Experimental Brain Research

Arata, Akiko; Onimaru, H.; Homma, Ikuo

doi: 10.1007/s002210050355pmid: 9588774

We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED 50 =0.5 μM) on the respiratory rhythm was stronger than NA (ED 50 =5 μM). The adrenaline respiratory rhythm depression was partially blocked by the α 1 -antagonist prazosin or by the α 2 -antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the α 1 -antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited ( n =29 of 39) or depressed ( n =5 of 39) by adrenaline, and excited by α 1 -agonist phenylephrine or depressed by α 2 -agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA A -antagonists bicuculline or picrotoxin, but not by the GABA B -antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through α-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via α 1 -receptors and inhibition via α 2 -receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA A ergic neurons.

Freitag, P.; Greenlee, M. W.; Lacina, T.; Scheffler, K.; Radü, E. W.

doi: 10.1007/s002210050356pmid: 9588775

We have studied the effects of pursuit eye movements on the functional magnetic resonance imaging (fMRI) responses in extrastriate visual areas during visual motion perception. Echoplanar imaging of 10–12 image planes through visual cortex was acquired in nine subjects while they viewed sequences of random-dot motion. Images obtained during stimulation periods were compared with baseline images, where subjects viewed a blank field. In a subsidiary experiment, responses to moving dots, viewed under conditions of fixation or pursuit, were compared with those evoked by static dots. Eye movements were recorded with MR-compatible electro-oculographic (EOG) electrodes. Our findings show an enhanced level of activation (as indexed by blood-oxygen level-dependent contrast) during pursuit compared with fixation in two extrastriate areas. The results support earlier findings on a motion-specific area in lateral occipitotemporal cortex (human V5). They also point to a further site of activation in a region approximately 12 mm dorsal of V5. The fMRI response in V5 during pursuit is significantly enhanced. This increased response may represent additional processing demands required for the control of eye movements.

Meunier, S.; Pierrot-Deseilligny, E.

doi: 10.1007/s002210050357pmid: 9588776

The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus.

Zaal, Frank T. J. M.; Bootsma, R. J.; van Wieringen, Piet C. W.

doi: 10.1007/s002210050358pmid: 9588777

Prehension involves the coordination of a reaching and a grasping movement, such that the hand opens and closes in tune with the transport of the hand to the object to be grasped. To investigate this coordination, we focused on the transition from hand opening to hand closing in the grasping component of prehension. Earlier research has suggested that the time taken to close the hand remains constant over varying reaching amplitudes. In the present experiment, in which subjects reached for objects at six different distances and for objects that moved away from them at three different, constant speeds, hand-closure time was found to vary as a function of experimental conditions. Moreover, initiation of hand closure did not occur at a constant value of the (perceptually available) first-order time remaining until contact with the object. However, the variations observed, occurring as a function of initial hand-object distance and object speed, could be accounted for by an abstract dynamical model of perceptually driven postural changes.

Helmchen, C.; Rambold, H.; Fuhry, L.; Büttner, U.

doi: 10.1007/s002210050359pmid: 9588778

The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has also been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of different types of eye movements and to distinguish eye movement deficits due to iC impairment from that of the immediately adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integrator hypothesis, all eye movements including the saccadic system and the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye movements deficits after iC lesions, e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in saccade generation? We performed 13 uni- and three bilateral iC inactivations by muscimol microinjections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsional VOR. Under static conditions, unilateral iC injections evoked a shift of Listing’s plane to the contralesional side (up to 20°), which increased (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved. The monkeys showed a spontaneous torsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical eye positions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330–370 ms. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade velocity remained normal and horizontal eye movements were not affected. Bilateral iC injections reduced the shift of Listing’s plane caused by unilateral injections, i.e., back toward the plane of zero torsion. Torsional nystagmus reversed its direction and ceased, whereas vertical nystagmus persisted. In contrast to unilateral injection, there was additional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bilateral injections. The range of stable vertical eye positions and saccade amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation after unilateral iC injections had virtually no effect on torsional and vertical VOR gain and phase at the same time when time constants already indicated severe integrator failure. Torsional VOR elicited a constant slow-phase velocity offset up to 30° toward the contralesional side, i.e., in the opposite direction to spontaneous torsional nystagmus. Likewise, vertical VOR showed a velocity offset in an upward direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional torsional and upward vertical quick phases were missing or severely reduced in amplitude but showed normal velocity. In contrast, bilateral iC injections reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead of 10–20° (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefore appears likely that the vertical and torsional nystagmus after iC lesions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly differential effects on the VOR and the gaze-holding function. These results are not compatible with a single common neural integrator model, which would predict a much stronger VOR gain reduction and phase advance, as found in our data. Our data support the existence of multiple integrators in iC with parallel processing.

