Voluntary suppression of neck reflexes during passive head-on-trunk rotations: reflex gain control versus proprioceptive feedback.

Normal subjects can completely eliminate resistance upon imposed head-on-trunk rotations when they are asked to relax. It is not, however, clear how neck reflexes to stretch can be voluntarily suppressed. Reflexive responses might be modified by adjusting the gain of the reflex loop through descending control. Theoretically, necessary corrections upon interfering disturbances during coordinated motor performance requiring the interplay of relaxation/activation may be missing if muscle relaxation is taking place exclusively by this mechanism. It has been alternatively proposed that sensory information from the periphery may be allowed to "neutralize" neck reflexes if it is fed back with opposite sign to the structures driving the reflexes. Six healthy subjects were asked to relax while subjected to head-on-trunk rotations generated by a head motor. After any initial resistance had completely subsided, the head was unexpectedly exposed to "ramp-and-hold" perturbations of up to 2° amplitude and 0.7 s duration. Resistance to stretch consistently reappeared thereupon, suggesting that stretch reflex gain had not been set to zero during the previously achieved complete relaxation. Resistance to perturbations under these circumstances was compared with the forces generated when the same ramp-and-hold displacements were delivered unpredictably to the head held stationary. A quantitative model of neck proprioceptive reflexes suppression has been thus constructed. Gain scheduling or "motor set" cannot sufficiently account for the voluntary reflex suppression during slow passive head rotations. Instead, we propose as underlying mechanism, the "neutralization" of the controlling servo by means of continuous feedback tracking displacement and force signals from the periphery.NEW & NOTEWORTHY Head stabilizing neck reflexes can be voluntarily suppressed or activated depending on the task at hand. By applying brief perturbations unexpectedly, both during passive head-on-trunk movements and at rest, we investigated the mechanism of voluntary suppression of resistance to stretch. A physiologically plausible, neuromechanical model of voluntary/reflexive interactions was constructed favoring feedback over reflex gain adjustments. Accordingly, muscle relaxation during imposed head movements is based on sensory feedback similarly to muscle contractions during purposeful movements.

Large gaze shift generation while standing: the role of the vestibular system.

The functional significance of vestibular information for the generation of gaze shifts is controversial and less well established than the vestibular contribution to gaze stability. In this study, we asked seven bilaterally avestibular patients to execute voluntary, whole body pivot turns to visual targets up to 180° while standing. In these conditions, not only are the demands imposed on gaze transfer mechanisms more challenging, but also neck proprioceptive input represents an inadequate source of head-in-space motion information. Patients' body segment was slower and jerky. In the absence of visual feedback, gaze advanced in small steps, closely resembling normal multiple-step gaze-shift patterns, but as a consequence of the slow head motion, target acquisition was delayed. In ~25% of trials, however, patients moved faster but the velocity of prematurely emerging slow-phase compensatory eye movements remained lower than head-in-space velocity due to vestibuloocular failure. During these trials, therefore, gaze advanced toward the target without interruption but, again, taking longer than when normal controls use single-step gaze transfers. That is, even when patients attempted faster gaze shifts, exposing themselves to gaze instability, they acquired distant targets significantly later than controls. Thus, while patients are upright, loss of vestibular information disrupts not only gaze stability but also gaze transfers. The slow and ataxic head and trunk movements introduce significant foveation delays. These deficits explain patients' symptoms during upright activities and show, for the first time, the clinical significance of losing the so-called "anticompensatory" (gaze shifting) function of the vestibuloocular reflex.NEW & NOTEWORTHY Previous studies in sitting avestibular patients concluded that gaze transfers are not substantially compromised. Still, clinicians know that patients are impeded (e.g., looking side to side before crossing a road). We show that during large gaze transfers while standing, vestibularly derived head velocity signals are critical for the mechanisms governing reorientation to distant targets and multisegmental coordination. Our findings go beyond the traditional role of the vestibular system in gaze stability, extending it to gaze transfers, as well.

