Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2 mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

Effects of postural-control training with different sensory reweightings in a patient with body lateropulsion: a single-subject design study.

INTRODUCTION: Body lateropulsion (BL) is an active lateral tilt of the body during standing or walking that is thought to be affected by a lesion of the vestibulospinal tract (VST) and the subjective visual vertical (SVV) tilt. Interventions for BL have not been established. OBJECTIVE: We examined the effects of postural-control training with different sensory reweighting on standing postural control in a patient with BL. METHODS: The patient had BL to the left when standing or walking due to a left-side medullary and cerebellar infarct. This study was a single-subject A-B design with follow-up: Phase A was postural-control training with visual feedback; phase B provided reweighting plantar somatosensory information. Postural control, VST excitability, and SVV were measured. RESULTS: At baseline and phase A, the patient could not stand with eyes-closed on a rubber mat, but became able to stand in phase B. The mediolateral center of pressure (COP) position did not change significantly, but the COP velocity decreased significantly during phase B and the follow-up on the firm surface. VST excitability was lower on the BL versus the non-BL side, and the SVV deviated to the right throughout the study. CONCLUSION: Postural-control training with reweighting somatosensory information might improve postural control in a patient with BL.

Gait control by the frontal lobe.

The frontal lobe is crucial and contributes to controlling truncal motion, postural responses, and maintaining equilibrium and locomotion. The rich repertoire of frontal gait disorders gives some indication of this complexity. For human walking, it is necessary to simultaneously achieve at least two tasks, such as maintaining a bipedal upright posture and locomotion. Particularly, postural control plays an extremely significant role in enabling the subject to maintain stable gait behaviors to adapt to the environment. To achieve these requirements, the frontal cortex (1) uses cognitive information from the parietal, temporal, and occipital cortices, (2) creates plans and programs of gait behaviors, and (3) acts on the brainstem and spinal cord, where the core posture-gait mechanisms exist. Moreover, the frontal cortex enables one to achieve a variety of gait patterns in response to environmental changes by switching gait patterns from automatic routine to intentionally controlled and learning the new paradigms of gait strategy via networks with the basal ganglia, cerebellum, and limbic structures. This chapter discusses the role of each area of the frontal cortex in behavioral control and attempts to explain how frontal lobe controls walking with special reference to postural control.

Relationships between changes in lateral vestibulospinal tract excitability and postural control by dynamic balance intervention in healthy individuals: A preliminary study.

Introduction: We conducted dynamic balance or static intervention on healthy young adults to examine the changes in lateral vestibulospinal tract (LVST) excitability and postural control that ensued following dynamic balance intervention and to investigate the correlation between these changes. Methods: Twenty-eight healthy young adults were randomly assigned to either the dynamic balance group or the control group. They performed either a dynamic balance or static intervention for 10 trials of 30 s each and were assessed for head jerks during the intervention to confirm adaptation to the intervention. The dynamic balance intervention consisted of maintaining balance on a horizontally unstable surface, whereas the control intervention involved standing in the same foot position as the dynamic balance intervention on a stable surface while completing a maze task. LVST excitability and postural stability were assessed before and after the interventions. LVST excitability was assessed as the change rate in the soleus H-reflex amplitude with galvanic vestibular stimulation (GVSH). The velocity and area of the center of pressure (COP) were examined in the eyes closed/foam rubber condition. Results: No significant main and interaction effects (task, time) were observed for GVSH and COP variables. In the dynamic balance intervention, head jerk significantly decreased, and GVSH-change and changes in head jerk and COP area were significantly negatively correlated. Discussion: The LVST excitability change for the dynamic balance intervention varied among the participants, although increased LVST excitability may have been related to increased postural stability.

Perinatal development of central vestibular neurons in mice.

