to rear itself up in order to rest its forepaws on a gate at feeding time. It was soon discovered that stepping of the hind legs could be induced in cats and dogs after complete transection of the spinal cord. The stepping movements in these spinal preparations (Box 36-1) are similar to normal stepping. Nonrhythmic electrical stimulation of the cut cord elicits stepping at a rate related to the intensity of the stimulating current. Another important early observation was that passive movement of a limb by the experimenter could initiate stepping movements in spinal cats and dogs, suggesting that proprioceptive reflexes are crucial in regulating the movements.

Finally, in 1911 Thomas Graham Brown discovered that rhythmic, alternating contractions could be evoked in deafferented hind leg muscles immediately after transection of the spinal cord. He therefore proposed the concept of the half-center, whereby flexors and extensors inhibit each other reciprocally, giving rise to alternating stepping movements. Four conclusions can be drawn from these early studies.

1. Supraspinal commands are not necessary for producing the basic motor pattern for stepping.

2. The basic rhythmicity of stepping is produced by neuronal circuits contained entirely within the spinal cord.

3. The spinal circuits can be modulated by tonic descending signals from the brain.

4. The spinal pattern-generating networks do not require sensory input but nevertheless are strongly regulated by input from limb proprioceptors.

For almost half a century following these early studies few investigations were aimed at establishing the neural mechanisms for walking. Instead, research on motor systems focused on the organization of spinal reflex pathways and the mechanisms of synaptic integration within the spinal cord (see Chapter 35). Modern research on the neural control of locomotion dates from the 1960s and two major experimental successes. First, rhythmic patterns of motor activity were elicited in spinal animals by the application of adrenergic drugs. Second, walking on a treadmill was evoked in decerebrate cats by electrical stimulation of a small region in the brain stem.

At about the same time electromyographic recordings from numerous hind leg muscles in intact cats during unrestrained walking revealed the complexity of the locomotor pattern and brought to prominence the question of how spinal reflexes are integrated with intrinsic spinal circuits to produce the locomotor pattern. Soon thereafter, investigations of stepping in spinal cats demonstrated the similarity of locomotor patterns in spinal preparations and intact animals, thus firmly establishing the idea that the motor output for locomotion is produced primarily by a neuronal system in the spinal cord.

A Complex Sequence of Muscle Contractions Is Required for Stepping

For the purpose of examining the patterns of muscle contraction during locomotion, the step cycle in cats and humans can be divided into four distinct phases: flexion (F), first extension (E₁), second extension (E₂), and third extension (E₃) (Figure 36-2A). The F and E₁ phases occur during the time the foot is off the ground (swing), whereas E₂ and E₃ occur when the foot is in contact with the ground (stance).

Figure 36-2 Stepping is produced by complex patterns of contractions in leg muscles.

A. The step cycle is divided into four phases: the flexion (F) and first extension (E,) phases occur during swing, when the foot is off the ground, whereas second extension (E₂) and third extension (E₃) occur during stance, when the foot contacts the ground. Second extension is characterized by flexion at the knee and ankle as the leg begins to bear the animal’s weight. The contracting knee and ankle extensor muscles lengthen during this phase. (Adapted, with permission, from Engberg and Lundberg 1969.)

B. Profiles of electrical activity in some of the hind leg flexor and extensor muscles in the cat during stepping. Although flexor and extensor muscles are generally active during swing and stance, respectively, the overall pattern of activity is complex in both timing and amplitude. (IP, iliopsoas; LG and MG, lateral and medial gastrocnemius; PB, posterior biceps; RF, rectus femoris; Sart_m and Sart_a, medial and anterior sartorius; SOL, soleus; ST, semitendinosus; TA, tibialis anterior; VL, VM, and VI, vastus lateralis, medialis, and intermedialis.)

Swing commences with flexion at the hip, knee, and ankle (the F phase). Approximately midway through swing the knee and ankle begin to extend while the hip continues to flex (the E₁ phase). Extension at the knee and ankle during E₁ moves the foot ahead of the body and prepares the leg to accept weight in anticipation of foot contact at the onset of stance. During early stance (the E₂ phase) the knee and ankle joints flex, even though extensor muscles are contracting strongly. A lengthening contraction of ankle and knee extensor muscles occurs because weight is being transferred to the leg. The spring-like yielding of these muscles as weight is accepted allows the body to move smoothly over the foot, and is essential for establishing an efficient gait. During late stance (the E₃ phase) the hip, knee, and ankle all extend to provide a propulsive force to move the body forward.

The rhythmic movements of the legs during stepping are produced by contractions of many muscles. In general, contractions of flexor muscles occur during the F phase, whereas contractions of extensor muscles occur during one or more of the E phases. However, the timing and amounts of activity are different in different muscles (Figure 36-2B). For example, a hip flexor muscle (iliopsoas) contracts continuously during the F and E₁ phases, whereas a knee flexor muscle (semitendinosus) contracts briefly at the beginning of the F and E₂ phases. Another complexity is that some muscles contract during both swing and stance. Thus the motor pattern for stepping is not merely alternating flexion and extension at each joint, but a complex sequence of muscle contractions, each precisely timed and scaled to achieve a specific task in the act of locomotion.