Idiothetic signal processing and spatial orientation in patients with unilateral hippocampal sclerosis.

The role of the hippocampus in spatial navigation and the presence of vestibular-responsive neurons in limbic areas are well-established from animal experiments. However, hippocampal spatial processing in humans is not fully understood. Here, we employed real whole body and head-on-trunk rotations to investigate how vestibular signals, either alone or in combination with neck-proprioceptive stimulation, shape the spatial frame of reference in patients with unilateral hippocampal sclerosis (HS). Patients were asked to point in darkness with a light spot, moved on a cylindrical screen by means of a joystick, into their visual straight-ahead direction (VSA), to remember this direction in space, and to revert back to this point after the rotations. Estimates in patients with HS were compared with those of healthy controls and of patients with epilepsy without hippocampal involvement. All groups produced similar errors after low-frequency vestibular stimuli. These errors were eliminated when rotations involved concurrent neck stimulation. Significantly increased variability was observed, however, in both the VSA and reposition estimates after the rotations in patients with HS compared with controls. These results suggest that cognitive processing of idiothetic signals for self-motion perception is inaccurate in patients with HS. Importantly, however, the responses of patients with HS showed no spatial lateralization with regard to right or left HS, suggesting that the underlying neuronal loss attenuates the precision of head-direction signal decoding in a nondirectional manner. Hence, patients are unable to use these signals as efficiently as normal subjects in the construction of a stable head-centric spatial frame of reference. NEW & NOTEWORTHY Spatial perception relies on combined processing of various idiothetic (vestibular and proprioceptive) and allothetic (visual and auditory) sensory signals. Despite the established knowledge of rodent vestibular-hippocampal interactions, human data are lacking. We investigated idiothetic orientational processing in subjects with unilateral hippocampal sclerosis using various combinations of vestibular and proprioceptive stimuli. Hippocampal impairment leads to less accurate, noisy decoding of the signal related to idiothetic orientation. However, patients did not show any lateralized deficits of visual straight-ahead perception or of target/self-displacement perception after idiothetic stimulation.

Fast gaze reorientations by combined movements of the eye, head, trunk and lower extremities.

Large reorientations of the line of sight, involving combined rotations of the eyes, head, trunk and lower extremities, are executed either as fast single-step or as slow multiple-step gaze transfers. In order to obtain more insight into the mechanisms of gaze and multisegmental movement control, we have investigated time-optimal gaze shifts (i.e. with the instruction to move as fast as possible) during voluntary whole-body rotations to remembered targets up to 180° eccentricity performed by standing healthy humans in darkness. Fast, accurate, single-step movement patterns occurred in approximately 70 % of trials, i.e. considerably more frequently than in previous studies with the instruction to turn at freely chosen speed (30 %). Head-in-space velocity in these cases was significantly higher than during multiple-step transfers and displayed a conspicuously regular bell-shaped profile, increasing smoothly to a peak and then decreasing slowly until realignment with the target. Head-in-space acceleration was on average not different during reorientations to the different target eccentricities. In contrast, head-in-space velocity increased with target eccentricity due to the longer duration of the acceleration phase implemented during trials to more distant targets. Eye saccade amplitude approached the eye-in-orbit mechanical limit and was unrelated to eye/head velocity, duration or target eccentricity. Overall, the combined movement was stereotyped such that the first two principal components accounted for data variance almost up to gaze shift end, suggesting that the three mechanical degrees of freedom under consideration (eye-in-orbit, head-on-trunk and trunk-in-space) are on average reduced to two kinematic degrees of freedom (i.e. eye, head-in-space). Synchronous EMG activity in the anterior tibial and gastrocnemius muscles preceded the onset of eye rotation. Since the magnitude and timing of peak head-in-space velocity were scaled with target eccentricity and because head-on-trunk and trunk-in-space displacements were on average linearly correlated, we propose a separate controller for head-in-space movement, whereas the movement of the eye-in-space may be, in contrast, governed by global, i.e. gaze feedback. The rapid progression of the line of sight can be sustained, and the reactivation of the vestibulo-ocular reflex would be postponed, until gaze error approaches zero only in association with a strong head-in-space neural control signal.