Central circuitry of the vestibular nuclei integrates sensory inputs in the adaptive control of motor behaviors such as posture, locomotion, and gaze stabilization. Thus far, such circuits have been mostly examined at mature stages, whereas their emergence and early development have remained poorly described. Here, we focused on the perinatal period of murine development, from embryonic day E14.5 to post-natal day P5, to investigate the ontogeny of two functionally distinct vestibular neuronal groups, neurons projecting to the spinal cord via the lateral vestibulospinal tract (LVST) and commissural neurons of the medial vestibular nucleus that cross the midline to the contralateral nucleus. Using transgenic mice and retrograde labeling, we found that network-constitutive GABAergic and glycinergic neurons are already established in the two vestibular groups at embryonic stages. Although incapable of repetitive firing at E14.5, neurons of both groups can generate spike trains from E15.5 onward and diverge into previously established A or B subtypes according to the absence (A) or presence (B) of a two-stage spike after hyperpolarization. Investigation of several voltage-dependent membrane properties indicated that solely LVST neurons undergo significant maturational changes in their electrophysiological characteristics during perinatal development. The proportions of A vs B subtypes also evolve in both groups, with type A neurons remaining predominant at all stages, and type B commissural neurons appearing only post-natally. Together, our results indicate that vestibular neurons acquire their distinct morpho-functional identities after E14.5 and that the early maturation of membrane properties does not emerge uniformly in the different functional subpopulations of vestibulo-motor pathways.

A Neural Controller Model Considering the Vestibulospinal Tract in Human Postural Control.

Humans are able to control their posture in their daily lives. It is important to understand how this is achieved in order to understand the mechanisms that lead to impaired postural control in various diseases. The descending tracts play an important role in controlling posture, particularly the reticulospinal and the vestibulospinal tracts (VST), and there is evidence that the latter is impaired in various diseases. However, the contribution of the VST to human postural control remains unclear, despite extensive research using neuroscientific methods. One reason for this is that the neuroscientific approach limits our understanding of the relationship between an array of sensory information and the muscle outputs. This limitation can be addressed by carrying out studies using computational models, where it is possible to make and validate hypotheses about postural control. However, previous computational models have not considered the VST. In this study, we present a neural controller model that mimics the VST, which was constructed on the basis of physiological data. The computational model is composed of a musculoskeletal model and a neural controller model. The musculoskeletal model had 18 degrees of freedom and 94 muscles, including those of the neck related to the function of the VST. We used an optimization method to adjust the control parameters for different conditions of muscle tone and with/without the VST. We examined the postural sway for each condition. The validity of the neural controller model was evaluated by comparing the modeled postural control with (1) experimental results in human subjects, and (2) the results of a previous study that used a computational model. It was found that the pattern of results was similar for both. This therefore validated the neural controller model, and we could present the neural controller model that mimics the VST.

Reliability and laterality of the soleus H-reflex following galvanic vestibular stimulation in healthy individuals.

The vestibulospinal tract (VST) plays an important role in the control of the ipsilateral antigravity muscles, and the balance of left and right VST excitability is important in human postural control. A method for measuring VST excitability is the application of galvanic vestibular stimulation (GVS) before tibial nerve stimulation that evokes the soleus H-reflex; the change rate of the H-reflex amplitude is then evaluated. Assessments of VST excitability and the left and right balance could be useful when determining the pathology for interventions in postural control impairments. However, the reliability and laterality of this assessment have not been clarified, nor has its relationship to postural control. We investigated the reliability, laterality and standing postural control in relation to the degree of facilitation of the H-reflex following GVS in 15 healthy adults. The assessments were performed in two sessions, one each for the left- and right-sides, in random order. The inter-session reliability of the short-interval assessments of an increase in the H-reflex following GVS on both sides were sufficient. The degree of H-reflex facilitation by GVS showed no significant difference between the left- and right-sides in any session. There was a moderate positive correlation between the mediolateral position of the center of pressure in the eyes-closed standing on foam condition and the left/right ratio of the degree of increased H-reflex in the first-session. We concluded that this method for evaluating the increase in the soleus H-reflex following GVS has high inter-session reliability in the short-interval that did not differ between sides.

