Ataxia telangiectasia: a “disease model” to understand the cerebellar control of vestibular reflexes

2011 ◽  
Vol 105 (6) ◽  
pp. 3034-3041 ◽  
Author(s):  
Aasef G. Shaikh ◽  
Sarah Marti ◽  
Alexander A. Tarnutzer ◽  
Antonella Palla ◽  
Thomas O. Crawford ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Disease Model ◽  
Head Rotation ◽  
Vestibular Evoked Myogenic Potentials ◽  
Electromyographic Activity ◽  
Vestibular Reflexes ◽  
Healthy Humans ◽  
Motor Strategy ◽  
Eye Rotation ◽  
Cerebellar Cortical Degeneration

Experimental animal models have suggested that the modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulocerebellum and contribute to the control of gaze and balance. These critical vestibular functions have been infrequently quantified in human cerebellar disease. In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of several key vestibular reflexes. The vestibuloocular reflex (VOR) was measured by eye movement responses to changes in head rotation. The vestibulocollic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks led to electromyographic activity of the sternocleidomastoid muscle. The VOR gain (eye velocity/head velocity) was increased in all subjects with A-T. An increase of the VCR, paralleling that of the VOR, was indirectly suggested by an increase in cVEMP amplitude. In A-T subjects, alignment of the axis of eye rotation was not with that of head rotation. Subjects with A-T thus manifested VOR cross-coupling, abnormal eye movements directed along axes orthogonal to that of head rotation. Degeneration of the Purkinje neurons in the vestibulocerebellum probably underlie these deficits. This study offers insights into how the vestibulocerebellum functions in healthy humans. It may also be of value to the design of treatment trials as a surrogate biomarker of cerebellar function that does not require controlling for motivation or occult changes in motor strategy on the part of experimental subjects.

Dynamics of neck-to-forelimb reflexes in the decerebrate cat

1983 ◽  
Vol 50 (3) ◽  
pp. 688-695 ◽  
Author(s):  
K. Ezure ◽  
V. J. Wilson
Keyword(s):  
Head Rotation ◽  
Longitudinal Axis ◽  
Triceps Brachii ◽  
Vestibular Reflexes ◽  
Sinusoidal Analysis ◽  
Low Frequencies ◽  
Decerebrate Cat ◽  
Splenius Capitis ◽  
Response Phase ◽  
Stimulation Of

We have studied the neck-to-forelimb reflex evoked by head rotation around the longitudinal axis (roll) in the long and medial heads of triceps brachii of decerebrate, acutely labyrinthectomized cats. Reflexes were measured by recording mass electromyogram (EMG). As expected from the work of others, they were reciprocal in the two limbs, with excitation in the limb toward which the chin rotates. The reflex was sufficiently linear for a sinusoidal analysis. Although there was sometimes adaptation at stimulus frequencies of 0.1 Hz and below, response phase at these frequencies was usually in phase with position, and gain was flat. At higher frequencies there was some sensitivity to the velocity of the stimulus: gain increased with a slope of 10 dB/decade and phase advanced in some cats but not in others. Gain at low frequencies of head rotation, expressed as percent modulation of EMG, was typically 1%/deg or less. Reflexes evoked by head rotation in triceps and in the neck extensor splenius capitis have different dynamics. It remains to be determined whether this difference is due to activation of different receptors. We compared the dynamics of roll reflexes evoked by stimulation of neck receptors with those of vestibular reflexes evoked by tilt of the whole animal (23). Taking into account dynamics and gain, the two reflexes should cancel at low frequencies, as predicted by others. Above 0.2 Hz, cancellation becomes less effective.

scholarly journals Pain Induced during Both the Acquisition and Retention Phases of Locomotor Adaptation Does Not Interfere with Improvements in Motor Performance

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jason Bouffard ◽  
Laurent J. Bouyer ◽  
Jean-Sébastien Roy ◽  
Catherine Mercier
Keyword(s):  
Motor Performance ◽  
Temporal Distribution ◽  
Control Group ◽  
Electromyographic Activity ◽  
Locomotor Training ◽  
Locomotor Adaptation ◽  
Movement Error ◽  
Motor Strategy ◽  
Motor Strategies ◽  
Healthy Participants