Altered eye-to-foot coordination in standing parkinsonian patients during large gaze and whole-body reorientations.

We investigated whether turning problems in Parkinson's disease may be the result of abnormal horizontal multisegmental angular coordination. Ten mildly affected patients and controls stood upright and voluntarily reoriented eyes and body to illuminated targets of eccentricities up to ±180 degrees. The effects of target location, visibility, and predictability on movement parameters were evaluated. Patients' latencies were normal. Control subjects foveated large eccentricity targets with a single gaze shift in approximately 30% of predictable trials. Patients rarely did so (10% of predictable trials) because of reduced head-in-space and trunk velocity. This resulted in massive foveation delays in patients-an average of half a second for displacements of 180 degrees. The covariation of eye, head, and trunk rotations was quantified statistically by means of principal components analysis. In both groups, the combined movement was initially stereotyped and two principal components accounted for nearly all data variance-the original three mechanical degrees of freedom (i.e., eye-head-trunk) are reduced to two kinematic degrees of freedom. However, in patients, the eye contributed more, and the head and trunk less, to the gaze shift than in control subjects. Although the eye-to-foot turning synergy is preserved in early-stage parkinsonism, quantitative differences are prominent, particularly a larger ocular (and smaller head-trunk) contribution in patients. Turning problems in Parkinson's disease do not result from inability to assemble multisegmental movements, as patients' ability to control numerous degrees of freedom is preserved. However, trunk bradykinesia reduces the frequency of single-step gaze shifts, thus prolonging target acquisition time. Preserved eye motion compensates for trunk slowness.

Is plasma calcium concentration implicated in the development of critical illness polyneuropathy and myopathy?

INTRODUCTION: This prospective study investigated whether plasma ionized calcium concentration abnormalities and other electrolyte disturbances represent risk factors for the development of critical illness polyneuromyopathy (CIPNM) in ICU patients. METHODS: One hundred and ninety consecutive adult critically ill patients with prolonged ICU stay (longer than 7 days) were prospectively evaluated. Patients with acute weakness and/or weaning difficulties were subjected to extensive electrophysiological measurements in order to establish the diagnosis of CIPNM. All recognized and/or possible risk factors for development of CIPNM were recorded. RESULTS: The diagnosis of CIPNM was confirmed in 40 patients (21.05%). By applying a logistic regression model, hypocalcemia (P = 0.02), hypercalcemia (P = 0.01) and septic shock (P = 0.04) were independently associated with the development of CIPNM in critically ill patients. CONCLUSIONS: We found that septic shock and abnormal fluctuations of plasma Ca²âº concentration represent significant risk factors for the development of CIPNM in critically ill patients.

Kinematic redundancy and variance of eye, head and trunk displacements during large horizontal gaze reorientations in standing humans.

Shifting the direction of the line of sight in everyday life often involves rotations not only of the eyes and head but also of the trunk. Here, we investigated covariation patterns of eye-in-orbit, head-on-trunk and trunk-in-space angular horizontal displacements during whole-body rotations to targets of up to 180 degrees eccentricity performed by standing healthy human subjects. The spatial covariation was quantified statistically across various behavioral task conditions (unpredictable, memory driven predictable, visual feedback) and constraints (accuracy) by principal components (PC) analysis. Overall, the combined movement was stereotyped such that the first two PCs accounted for essentially the whole data variance of combined gaze transfers up to about 400 ms, suggesting that the three mechanical degrees of freedom under consideration are reduced to two kinematic degrees of freedom. Moreover, quantification of segment velocity variability across repetitions showed that velocities of eye-in-space and head-in-space (i.e. 'end-point' velocity) were less variable than those of the elemental variables composing them. In contrast, three statistically significant PCs accounted for the covariation of the three segments during presumably vestibularly mediated nystagmic transfers, suggesting control by a separate driving circuit. We conclude that progression of the line of sight is initially stereotypic and fulfills criteria defining a motor synergy.