Posture influences on vestibulospinal tract excitability.

The human vestibulospinal tract has important roles in postural control, but it has been unknown whether vestibulospinal tract excitability is influenced by the body's postures. We investigated whether postures influence the vestibulospinal tract excitability by a neurophysiological method, i.e., applying galvanic vestibular stimulation (GVS) 100 ms before tibial nerve stimulation evoking the soleus H-reflex. GVS is a percutaneous stimulation, and it has not been clarified how the cutaneous input from GVS influences the facilitation effect of cathodal GVS on the soleus H-reflex amplitude. In Experiment 1, we evaluated the effects of GVS on the soleus H-reflex amplitude of subjects in the prone, supine, and sitting positions in random order to clarify the differences in the GVS effects among these postures. In Experiment 2, to determine whether the effects of GVS in the supine and sitting positions are due solely to cutaneous input from GVS, we provided GVS and cutaneous stimulations as conditioning stimuli and compared the effects in both postures. Interaction effects between postures and stimulus conditions were observed in both experiments. The facilitation rate of the maximum H-reflex amplitude by GVS in the sitting position was significantly higher than those in the prone and supine positions (Experiment 1). The facilitation rate of GVS was significantly larger than the cutaneous stimulation only in the sitting position (Experiment 2). These results indicate that vestibulospinal tract excitability may be higher in the sitting position than in either lying position (prone and supine), due mainly to the increased need for postural control.

Multimodal control of neck muscles for vestibular mediated head oscillation damping during walking: a pilot study.

PURPOSE: It is still in question whether head oscillation damping during walking forms a part of the vestibular function. The anatomical pathway from the vestibular system to the neck muscles via the medial vestibulospinal tract (MVST) is well known but there is a lack of knowledge of the exact influence and modulation of each other in daily life activities. METHODS: (I) We fixed a head-neck unit of a human cadaver specimen in a steal frame to determine the required pitch-torque for a horizontal head position. The mean value of the acquired pitch-torque was 0.54 Nm. (II) On a motorized treadmill we acquired kinematic data of the head, the sternum and both feet by wireless 3D IMUs for seven asymptomatic volunteers. Subsequently three randomized task conditions were performed. Condition 1 was walking without any irritation. Condition 2 imitated a sacculus irritation using a standardized cVEMP signal. The third condition used an electric neck muscle-irritation (TENS). The data were analyzed by the simulation environment software OpenSim 4.0. RESULTS: 8 neck muscle pairs were identified. By performing three different conditions we observed some highly significant deviations of the neck muscle peak torques. Analysing Euler angles, we found during walking a LARP and RALP head pendulum, which also was strongly perturbated. CONCLUSION: Particularly the pitch-down head oscillation damping is the most challenging one for neck muscles, especially under biomechanical concerns. Mainly via MVST motor activity of neck muscles  might be modulated by vestibular motor signals. Two simultaneous proprioceptor effects might optimize head oscillation damping. One might be a proprioceptive feedback loop to the vestibular nucleus. Another might trigger the cervicocollic reflex (CCR).

Lateral Medullary Syndrome Following Injury of Lateral Vestibulospinal Tract: Diffusion Tensor Imaging Study.

BACKGROUND: Unilateral lesions of vestibular nucleus can cause lateral medullary syndrome. Little is known about injury of medial and lateral vestibulospinal tract (VST) after dorsolateral medullary infarct. We investigated injury of the lateral VST in patients with typical central vestibular disorder using diffusion tensor tractography (DTT). METHODS: Seven patients with lateral medullary syndrome and ten control subjects were recruited. For the medial VST, we determined seed region of interest (ROI) as medial vestibular nuclei of pons and target ROI on posteromedial medulla. For the lateral VST, the seed ROI was placed on lateral vestibular nuclei of pons, and the target ROI on posterolateral medulla. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. RESULT: Reconstructed lateral VST on both sides had significantly lower FA values in patients than controls (p<0.05). Tract volume of lateral VST in affected side was significantly lower than unaffected side and control group (p<0.05). However, no DTI parameters of the medial VST differed between patients and controls (p>0.05). CONCLUSION: Injury of the lateral VST was demonstrated in patients with lateral vestibular syndrome following dorsolateral medullary infarct. Analysis of the lateral VST using DTT would be helpful in evaluation of patients with lateral medullary syndrome.

