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Role of Motor Cortex in Control of Walking*
Irina N. Beloozerova,
PhD
Mikhail G. Sirota, PhD
Division of Neurobiology, Barrow Neurological
Institute, St. Joseph's Hospital and Medical Center, Phoenix,
Arizona
*Courtesy of Irina N. Beloozerova, PhD
The Beloozerova Laboratory
Irina Beloozerova received her PhD in
physiology from the Lomonosov University in Moscow, Russia, for her
studies on the role of the motor cortex in the control of walking.
She then studied the physiology of the spinal cord with Serge
Rossignol at the University of Montreal, Canada, and the physiology
of the somatosensory cortex with Harvey Swadlow at the University
of Connecticut. Mikhail Sirota obtained his PhD in physiology
from the Lomonosov University in Moscow, Russia, where he
studied the mechanisms of initiation of walking in the
laboratory of Mark Shik. He then headed the Laboratory of
Microgravity Neurophysiology at the Institute of Biomedical
Problems in Moscow, Russia and studied the effects of
weightlessness in outer space on motor coordination. Zinayida
Tamarova obtained her PhD in physiology from the A. A. Bogomoletz
Institute of Physiology, in Kiev, Ukraine, working in the
laboratory of Platon Kostuk on the spinal mechanism underlying
visceromotor reflexes. She then studied mechanisms of synaptic
transmission in the spinal cord and influences of higher brain
centers on motoneurons with Alexander Shapovalov in Leningrad,
Russia and central mechanisms of pain with Yury Limansky in Kiev,
Ukraine.
Walking includes voluntary components that are necessary to
overcome obstacles and to change directions. In cats and humans,
these movements are not possible without the contribution of the
motor cortex. One focus of our laboratory is the role of the motor
cortex in the control of walking. The activity of the motor cortex
of cats was recorded during simple and complex (i.e., involving
overcoming obstacles) walking. The activity of the motor cortex
changed dramatically when cats had to negotiate obstacles compared
to simple walking conditions. Lesions to the motor cortex made cats
incapable of negotiating obstacles correctly. During complex
walking it appears that the activity of the motor cortex contains
commands addressed to the spinal cord and that these commands
adjust the spinal locomotor mechanisms to specific structures of
the pathway.
Key Words:
locomotion, motor
cortex
Abbreviations
used: SD, standard deviation; TTX, tetrodotoxin
Walking includes voluntary components that are necessary for
overcoming obstacles and for changing the direction of movements.
The point at which to step often must be chosen carefully. The
system of reception with which the spinal cord is equipped is
sufficient to ensure walking on a flat surface; however, it is
incapable of adapting movements to a complex environment.13 Natural
locomotion is impossible without the contribution of supraspinal
centers to control stepping movements. One focus of research in our
laboratory is the involvement of the motor cortex in the control of
walking in a complex environment.
Commands from supraspinal motor centers reach
the spinal cord by various descending tracts.[1,4,5] The activity
of nerve cells that contribute their long branches, axons, to
the reticulospinal, vestibulospinal, rubrospinal, and pyramidal
tracts was studied in walking animals. [2,3,7,8,15,16,17] The
activity of these neurons is modulated rhythmically, and
the modulation is related to the stepping rhythm. The activity
of the motor cortex changes during voluntary movements and, in some
cases, before the movements begin.[9-12,14,19] Injury to the motor
cortex damages the capacity to perform some voluntary limb
movements or at least greatly interferes with the performance of
these movements.
We recorded the activity of neurons in the
motor cortex in cats during walking. Two conditions were tested:
(1) walking on a flat horizontal surface (simple walking) and (2)
walking while overcoming various obstacles (complex walking). The
latter requires visual inspection of the environment and
appropriate adaptation of steps. We compared the activity of
neurons of the motor cortex under simple and complex conditions,
assuming that the difference in that activity would be related to
the difference in the tasks, thereby revealing the cortical
"voluntary" motor command underlying precise stepping.