Tremor in Parkinson's Disease May Arise from Interactions of Central Rhythms with Spinal Reflex Loop Oscillations.

It is commonly believed that tremor, one of the cardinal signs of Parkinson's disease, is associated with cerebello-thalamo-cortical oscillations set off by the dopamine-depleted basal ganglia networks. The triggering mechanism has been, however, not entirely delineated. Several reports have pointed to the relevance of interactions with peripheral/spinal mechanisms to tremor generation. Investigations of motor unit synchronization and discharge patterns suggested that exaggerated beta-band oscillations may intermittently reach alpha-motoneurons and modulate low-amplitude membrane oscillations due to spinal loop transmission delays. As a result, the spinal reflex loop will oscillate more vigorously and at a lower frequency and, in turn, entrain larger transcortical loops. Motoneurons may thus represent the specific generator "node" in a tremor network encompassing both cerebral and peripheral/spinal recurrent circuits.

Gaze displacement and inter-segmental coordination during large whole body voluntary rotations.

Displacements of the visual axis and multi-segmental (eye-to-foot) coordination in the yaw plane were studied in ten human subjects (Ss) during voluntary reorientations to illuminated targets of eccentricities up to 180 degrees . We also investigated how knowledge of target location modifies the movement pattern. Eccentric targets (outbound trials) elicited eye, head, trunk and foot movements at latencies ca. 0.5, 0.6, 0.7 and 1.1 s, respectively. Knowledge of target location (return trials) reduced latencies for foot and trunk (but not eye and head) thus eye, head and trunk moved more en bloc. In most trials, the initial gaze shift fell short of the target and more than 50% of the visual angle was covered by the sum of vestibular nystagmic fast phases and head-in-space displacement, until target fixation. This indicates that during large gaze shifts the 'anticompensatory' role of the vestibulo-ocular reflex in target acquisition is prominent. During some predictable trials Ss acquired targets with a single large gaze shift, shortening target acquisition time by more than 200 ms. In these, gaze velocity (trunk-in-space + head-on-trunk + eye-in-orbit) remained often fairly constant for durations of up to 500 ms, suggesting that gaze velocity is a controlled parameter. Such pattern occurred during trunk mobilization, thus eye velocity co-varied with head-in-space rather than head-on-trunk velocity. Foot rotations were stereotyped and of constant frequency, suggesting they are generated by locomotor pattern generators. However, knowledge of target location reduced foot latencies indicating that local and supraspinal mechanisms interact for foot control. We propose that a single controller is responsible for the coupling of the multiple body segments and gaze velocity control during gaze shifts.

Square-wave jerks and smooth pursuit impairment as subtle early signs of brain involvement in Langerhans' cell histiocytosis.

Central nervous system (CNS) involvement in Langerhans' cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by motor and cognitive decline. Detailed analysis of ocular motor abnormalities is lacking. We report on a 60-year-old male with histologically confirmed LCH who developed oscillopsia and gait ataxia over a 1-year period. Eye movements recorded with infrared oculography revealed a high rate of square-wave jerks (SWJ) with frequencies of 41 min(-1) on average and amplitudes between 1 degrees and 7 degrees , as well as marked impairment of smooth tracking of sinusoidally moving targets. Furthermore, static posturography disclosed increased body sway, with an abnormally high sway path. The initial brain MRI was unremarkable. Due to the presumed cerebellar dysfunction we performed a second MRI 1 year later that disclosed deep cerebellar lesions compatible with LCH relapse within the CNS. The abnormal high SWJ rate and the impaired smooth pursuit performance correctly heralded later involvement of the cerebellum anticipating lesion appearance in the MRI.

Idiopathic spasmodic torticollis is not associated with abnormal kinesthetic perception from neck proprioceptive and vestibular afferences.