Effects of injuries to descending motor pathways on restoration of gait in patients with pontine hemorrhage.

BACKGROUND AND PURPOSE: Gait disturbance due to injuries of the descending motor pathway, including corticospinal tract (CST), corticoreticular pathway (CRP), and medial and lateral vestibulospinal tracts (VSTs), are commonly encountered disabling sequelae of pontine hemorrhage. We investigated relations between changes in the CST, CRP, and medial and lateral VST and corresponding changes in gait function in patients with pontine hemorrhage. METHOD: Nine consecutive stroke patients with pontine hemorrhage, and 6 age-matched normal subjects were recruited. Four patients were allocated to group A (can't walk independently) and 5 to group B (can walk independently). Diffusion tensor imaging (DTI) data were acquired twice at acute to subacute stage and chronic stage after stroke onset. Diffusion tensor tractography (DTT) was used to reconstruct CST, CRP, medial and lateral VST. RESULT: The CRP shows a significantly different between groups A and B in both initial and follow up DTT (p > 0.05). In contrast, CST, medial VST and lateral VST did not show a significant difference (p > 0.05). Regarding DTI parameters of CRPs in group A, percentages of patients with fractional anisotropy (FA) and mean diffusivity (MD) values more than two standard deviation from normal were higher by follow up DTI than by initial DTI, however, the CRPs in group B only showed increased abnormal range of MD. CONCLUSIONS: The CST does not play an essential role in recovery of independent walking and vestibulospinal tracts may not crucially affect recovery of independent walking in patients with pontine hemorrhage. In contrast, and intact CRP or changes of the CRP integrity appear to be related to the recovery of gait function.

Three Dimensional Identification of Medial and Lateral Vestibulospinal Tract in the Human Brain: A Diffusion Tensor Imaging Study.

Purpose: The vestibulospinal tract (VST) is involved in balance control and gait function. No research has identified the VST in the human brain. In the current study, we attempted to identify the medial and lateral VST in the human brain, using diffusion tensor tractography (DTT). Materials and Methods: We recruited 40 healthy volunteers for this study. For reconstruction of the medial VST, a seed region of interest (ROI) was placed on the medial vestibular nuclei in the pons and target ROI on the posteromedial medulla. For reconstruction of the lateral VST, a seed ROI was placed on the lateral vestibular nuclei of pons and the target ROI on the posterolateral medulla. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the medial and lateral VST were measured. Results: The medial VST, which originates from the medial vestibular nuclei, descends through the posteromedial medulla, and terminates at the anterior funiculus of the cervical spinal cord. The lateral VST originates from the lateral vestibular nuclei, and terminates in the anterior portion of lateral funiculus, through the posterolateral medulla. The FA value of medial VST was significantly higher than that of lateral VST. In contrast, the MD value and tract volume were significantly lower than those of lateral VST (p < 0.05). Conclusion: We identified the medial and lateral VST in the human brain using DTT and investigated the anatomical characteristics of the medial and lateral VST. The methodology and results of this study could be helpful to both clinicians and researchers in the neuroscience field.

Influence of Transcranial Direct Current Stimulation to the Cerebellum on Standing Posture Control.