Cutaneous pain experienced during locomotor training was previously reported to interfere with retention assessed in pain-free conditions. To determine whether this interference reflects consolidation deficits or a difficulty to transfer motor skills acquired in the presence of pain to a pain-free context, this study evaluated the effect of pain induced during both the acquisition and retention phases of locomotor learning. Healthy participants performed a locomotor adaptation task (robotized orthosis perturbing ankle movements during swing) on two consecutive days. Capsaicin cream was applied around participants’ ankle on both days for the Pain group, while the Control group was always pain-free. Changes in movement errors caused by the perturbation were measured to assess global motor performance; temporal distribution of errors and electromyographic activity were used to characterize motor strategies. Pain did not interfere with global performance during the acquisition or the retention phases but was associated with a shift in movement error center of gravity to later in the swing phase, suggesting a reduction in anticipatory strategy. Therefore, previously reported retention deficits could be explained by contextual changes between acquisition and retention tests. This difficulty in transferring skills from one context to another could be due to pain-related changes in motor strategy.

Extracting phase-dependent human vestibular reflexes during locomotion using both time and frequency correlation approaches

2011 ◽  
Vol 111 (5) ◽  
pp. 1484-1490 ◽  
Author(s):  
Jean-Sébastien Blouin ◽  
Christopher J. Dakin ◽  
Kees van den Doel ◽  
Romeo Chua ◽  
Bradford J. McFadyen ◽  
...  
Keyword(s):  
Vestibular Stimulation ◽  
Time Dependent ◽  
Medial Gastrocnemius ◽  
Electromyographic Activity ◽  
Step Cycle ◽  
Vestibular Reflexes ◽  
Time Frequency ◽  
Dynamic Modulation ◽  
Frequency Decomposition ◽  
Heel Contact

Daily activities, such as walking, may require dynamic modulation of vestibular input onto motoneurons. This dynamic modulation is difficult to identify in humans due to limitations in the delivery and analysis of current vestibular probes, such as galvanic vestibular stimulation. Stochastic vestibular stimulation, however, provides an alternative method to extract human vestibular reflexes. Here, we used time-dependent coherence and time-dependent cross-correlation, coupled with stochastic vestibular stimulation, to investigate the phase dependency of human vestibular reflexes during locomotion. We found that phase-dependent activity from the medial gastrocnemius muscles is correlated with the vestibular signals over the 2- to 20-Hz bandwidth during the stance phase of locomotion. Vestibular-gastrocnemius coherence and time-dependent cross-correlations reached maximums at 21 ± 4 and 23 ± 8% of the step cycle following heel contact and before the period of maximal electromyographic activity (38 ± 5%). These results demonstrate 1) the effectiveness of these techniques in extracting the phase-dependent modulation of vestibulomuscular coupling during a cyclic task; 2) that vestibulomuscular coupling is phasically modulated during locomotion; and 3) that the period of strongest vestibulomuscular coupling does not correspond to the period of maximal electromyographic activity in the gastrocnemius. Therefore, we have shown that stochastic vestibular stimulation, coupled with time-frequency decomposition, provides an effective tool to assess the contribution of vestibular ex-afference to the muscular control during locomotion.

Reflexive Limb Selection and Control of Reach Direction to Moving Targets in Cats, Monkeys, and Humans

2010 ◽  
Vol 104 (5) ◽  
pp. 2423-2432 ◽  
Author(s):  
Sergei Perfiliev ◽  
Tadashi Isa ◽  
Bo Johnels ◽  
Göran Steg ◽  
Johan Wessberg
Keyword(s):  
Target Position ◽  
Arm Movement ◽  
Parametric Programming ◽  
Visual Signal ◽  
Movement Direction ◽  
Electromyographic Activity ◽  
Motor Strategy ◽  
Limb Selection ◽  
The Right ◽  
And Control