Proceeding from recent evidence for a sensory involvement in the pathophysiology of idiopathic spasmodic torticollis (ST), we asked whether the abnormal head posture of these patients is associated with distortions of their internal spatial reference frames due to abnormal processing of neck proprioceptive and/or vestibular input. Twelve ST patients were instructed to estimate, by adjusting a light pointer in the dark, their head and trunk mid-sagittal directions (as representatives of ego-centric references) and to reproduce a remembered target location in space (space centric reference). They did so before and after horizontal head and trunk rotations, which evoked isolated or combined vestibular and/or neck stimulation. In ST patients, unlike in normal controls, pre-stimulus estimates of the head and trunk mid-sagittal directions (baselines) showed a pronounced across-subjects variability, with essentially normal mean values. Their post-stimulus estimates in all tasks, after correction for the individual baseline errors, were normal with respect to both amplitude and variability, independent of stimulus direction, modality and rotation dynamics. Our findings suggest that ST patients have a rather inaccurate knowledge of their head posture, but can effectively use neck proprioceptive input and vestibular cues when estimating head and trunk displacements in ego-centric and space centric spatial orientation tasks. We propose that an offset of a non-sensory set point signal in the neck proprioceptive loop for head-on-trunk control may be responsible for the pathological head deviation in ST.

Interactions between voluntary head control and neck proprioceptive reflexes in cervical dystonia.

BACKGROUND: To investigate deficiencies in mechanisms of sensorimotor processing and reflexive-voluntary interactions leading to the impaired head position control in primary cervical dystonia. METHODS: Thirteen patients and 23 healthy controls were subjected to transient, low amplitude, low velocity head-on-trunk, trunk-under-head and whole-body rotations in the horizontal plane. With the instruction not to resist the imposed displacements, resistance to horizontal neck deflections was evaluated. RESULTS: Patients exhibited a torque offset (bias) in the direction of torticollis before stimulus application. While controls reduced and occasionally eliminated completely the initial resistance to head-to-trunk rotations, torque in patients increased throughout displacements. Change of resistance relative to baseline in patients was, however, symmetrical, i.e. independent of torticollis direction. Spontaneous torque fluctuations were significantly larger in patients. Strong correlations existed among these abnormal findings. CONCLUSIONS: Patients' ability to manipulate normal postural reactions to head-trunk rotations is impaired. The deficit is bilateral and correlates with the degree of abnormal posture. The present study extends previous work on reflexive-voluntary interactions and provides evidence that malfunctioning proprioceptive feedback may contribute to the pathophysiology of cervical dystonia.

Trunk bradykinesia and foveation delays during whole-body turns in spasmodic torticollis.

We have investigated how the abnormal head posture and motility in spasmodic torticollis interferes with ecological movements such as combined eye-to-foot whole-body reorientations to visual targets. Eight mildly affected patients and 10 controls voluntarily rotated eyes and body in response to illuminated targets of eccentricities up to ± 180°. The experimental protocol allowed separate evaluation of the effects of target location, visibility and predictability on movement parameters. Patients' latencies of eye, head, trunk and foot motion were prolonged but showed a normal modification pattern when target location was predictable. Peak head-on-trunk displacement and velocity were reduced both ipsi- and contralaterally with respect to the direction of torticollis. Surprisingly, peak trunk velocity was also reduced, even more than in previously studied patients with Parkinson's disease. As a consequence, patients made short, hypometric gaze saccades and only exceptionally foveated initially nonvisible targets with a single large gaze shift (4 % of predictable trials as opposed to 30 % in controls). Foveation of distant targets was massively delayed by more than half a second on average. Spontaneous dystonic head movements did not interfere with the execution of voluntary gaze shifts. The results show that neck dystonia does not arise from gaze (head-eye) motor centres but the eye-to-foot turning synergy is seriously compromised. For the first time we identify significant 'secondary' complications of torticollis such as trunk bradykinesia and foveation delays, likely to cause additional disability in patients. Eye movements per se are intact and compensate for the reduced head/trunk performance in an adaptive manner.