Damage to the vestibular cerebellum results in dysfunctional standing posture control. Patients with cerebellum dysfunction have a larger sway in the center of gravity while standing compared with healthy subjects. Transcranial direct current stimulation (tDCS) is a noninvasive technique for selectively exciting or inhibiting specific neural structures with potential applications in functional assessment and treatment of neural disorders. However, the specific stimulation parameters for influencing postural control have not been assessed. In this study, we investigated the influence of tDCS when applied over the cerebellum on standing posture control. Sixteen healthy subjects received tDCS (20 min, 2 mA) over the scalp 2 cm below the inion. In Experiment 1, all 16 subjects received tDCS under three stimulus conditions, Sham, Cathodal, and Anodal, in a random order with the second electrode placed on the forehead. In Experiment 2, five subjects received cathodal stimulation only with the second electrode placed over the right buccinator muscle. Center of gravity sway was measured twice for 60 s before and after tDCS in a standing posture with eyes open and legs closed, and average total locus length, locus length per second, rectangular area, and enveloped area were calculated. In Experiment 1, total locus length and locus length per second decreased significantly after cathodal stimulation but not after anodal or sham stimulation, while no tDCS condition influenced rectangular or enveloped areas. In Experiment 2, cathodal tDCS again significantly reduced total locus length and locus length per second but not rectangular and enveloped areas. The effects of tDCS on postural control are polarity-dependent, likely reflecting the selective excitation or inhibition of cerebellar Purkinje cells. Cathodal tDCS to the cerebellum of healthy subjects can alter body sway (velocity).

Deiters' Nucleus. Its Role in Cerebellar Ideogenesis : The Ferdinando Rossi Memorial Lecture.

Otto Deiters (1834-1863) was a promising neuroscientist who, like Ferdinando Rossi, died too young. His notes and drawings were posthumously published by Max Schultze in the book "Untersuchungen über Gehirn und Rückenmark." The book is well-known for his dissections of nerve cells, showing the presence of multiple dendrites and a single axon. Deiters also made beautiful drawings of microscopical sections through the spinal cord and the brain stem, the latter showing the lateral vestibular nucleus which received his name. This nucleus, however, should be considered as a cerebellar nucleus because it receives Purkinje cell axons from the vermal B zone in its dorsal portion. Afferents from the labyrinth occur in its ventral part. The nucleus gives rise to the lateral vestibulospinal tract. The cerebellar B module of which Deiters' nucleus is the target nucleus was used in many innovative studies of the cerebellum on the zonal organization of the olivocerebellar projection, its somatotopical organization, its microzones, and its role in posture and movement that are the subject of this review.

Assessment of transmission in specific descending pathways in relation to gait and balance following spinal cord injury.

Human bipedal gait requires supraspinal control and gait is consequently severely impaired in most persons with spinal cord injury (SCI). Little is known of the contribution of lesion of specific descending pathways to the clinical manifestations of gait deficits. Here, we assessed transmission in descending pathways using imaging and electrophysiological techniques and correlated them with clinical measures of impaired gait in persons with SCI. Twenty-five persons with SCI participated in the study. Functional assessment of gait included the Walking Index for Spinal Cord Injury (WISCI), the Timed-Up and Go (TUG), the 6-Min Walking Test (6MWT), and the maximal treadmill gait speed. Balance was evaluated clinically by the Berg Balance Scale (BBS). The amplitude of tibialis anterior (TA) motor-evoked potentials (MEPs) at rest elicited by transcranial magnetic stimulation as a measure of corticospinal transmission showed a moderately good correlation with all clinical measures (r(2)~0.5), whereas the latency of the MEPs showed less good correlation (r(2)~0.35). Interestingly, the MEP amplitude was correlated to atrophy in the ventrolateral rather than the dorsolateral section of the spinal cord where the main part of the corticospinal tract is located. TA intramuscular coherence in the beta and gamma frequency range has been suggested to reflect corticospinal transmission and was, consistent with this, found to be correlated to atrophy in the dorsolateral and ventrolateral sections of the spinal cord. Coherence was found to correlate to all clinical measures to the same extent as the MEP amplitude. The latency and duration of medium-latency responses in the soleus muscle to galvanic stimulation as measures of vestibulospinal transmission showed very good correlation to BBS (r(2)=-0.8) and moderately good correlation to the assessments of gait function (r(2)~0.4). 6MWT and gait speed were correlated to atrophy of the lateral sections of the spinal cord bilaterally, whereas BBS was correlated to atrophy of both lateral and ventral sections of the spinal cord. No significant correlation was observed between the electrophysiological tests of corticospinal and vestibulospinal transmission. Combination of different electrophysiological and anatomical measures using best subset regression analysis revealed improved prediction of gait ability, especially in the case of WISCI. These findings illustrate that lesion of corticospinal and vestibulospinal pathways makes different contributions to impaired gait ability and balance following SCI and that no single electrophysiological or anatomical measure provide an optimal prediction of clinical gait and balance disability. We suggest using a combination of anatomical and electrophysiological measures when evaluating spinal cord integrity following SCI.