Figure 1. The experimental box was divided into two corridors;
barriers or a horizontal
ladder was placed in one of them. Cats were trained to pass through
the corridors sequen-
tially and repeatedly. The activity of the cortical motor neurons
was recoded as the cat
walked along the corridors.
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Methods
Positive reinforcement (food) was used to adapt cats to the
experimental situation and to engage them in locomotor
behavior.[18,20] A rectangular enclosure (2.5 m x 0.5 m) served as
an experimental chamber. A longitudinal wall divided the box into
two corridors through which the cats passed sequentially and
repeatedly in either direction. In one corridor the floor was flat;
the other corridor contained a horizontal ladder or a set of
barriers (Fig. 1).
Once trained, the cat underwent surgery during
which a plastic base was fixed to the skull. A microdriver and an
amplifier were then attached to the base. The bone above the
motor cortex was replaced with a plastic plate that had about 100
small holes prefilled with sterile bone wax. Subsequently, the
recording electrode was introduced through the holes into the
brain.
The activity of a neuron during a step was
assessed as was its activity before locomotion. For analysis of
neuronal activity, a step was divided into 10 intervals, and a
postevent time histogram of spike distribution throughout the step
was obtained for 20 to 200 successive steps. The difference between
the maximum and minimum firing frequency associated with a step
divided by the mean frequency was used as an index to the depth of
rhythmic step-related modulation.
Figure 2. Examples of activity of two neurons in the motor cortex
(A and B) before
and during simple walking. The action potentials are depicted as
vertical lines. The
bottom traces show the stance and swing phases of a forelimb
(deflection down and
up, respectively).
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Results
Simple Walking
During standing, the discharge frequency of
motor cortical neurons was 1 to 30 impulses (mean ± SD, 9.8
± 1). During the transition from standing to locomotion, the
average activity of 36% of the neurons increased about two-fold and
it increased three to five-fold in 20%. We analyzed the activity of
neurons immediately before the first step, defined as the number of
spikes in each 100 ms interval during the 2 s preceding the first
step. During this period the activity of 70% of the neurons
remained unchanged, but the activity of 25% of the neurons
increased (Fig. 2).
The activity of 252 neurons in the motor
cortex was recorded during simple walking. The activity of 89% of
these neurons was modulated in relation to the stepping movements;
that is, activity increased during one step phase and decreased
during the next (Fig. 2). The maximum activity in 65% of the
"modulated" neurons coincided with the swing phase of the
contralateral forelimb (as in Fig. 2A) and in 35% of the neurons,
with the stance phase (as in Fig. 2B). The mean depth of frequency
modulation was 25 ± 2 %.
Figure 3. (A) Barrier arrangement and corresponding (B and C)
neronal activity showing
changes in the activity of a cortical motor neuron when limb
positions are restricted dur-
ing stepping. (A) A cat initially walked with no obstacles. Then
the barriers (70-mm high,
interbarrier distance as indicated) were arranged in the box. (B)
The action potentials
are depicted as vertical lines. The bottom traces show the stance
(St) and swing (Sw)
phases of a forelime (deflection down and up, respectively). (C)
The corresponding phase
distributions of neuronal activity. Dashed lines show the level of
activity during standing.
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Complex
Walking
Overstepping
Barriers. The possible positions of the cat’s
feet on the floor were restricted by arranging barriers along the
cat's path. The height of the barriers was 70 mm, and the distance
between successive barriers was 250 mm (i.e., equal to an average
cat's step; Fig. 3). To walk along the box, the cat had to step
between the barriers.
Under these conditions, the activity of 68
neurons in the motor cortex was recorded. In 79% of the neurons,
the average activity during walking with barriers differed from
that during simple walking: Activity increased in 50% and decreased
in 29%. The depth of frequency modulation changed in 84% of the
neurons, increasing in 59% and decreasing in 25%. In 91% of cases,
the phases of maximum activity were the same during both simple and
complex locomotion (Fig. 3).