When we reach for an object, we have to decide which arm to use and the direction in which to move. According to the established view, this is voluntarily controlled and programmed in advance in time-consuming and elaborate computations. Here, we systematically tested the motor strategy used by cats, monkeys, and humans when catching an object moving at high velocity to the left or right. In all species, targets moving to the right selectively initiated movement of the right forelimb and vice versa for targets moving to the left. Movements were from the start directed toward a prospective target position. In humans, the earliest onset of electromyographic activity from start of motion of the target ranged from 90 to 110 ms in different subjects. This indicates that the selection of the arm and specification of movement direction did not result from the subject's voluntary decision, but were determined in a reflex-like manner by the parameters of the target motion. As a whole the data suggest that control of goal-directed arm movement relies largely on an innate neuronal network that, when activated by the visual signal from the target, automatically guides the arm throughout the entire movement toward the target. In the view of the present data, parametric programming of reaching in advance seems to be superfluous.

Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. I. Responses in normal subjects

1996 ◽  
Vol 76 (6) ◽  
pp. 4009-4020 ◽  
Author(s):  
S. T. Aw ◽  
T. Haslwanter ◽  
G. M. Halmagyi ◽  
I. S. Curthoys ◽  
R. A. Yavor ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Rotation Axis ◽  
Three Dimensional ◽  
Head Rotation ◽  
Normal Subjects ◽  
Three Dimensions ◽  
Head Velocity ◽  
Velocity Magnitude ◽  
High Acceleration ◽  
Eye Rotation

1. The kinematics of the human angular vestibuloocular reflex (VOR) in three dimensions was investigated in 12 normal subjects during high-acceleration head rotations (head “impulses”). A head impulse is a passive, unpredictable, high-acceleration (3,000–4,000 degrees/s2) head rotation of approximately 10–20 degrees in roll, pitch, or yaw, delivered with the subject in the upright position and focusing on a fixation target. Head and eye rotations were measured with dual search coils and expressed as rotation vectors. The first of these two papers describes a vector analysis of the three-dimensional input-output kinematics of the VOR as two indexes in the time domain: magnitude and direction. 2. Magnitude is expressed as speed gain (G) and direction as misalignment angle (delta). G is defined as the ratio of eye velocity magnitude (eye speed) to head velocity magnitude (head speed). delta is defined as the instantaneous angle by which the eye rotation axis deviates from perfect alignment with the head rotation axis in three dimensions. When the eye rotation axis aligns perfectly with the head rotation axis and when eye velocity is in a direction opposite to head velocity, delta = 0. The orientation of misalignment between the head and the eye rotation axes is characterized by two spatial misalignment angles, which are the projections of delta onto two orthogonal coordinate planes that intersect at the head rotation axis. 3. Time series of G were calculated for head impulses in roll, pitch, and yaw. At 80 ms after the onset of an impulse (i.e., near peak head velocity), values of G were 0.72 +/- 0.07 (counterclockwise) and 0.75 +/- 0.07 (clockwise) for roll impulses, 0.97 +/- 0.05 (up) and 1.10 +/- 0.09 (down) for pitch impulses, and 0.95 +/- 0.06 (right) and 1.01 +/- 0.07 (left) for yaw impulses (mean +/- 95% confidence intervals). 4. The eye rotation axis was well aligned with head rotation axis during roll, pitch, and yaw impulses: delta remained almost constant at approximately 5–10 degrees, so that the spatial misalignment angles were < or = 5 degrees. delta was 9.6 +/- 3.1 (counterclockwise) and 9.0 +/- 2.6 (clockwise) for roll impulses, 5.7 +/- 1.6 (up) and 6.1 +/- 1.9 (down) for pitch impulses, and 6.2 +/- 2.2 (right) and 7.9 +/- 1.5 (left) for yaw impulses (mean +/- 95% confidence intervals). 5. VOR gain (gamma) is the product of G and cos(delta). Because delta is small in normal subjects, gamma is not significantly different from G. At 80 ms after the onset of an impulse, gamma was 0.70 +/- 0.08 (counterclockwise) and 0.74 +/- 0.07 (clockwise) for roll impulses, 0.97 +/- 0.05 (up) and 1.09 +/- 0.09 (down) for pitch impulses, and 0.94 +/- 0.06 (right) and 1.00 +/- 0.07 (left) for yaw impulses (mean +/- 95% confidence intervals). 6. VOR latencies, estimated with a latency shift method, were 10.3 +/- 1.9 (SD) ms for roll impulses, 7.6 +/- 2.8 (SD) ms for pitch impulses, and 7.5 +/- 2.9 (SD) ms for yaw impulses. 7. We conclude that the normal VOR produces eye rotations that are almost perfectly compensatory in direction as well as in speed, but only during yaw and pitch impulses. During roll impulses, eye rotations are well aligned in direction, but are approximately 30% slower in speed.