The Motor Pattern for Stepping Is Organized at the Spinal Level

Transection of the spinal cord of quadrupeds initially causes complete paralysis of the hind legs. It does not, however, permanently abolish the capacity of hind legs to make stepping movements: Hind leg stepping often recovers spontaneously over a period of a few weeks, particularly if the transection is made in young animals. Recovery of stepping in adult cats can be facilitated by daily training on a treadmill evoked by nonspecific cutaneous stimulation of the perineal region.

Electromyographic records of the hind leg muscles of chronic spinal cats during stepping are quite similar to those of normally walking animals. Many of the reflex responses that occur in normal animals can also be evoked in spinal animals. Spinal animals are not, however, able to maintain balance on the treadmill. Adequate control of balance requires descending signals from brain stem centers, such as the vestibular nuclei.

Contraction in Flexor and Extensor Muscles of the Hind Legs Is Controlled by Mutually Inhibiting Networks

From the studies by Graham Brown early in the 20th century we know that the isolated spinal cord can generate rhythmic bursts of reciprocal activity in flexor and extensor motor neurons of the hind legs even in the absence of sensory input (Figure 36-3). Graham Brown proposed that contractions in the flexor and extensor muscles are controlled by two systems of neurons, or half-centers, that mutually inhibit each other (Figure 36-4B).

Figure 36-3 Rhythmic activity for stepping is generated by networks of neurons in the spinal cord. The existence of such spinal networks was first demonstrated by Thomas Graham Brown in 1911. Graham Brown developed an experimental preparation system in which dorsal roots were cut so that sensory information from the limbs could not reach the spinal cord. An original record from Graham Brown’s study shows that rhythmic alternating contractions of ankle flexor (tibialis anterior) and extensor (gastrocnemius) muscles begin immediately after transection of the spinal cord.

According to Graham Brown, activity alternates between half-centers because of fatigue of the inhibitory connections. For example, if two half-centers receive tonic excitatory input, and the flexor half-center receives the stronger input, the flexor muscles will contract while the extensor half-center is inhibited. Then, as the inhibitory output fatigues, the extensor half-center’s output will increase, causing inhibition of the flexor half-center and contraction of the extensor muscles until its inhibitory output fatigues. Thus the flexor and extensor muscles controlled by the two half-centers will alternately contract and relax as long as the half-centers receive sufficient tonic excitatory input.

The half-center hypothesis was supported by studies in the 1960s on the effects in spinal cats of the drug L-dihydroxyphenylalanine (L-DOPA), a precursor of the monoamine transmitters dopamine and norepinephrine. After the cats were treated with L-DOPA, brief trains of electrical stimuli were applied to small-diameter sensory fibers from skin and muscle. These trains of stimuli evoked long-lasting bursts of activity in either flexor or extensor motor neurons, depending on whether ipsilateral or contralateral nerves were stimulated. The afferents producing these effects are collectively termed flexor reflex afferents. Additional administration of nialamide, a drug that prolongs the action of norepinephrine released in the spinal cord, often resulted in short sequences of rhythmic reciprocal activity in flexor and extensor motor neurons (Figure 36-4A).

Figure 36-4 Reciprocal activity in flexor and extensor motor neurons.

A. High-threshold cutaneous and muscle afferents called flexor reflex afferents (FRA) were electrically stimulated in spinal cats treated with L-DOPA (L-dihydroxyphenylalanine) and nialamide. Brief stimulation of ipsilateral FRAs evoked a short sequence of rhythmic activity in flexor and extensor motor neurons. (Adapted, with permission, from Jankowska et al. 1967a.)

B. Interneurons in the pathways mediating long-latency reflexes from the ipsilateral and contralateral FRAs mutually inhibit one another. This “half-center” organization of the flexor and extensor interneurons likely mediates rhythmic stepping.

C. Stimulation of the ipsilateral FRA evokes a delayed, long-lasting burst of activity in the half-center interneurons located in the intermediate region of the gray matter. (Adapted, with permission, from Jankowska et al. 1967b.)

The system of interneurons generating flexor bursts was found to inhibit the system of interneurons generating the extensor bursts, and vice versa (Figure 36–4B). This organizational feature is consistent with Graham Brown’s theory that mutually inhibiting “half-centers” produce the alternating burst activity in flexor and extensor motor neurons. The interneurons mediating the burst patterns arising from stimulation of the flexor reflex afferents have not been fully identified but they may include interneurons in the intermediate region of the gray matter in the sixth lumbar segment. Interneurons in this region produce prolonged bursts of activity in response to brief stimulation of either ipsilateral or contralateral flexor reflex afferents in spinal cats treated with L-DOPA (Figure 36-4C).

Central Pattern Generators Are Not Driven by Sensory Input

Neuronal spinal networks capable of generating rhythmic motor activity in the absence of rhythmic input from peripheral receptors are termed central pattern generators(Box 36-2). Largely because the mammalian nervous system is so complex, we lack detailed information on the neuronal circuitry and mechanisms for rhythm generation by central pattern generators in the mammalian spinal cord. However, we have considerable knowledge about the cellular, synaptic, and network properties of central pattern generators in invertebrates and lower vertebrates, which have less complex nervous systems than mammals. For example, the analysis by Sten Grillner of the central pattern generator controlling swimming in the lamprey has provided considerable insight into the mechanisms of rhythm generation in vertebrate motor systems (Box 36-3).