We also tested the activity of the same
neurons with smaller interbarrier intervals (i.e., the cats had to
step with greater accuracy). In all neurons tested, the average
activity and depth of modulation increased as the interbarrier
interval decreased (Fig. 3).
Walking on Rungs of
a Horizontal Ladder. The horizontal ladder had 50-mm
wide rungs, and the distance between successive rungs was 250 mm.
When the cats walked on the ladder, the possible position of a limb
landing on the supporting surface was restricted to the rungs. In
contrast, during the previous test conditions, cats could place
their feet anywhere between the barriers.
The activity of 108 neurons in the motor
cortex was recorded while cats walked along the ladder. Compared to
simple walking, walking on the ladder changed the average level of
activity in 81% of the neurons: Activity increased in 71% and
decreased in 10%. The depth of frequency modulation changed in 80%
of the neurons: Modulation increased in 56% of the neurons and
decreased in 24% of the neurons: The phases of maximum and minimum
activity persisted in most neurons.
Effects of Lesioning
or Chemical Inactivation of the Motor Cortex on
Walking
Neither bilateral permanent lesions of the
motor cortex, nor reversible inactivation by cooling, nor the
neurotoxin TTX hampered simple walking. In contrast, cats with a
lesion or inactivated motor cortex could no longer step over
obstacles (they knocked them over). They also could not walk on the
ladder (they missed the rungs). After lesioning, their inability to
perform a complex walk persisted 5 to 7 days. Attempts at walking
then became more successful. After about 1 week, cats managed to
perform the complex walking tasks without making mistakes. This
finding suggests that some other undamaged brain structures assumed
the function of the motor cortex after injury to control the
accuracy of stepping.
Discussion
Simple Walking
In many neurons a tonic change in activity was
observed before a cat took its first step. This change seems to be
associated with the postural adjustments involved in the
transition from standing to locomotion. When a cat walked on the
flat horizontal surface with no obstacles, the activity of most
motor cortical cells was modulated rhythmically, with the
modulation related to the rhythm of the stepping movements. Various
neurons in the motor cortex showed maximum activity during various
phases of a step, but most neurons were most active during the
swing phase of the corresponding limb.
What is the source of the rhythmic signal
modulation of the activity of neurons in the motor cortex?
Armstrong and Drew[3] blocked nerves with novocaine and found that
elimination of somatic sensation did not abolish the rhythmic
modulation of the neurons. This finding suggested that the source
of modulatory signals is not at the periphery but rather involves
central neuronal mechanisms. In experiments with exercise belt
walking,[4] neurons of tracts descending from the brainstem to the
spinal cord were modulated rhythmically in relation to the stepping
cycle. The source of their modulatory signals proved to be
the spinal neuronal mechanism generating the stepping rhythm.
Spinal influences on these neurons are mediated by the cerebellum
-- another brain structure closely involved with the control of
movements. Neurons in the motor cortex likely receive modulatory
commands via the same route because their rhythmical modulation
decreased considerably after a nucleus that mediates cerebellar
influences on the motor cortex was destroyed.[6]
Complex
Walking
Our main finding is that the pattern of
activity of most cortical motor neurons changed dramatically when
cats had to perform stepping movements with accuracy. The
information concerning the peculiarities of the walking pathway was
obtained via the visual system. Therefore, the activity of neurons
in the motor cortex changes considerably when the visual system is
involved in the control of walking.
A lesion to the motor cortex renders an animal
incapable of performing space-linked stepping under the control of
vision. Consequently, it seems likely that the activity of neurons
in the motor cortex involving pronounced rhythmical modulation, as
observed in our experiments, constitutes the cortical commands
addressed to the spinal cord. These commands suitably adjust the
operation of the spinal mechanisms to external conditions.
Understanding the formation and the content of these commands may
help in the design of brain-machine interfaces that will help
people with damage to the motor cortex or corticospinal
pathway.
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