Kinematics of the Rotational Vestibuloocular Reflex: Role of the Cerebellum

2007 ◽  
Vol 98 (1) ◽  
pp. 295-302 ◽  
Author(s):  
Mark F. Walker ◽  
Jing Tian ◽  
David S. Zee
Keyword(s):  
Tilt Angle ◽  
Three Dimensional ◽  
Head Rotation ◽  
Normal Subjects ◽  
Eye Position ◽  
Vestibuloocular Reflex ◽  
Gaze Stabilization ◽  
Eye Rotation ◽  
Axis Rotation ◽  
Head Impulses

We studied the effect of cerebellar lesions on the 3-D control of the rotational vestibuloocular reflex (RVOR) to abrupt yaw-axis head rotation. Using search coils, three-dimensional (3-D) eye movements were recorded from nine patients with cerebellar disease and seven normal subjects during brief chair rotations (200°/s2 to 40°/s) and manual head impulses. We determined the amount of eye-position dependent torsion during yaw-axis rotation by calculating the torsional-horizontal eye-velocity axis for each of three vertical eye positions (0°, ±15°) and performing a linear regression to determine the relationship of the 3-D velocity axis to vertical eye position. The slope of this regression is the tilt angle slope. Overall, cerebellar patients showed a clear increase in the tilt angle slope for both chair rotations and head impulses. For chair rotations, the effect was not seen at the onset of head rotation when both patients and normal subjects had nearly head-fixed responses (no eye-position-dependent torsion). Over time, however, both groups showed an increasing tilt-angle slope but to a much greater degree in cerebellar patients. Two important conclusions emerge from these findings: the axis of eye rotation at the onset of head rotation is set to a value close to head-fixed (i.e., optimal for gaze stabilization during head rotation), independent of the cerebellum and once the head rotation is in progress, the cerebellum plays a crucial role in keeping the axis of eye rotation about halfway between head-fixed and that required for Listing's Law to be obeyed.

scholarly journals A patient-derived olfactory stem cell disease model for ataxia-telangiectasia

2013 ◽  
Vol 22 (12) ◽  
pp. 2495-2509 ◽  
Author(s):  
Romal Stewart ◽  
Sergei Kozlov ◽  
Nicholas Matigian ◽  
Gautam Wali ◽  
Magtouf Gatei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ataxia Telangiectasia ◽  
Disease Model ◽  
Cell Disease

scholarly journals Exercise-induced abdominal muscle fatigue in healthy humans

2006 ◽  
Vol 100 (5) ◽  
pp. 1554-1562 ◽  
Author(s):  
Bryan J. Taylor ◽  
Stephen C. How ◽  
Lee M. Romer
Keyword(s):  
Peak Oxygen Uptake ◽  
Abdominal Muscle ◽  
Rectus Abdominis ◽  
Voluntary Activation ◽  
Abdominal Muscles ◽  
Electromyographic Activity ◽  
Membrane Excitability ◽  
Healthy Humans ◽  
Gastric Pressure ◽  
Exercise Induced

The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (V̇o2 peak) = 50.0 ± 1.9 (SE) ml·kg−1·min−1] cycled at >90% V̇o2 peak to exhaustion (14.2 ± 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1–25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean −25 ± 4%; P < 0.001) that persisted up to 30 min postexercise (−12 ± 4%; P = 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 ± 13 before vs. 145 ± 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 ± 6 before vs. 64 ± 2% after exercise; P = 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms.

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