Invariance of vestibulo-ocular reflex gain to head impulses in pitch at different initial eye-in-orbit elevations: implications for Alexander's law.

CONCLUSIONS: These findings are in line with previous data on the horizontal vestibulo-ocular reflex (VOR) from this laboratory and suggest that eye position signals do not modulate natural vestibular responses. Hence, the Alexander's law (AL) phenomenon cannot be interpreted simply as a consequence of vestibular or oculomotor nuclei activity modulation with desired gaze. BACKGROUND: AL states that the intensity of the spontaneous nystagmus of a patient with a unilateral vestibular lesion grows with increasing gaze in the direction of the fast phase. Some of the mechanisms proposed to account for the gaze effects assume a direct modification of the normal VOR by eye position signals. We tested the validity of these assumptions and investigated the effects of gaze direction on the normal vertical human VOR in the behaviorally relevant high frequency range. METHODS: Head and eye movements were recorded with the search coil method during passive head impulses in pitch, while subjects were asked to hold gaze at various elevation angles in 8° steps within ± 16° from the straight ahead reference position. RESULTS: Upward and downward head rotations produced VOR gains of similar magnitude. Furthermore, the gain remained unaffected by eye-in-orbit position for both upward and downward head impulses.

Single-plane compensatory phase shift of head and eye oscillations in infantile nystagmus syndrome.

A 43-year-old man with infantile nystagmus syndrome complained of "head tremor" that would occur during attempted reading. Three-dimensional, combined eye and head recordings were performed with the magnetic search coil technique in two conditions: 1) looking straight-ahead under photopic conditions without a particular attentional focus and 2) reading a simple text held one meter away. A mainly vertical-horizontal spontaneous nystagmus was evident in both conditions, whereas head nodding emerged in the second condition. The head oscillated only in the vertical plane and concomitant analysis of eye and head displacement revealed a counterphase, compensatory pattern of the first harmonic of the INS waveform. This was verified by the significant negative peak of the crosscorrelogram at zero lag. Eye-in-space (gaze) displacement during nystagmic oscillations was thereby reduced suggesting a central adaptive behavior that may have evolved to partly compensate for the abnormal eye movements during reading.

Alexander's law during high-acceleration head rotations in humans.

Alexander's law states that the amplitude of the spontaneous nystagmus grows with increasing gaze in the direction of the fast phase. Using the search-coil method we employed head impulses at various eye-in-orbit azimuth angles to test (i) whether the normal vestibulo-ocular reflex (VOR) in the behaviorally relevant high-frequency range has intrinsic properties that could account for Alexander's law and (ii) whether such properties can also be shown in patients with unilateral vestibulopathy. We showed that the gain of the VOR remained unaffected by eye-in-orbit position in contols and in patients, both on ipsilesional and contralesional stimuli. These findings suggest that eye-in-orbit position does not directly modulate the activity in VOR pathways, neither during unbalanced but reciprocal (in controls), nor during unbalanced and nonreciprocal natural vestibular stimulation (in patients).

Neck rigidity in Parkinson's disease patients is related to incomplete suppression of reflexive head stabilization.

Muscle rigidity in PD (Parkinson's disease) patients represents an involuntary increase in muscle tone that stands out upon passive rotation of a joint. The pathophysiology of rigidity is still not well understood. We measured head-trunk torque in PD patients and normal controls during transient passive head rotations by means of servomotors under the instruction to the subjects to relax the neck muscles. We observed that rotation onset was followed by an initial rapid rise in resistive torque, similarly in both subject groups. It then leveled off or declined in controls. With PD patients, in contrast, the rise continued roughly proportional to head eccentricity almost until the end of the rotation. These observations led us to the hypothesis that the initial rise in torque represents reflexive head stabilization that normal subjects in the course of the rotational stimulus are able to suppress, whereas PD patients are less effective in doing so. The hypothesis was implemented into a dynamic control model of active and passive head rotation. Model simulations successfully reproduced the torque responses of normal subjects and PD patients in the present and previous studies.