Supraspinal Locomotor Centers Research Articles

Sensory cortical control of movement

Walking in our complex environment requires continual higher order integrated spatiotemporal information. This information is processed in the somatosensory cortex, and it has long been presumed that it influences movement via descending tracts originating from the motor cortex. Here we show that neuronal activity in the primary somatosensory cortex tightly correlates with the onset and speed of locomotion in freely moving mice. Using optogenetics and pharmacogenetics in combination with in vivo and in vitro electrophysiology, we provide evidence for a direct corticospinal pathway from the primary somatosensory cortex that synapses with cervical excitatory neurons and modulates the lumbar locomotor network independently of the motor cortex and other supraspinal locomotor centers. Stimulation of this pathway enhances speed of locomotion, while inhibition decreases locomotor speed and ultimately terminates stepping. Our findings reveal a novel pathway for neural control of movement whereby the somatosensory cortex directly influences motor behavior, possibly in response to environmental cues.

Glutamatergic neurons of the gigantocellular reticular nucleus shape locomotor pattern and rhythm in the freely behaving mouse.

Because of their intermediate position between supraspinal locomotor centers and spinal circuits, gigantocellular reticular nucleus (GRN) neurons play a key role in motor command. However, the functional contribution of glutamatergic GRN neurons in initiating, maintaining, and stopping locomotion is still unclear. Combining electromyographic recordings with optogenetic manipulations in freely behaving mice, we investigate the functional contribution of glutamatergic brainstem neurons of the GRN to motor and locomotor activity. Short-pulse photostimulation of one side of the glutamatergic GRN did not elicit locomotion but evoked distinct motor responses in flexor and extensor muscles at rest and during locomotion. Glutamatergic GRN outputs to the spinal cord appear to be gated according to the spinal locomotor network state. Increasing the duration of photostimulation increased motor and postural tone at rest and reset locomotor rhythm during ongoing locomotion. In contrast, photoinhibition impaired locomotor pattern and rhythm. We conclude that unilateral activation of glutamatergic GRN neurons triggered motor activity and modified ongoing locomotor pattern and rhythm.

Walking in orthostatic tremor modulates tremor features and is characterized by impaired gait stability

Primary orthostatic tremor (OT) is characterized by high-frequency lower-limb muscle contractions and a disabling sense of unsteadiness while standing. Patients consistently report a relief of symptoms when starting to ambulate. Here, we systematically examined and linked tremor and gait characteristics in patients with OT. Tremor and gait features were examined in nine OT patients and controls on a pressure-sensitive treadmill for one minute of walking framed by two one-minute periods of standing. Tremor characteristics were assessed by time-frequency analysis of surface EMG-recordings from four leg muscles. High-frequency tremor during standing (15.29 ± 0.17 Hz) persisted while walking but was consistently reset to higher frequencies (16.34 ± 0.25 Hz; p < 0.001). Tremor intensity was phase-dependently modulated, being predominantly observable during stance phases (p < 0.001). Tremor intensity scaled with the force applied during stepping (p < 0.001) and was linked to specific gait alterations, i.e., wide base walking (p = 0.019) and increased stride-to-stride fluctuations (p = 0.002). OT during walking persists but is reset to higher frequencies, indicating the involvement of supraspinal locomotor centers in the generation of OT rhythm. Tremor intensity is modulated during the gait cycle, pointing at specific pathways mediating the peripheral manifestation of OT. Finally, OT during walking is linked to gait alterations resembling a cerebellar and/or sensory ataxic gait disorder.

Subthalamic nucleus stimulation improves Parkinsonian gait via brainstem locomotor centers

Subthalamic deep brain stimulation (STN-DBS) can ameliorate gait disturbances in Parkinson's disease (PD). Using motor imagery and positron emission tomography (PET), we investigated how STN-DBS interacts with supraspinal locomotor centers in PD. Ten PD patients with bilateral STN-DBS actually walked or stood still under STN-DBS ON or OFF conditions. Directly thereafter, subjects imagined walking or standing while changes in regional cerebral blood flow were measured by PET. Independent of STN-DBS, imagined walking distance correlated with imagery duration. Compared with STN-DBS OFF, STN-DBS ON improved actual gait and increased imagined walking distance. Imagery of gait (vs. stance) induced activity in the supplementary motor area and the right superior parietal lobule for both STN-DBS conditions. The improvement of imagined gait during STN-DBS ON led to activity changes in the pedunculopontine nucleus/mesencephalic locomotor region (PPN/MLR). Data suggest that STN-DBS improves Parkinsonian gait by modulating PPN/MLR activity.

Functional disturbance of the locomotor network in progressive supranuclear palsy

To determine pathologic regulations and potential compensatory mechanisms in the supraspinal locomotor network of patients with progressive supranuclear palsy (PSP) by investigation of brain activation during walking and correlation to gait performance. Twelve patients with PSP were scanned with [18F]-FDG-PET during walking and at rest as has been described earlier. Results were compared to age-matched healthy controls (n = 12). The major results were as follows. (1) At rest, the regional cerebral glucose metabolism (rCGM) in the supraspinal locomotor centers, i.e., the prefrontal cortex, the subthalamic nucleus, and the pedunculopontine/cuneiform nucleus complex, was reduced in PSP. (2) Severity of gait impairment, measured by gait velocity, step length, and progressive supranuclear palsy rating scales/gait, correlated with decrease of rCGM in the prefrontal cortex and subthalamic nucleus. (3) Accordingly, during walking functional activation of the prefrontal cortex, the subthalamic nucleus, the pedunculopontine/cuneiform nucleus complex, and the thalamus was reduced in patients with PSP compared to controls. (4) The precentral gyrus and the vermal cerebellum were activated more strongly during locomotion in PSP. Gait impairment in PSP is especially associated with dysfunction of the indirect, modulatory prefrontal-subthalamic-pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar drive shows increased activity in PSP. The latter can be interpreted as an attempt of compensation, but may also contribute to a stereotyped gait pattern in PSP.