The effect of preterm birth on vestibular evoked myogenic potentials in children.

BACKGROUND: Preterm birth is a significant global health problem with serious short- and long-term consequences. This study examined the long term effects of preterm birth on vestibular evoked myogenic potentials (VEMPs) among preschool-aged children. METHODS: Thirty-one children with preterm and 20 children with term birth histories aged 5.5 to 6.5 years were studied. Each child underwent VEMPs testing using a 500 Hz tone-burst stimulus with a 95 dB nHL (normal hearing level) intensity level. RESULTS: The mean peak latencies of the p13 and n23 waves in the very preterm group were significantly longer than for the full-term group (p≤ 0.041). There was a significant difference between very and mildly preterm children in the latency of peak p13 (p= 0.003). No significant differences existed between groups for p13-n23 amplitude and the interaural amplitude difference ratio. The tested ear and gender did not affect the results of the test. CONCLUSION: Prolonged VEMPs in very preterm children may reflect neurodevelopmental impairment and incomplete maturity of the vestibulospinal tract (sacculocollic reflex pathway), especially myelination. VEMPs is a non-invasive technique for investigating the vestibular function in young children, and considered to be an appropriate tool for evaluating vestibular impairments at the low brainstem level. It can be used in follow-ups of the long-term effects of preterm birth on the vestibular system.

International guidelines for the clinical application of cervical vestibular evoked myogenic potentials: an expert consensus report.

BACKGROUND: Cervical vestibular evoked myogenic potentials (cVEMPs) are electromyogram responses evoked by high-level acoustic stimuli recorded from the tonically contracting sternocleidomastoid (SCM) muscle, and have been accepted as a measure of saccular and inferior vestibular nerve function. As more laboratories are publishing cVEMP data, there is a wider range of recording methods and interpretation, which may be confusing and limit comparisons across laboratories. OBJECTIVE: To recommend minimum requirements and guidelines for the recording and interpretation of cVEMPs in the clinic and for diagnostic purposes. MATERIAL AND METHODS: We have avoided proposing a single methodology, as clinical use of cVEMPs is evolving and questions still exist about its underlying physiology and its measurement. The development of guidelines by a panel of international experts may provide direction for accurate recording and interpretation. RESULTS: cVEMPs can be evoked using air-conducted (AC) sound or bone conducted (BC) vibration. The technical demands of galvanic stimulation have limited its application. For AC stimulation, the most effective frequencies are between 400 and 800 Hz below safe peak intensity levels (e.g. 140 dB peak SPL). The highpass filter should be between 5 and 30 Hz, the lowpass filter between 1000 and 3000 Hz, and the amplifier gain between 2500 and 5000. The number of sweeps averaged should be between 100 and 250 per run. Raw amplitude correction by the level of background SCM activity narrows the range of normal values. There are few publications in children with consistent results. CONCLUSION: The present recommendations outline basic terminology and standard methods. Because research is ongoing, new methodologies may be included in future guidelines.