Hindlimb movement in the cat induced by amplitude-modulated stimulation using extra-spinal electrodes

Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of the L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury.

Imaging human supraspinal locomotor centers in brainstem and cerebellum

An erect posture with bipedal locomotion is a characteristic feature of humans compared to other mammals. Most of our knowledge about the hierarchical network of supraspinal locomotor centers derives from animal experiments, mainly in the cat. We posed the question of whether evolutionary transition from quadrupedal to bipedal locomotion – with associated change of foreleg function – caused reorganization of these supraspinal locomotor centers. Using functional magnetic resonance imaging, we identified separate and distinct cerebellar and brainstem BOLD signal increases related to posture and gait during mental imagery of standing, walking, and running in healthy volunteers ( n = 26). Comparison with the locomotion centers in the cat showed that these activations include the pacemakers for gait initiation and speed regulation in the interfastigial cerebellum and bilateral midbrain tegmentum (cerebellar and mesencephalic locomotor regions), their descending target regions in the pontine reticular formation, and the rhythm generators in the cerebellar vermis and paravermal cortex. Moreover, during mental imagery of stance, a BOLD signal increase was observed in the dorsal pons, reflecting an activation of the dorsal tegmental field, a locomotion-suppressing site in the cat. These results support the view that the organization of supraspinal locomotor centers was preserved during the transition to bipedal locomotion. The clinical relevance of these centers has so far been largely neglected. However, Parkinson's disease, for example, is associated with reduced cell counts in the pedunculopontine nucleus, a part of the mesencephalic locomotor region. This association suggests that deep brain stimulation of locomotion centers may provide new therapeutic approaches for common gait disorders.

Comment on Point:Counterpoint "Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise in humans"

The following letters are in response to the Point:Counterpoint series “Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise in humans” that appeared in the March issue (vol. 100: 1077–1083, 2006; <http://jap.physiology.org/content/vol100/issue3

Comment on Point:Counterpoint “Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise in humans”

The following letters are in response to the Point:Counterpoint series “Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise in humans” that appeared in the March issue (vol. 100: 1087–1083, 2006; <http://jap.physiol.org/content/vol100/issue3/

The Last Word: Point:Counterpoint authors respond to commentaries on “Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise in humans”

To the Editor : The reactions to the debate on the role of supraspinal (hypothalamic/mesencephalic) locomotor centers (SLC) in controlling ventilation during exercise show that this question is far from futile ([3][1]). Many respiratory physiologists and neurophysiologists are still accepting the

Point:Counterpoint: Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exercise

This series of debates was initiated for the Journal of Applied Physiology because we believe an important means of searching for truth is through debate where contradictory viewpoints are put forward. This dialectic process whereby a thesis is advanced, then opposed by an antithesis, with a

Posthyperventilation breathing patterns after active hyperventilation in man.

Posthyperventilation breathing patterns after active hyperventilation in man.

Analysis of factors concerned in regulation of breathing in exercise.

ArticlesANALYSIS OF FACTORS CONCERNED IN REGULATION OF BREATHING IN EXERCISEFred S. GrodinsFred S. GrodinsPublished Online:01 Apr 1950https://doi.org/10.1152/physrev.1950.30.2.220MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Download PDF FiguresReferencesRelatedInformation Cited ByShort-term modulation of the exercise ventilatory response in young menHelen E. Wood, Gordon S. Mitchell, and Tony G. Babb1 January 2008 | Journal of Applied Physiology, Vol. 104, No. 1Point:Counterpoint: Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exerciseTony G. Waldrop, and Gary A. Iwamoto1 March 2006 | Journal of Applied Physiology, Vol. 100, No. 3Invited Review: Neuroplasticity in respiratory motor controlGordon S. Mitchell, and Stephen M. Johnson1 January 2003 | Journal of Applied Physiology, Vol. 94, No. 1The physiological control of respirationMolecular Aspects of Medicine, Vol. 13, No. 6Allometry of respiratory and haematological parameters of arctic mammalComparative Biochemistry and Physiology Part A: Physiology, Vol. 64, No. 3Addendum1 January 1975 | Annals of the ICRP/ICRP Publication, Vol. OS_23, No. 1Human core temperature increase as a stimulus to breathing during moderate exerciseRespiration Physiology, Vol. 21, No. 2Effect of body temperature on the ventilatory response to exerciseRespiration Physiology, Vol. 8, No. 3Ventilatory responses to hind limb exercise in anesthetized cats and dogsRespiration Physiology, Vol. 6, No. 1Models of the regulation of external respiration in mammals. Problems and promisesComputers and Biomedical Research, Vol. 1, No. 1Ventilatory responses to intravenous and inspired carbon dioxide in anesthetized catsRespiration Physiology, Vol. 2, No. 1The influence of sodium amytal on the respiratory abnormalities of anxious psychiatric patientsJournal of Psychosomatic Research, Vol. 5, No. 1RESPIRATORY ADAPTATIONThe Lancet, Vol. 264, No. 6850 More from this issue > Volume 30Issue 2April 1950Pages 220-239 https://doi.org/10.1152/physrev.1950.30.2.220PubMed15424035History Published online 1 April 1950 Published in print 1 April 1950 Metrics