Anderson, C. W.; Keifer, Joyce

doi: 10.1007/s002210050360pmid: 9588779

Using an in vitro brainstem-cerebellum preparation from the turtle Chrysemys picta, burst discharge was recorded from the abducens nerve when light was directed on the brainstem. This burst discharge likely represents a neural correlate of the eye-blink reflex. Increasing the intensity of the light stimulus reduced the response latency from a duration of many seconds to approximately 1–2 s. No response was recorded when the light source was covered. The response was present when infrared light was blocked, and it could only be produced when the light spectra contained wavelengths below approximately 550 nm. Lesion experiments reveal that the photosensitive area is located caudal to the trochlear nerve and rostral to the trigeminal nerve. Single-unit microelectrode recordings demonstrate that this region is tonically active in the dark and that activity is suppressed by light. Pharmacological results show that the light response is blocked by application of compounds that act as serotonergic antagonists, and that antagonists of noradrenergic receptors (α or β) either have no effect or their actions are variable. Taken together, these data suggest that an isthmo-optic-like area in the turtle brain is photosensitive to direct light and activates neural circuits that control eye movements.

Bonnefoi-Kyriacou, B.; Legallet, E.; Lee, R. G.; Trouche, E.

doi: 10.1007/s002210050361pmid: 9588780

Three patients with cerebellar limb ataxia and three age-matched controls performed arm-pointing movements towards a visual stimulus during an experimental procedure using a double-step paradigm in a three-dimensional space. Four types of trajectories were defined: P1, single-step pointing movement towards the visual stimulus in the initial position S1; P2, double-step pointing movement towards S1; P3, double-step straight pointing movement towards the second position S2; and P4, double-step pointing movement towards S2 with an initial direction towards S1. We found that the cerebellar patients, as well as the controls, were able to modify their motor programs, but with impaired timing, severe anomalies in the direction and amplitude of the changed movement trajectories and alteration of the precision of the pointing movements.

Seidler-Dobrin, Rachael D.; Stelmach, G. E.

doi: 10.1007/s002210050362pmid: 9588781

Young and elderly subjects performed aiming movements to a visual target with a manipulandum to determine whether the elderly reduce their reliance on visual feedback after extended practice. Reliance on visual feedback was assessed by performance on trials in which the cursor displaying arm movement was unpredictably extinguished. Movements were divided into two subcomponents: a primary, ballistic submovement and a secondary, corrective submovement. For both age groups, removal of visual feedback prior to practice resulted in a decrease in the distance covered in the primary submovement, an increase in the distance of the secondary submovement, and a decrease in endpoint accuracy. After extensive practice with the cursor present, the proportion of distance traveled with the primary submovement was again assessed under trial conditions in which the cursor randomly disappeared. Following practice, the young demonstrated that they were capable of extending the primary submovement distance closer to the target. In addition, primary submovement distance was unaffected by the removal of vision following practice. After practice the elderly did not show evidence of lengthening the primary submovement, and submovement distance and endpoint accuracy continued to be altered by the removal of vision. This suggests that, unlike the young, the elderly do not benefit from practice so that they can place a greater proportion of the movement under program control. Thus, on a relative basis, a greater proportion of their overall movement requires corrective adjustments.

Dengis, Carol A.; Steinbach, M. J.; Kraft, Stephen P.

doi: 10.1007/s002210050363pmid: 9588782

Botulinum toxin is sometimes injected into human eye muscles as an alternative to surgery in the correction of strabismus. Within minutes of botulinum injections into ungulate eye muscles, proprioceptive discharge from muscle spindles decreases dramatically. It is only over 7–48 h, however, that surgically treated strabismus patients usually show an altered proprioceptive signal about eye position, presumably from the palisade endings attached to the global multiply innervated fibers. How quickly will botulinum toxin alter proprioceptive registration of eye position in humans? First, to examine the short-term effects, we measured open-loop pointing responses (which requires knowledge of eye position) in six strabismus patients preinjection and then over a 45 min postinjection period, and in six normal controls over the same time period. Second, to examine the long-term effects, 13 strabismus patients were tested preinjection and then daily over the next 3 weeks, and three normal controls over the same time period. We compared their open-loop pointing responses with the injected eye fixating the target to the photographically determined position of the occluded other eye (a measure of where the patient would point if eye position were determined by efference, not proprioception). There were three groups of patients: esotropes with no previous injection, exotropes with no previous injection, and exotropes with previous injection. First, all patients showed significant correction of their tropias. Second, over the short-term, there was no difference in pointing responses found between the patients and the controls ( t (18) = –1.427, P = 0.1706). Third, over the long-term, however, the difference between the pointing responses and eye position information was compared among the four groups across four posttests and a significant difference found ( F 3,12 = 58.988, P < 0.00001). Only in patients with no previous injections was there altered proprioceptive feedback about eye position. Also, injections into the medial rectus induced a significantly greater proprioceptive response than those injected into the lateral rectus. In humans, botulinum toxin alters proprioception from eye muscles only over the long-term. We suggest that the toxin temporarily affects proprioceptive feedback from palisade endings.

Topka, H.; Konczak, Jürgen; Dichgans, Johannes

doi: 10.1007/s002210050364pmid: 9588783

Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include abnormally increased curvature of hand trajectories and an increased hand path and are thought to originate from an impairment in generating appropriate levels of muscle torques to support normal coordination between shoulder and elbow joints. Such a mechanism predicts that kinematic abnormalities are pronounced when fast movements are performed and large muscular torques are required. Experimental evidence that systematically explores the effects of increasing movement velocities on movement kinematics in cerebellar multijoint movements is limited and to some extent contradictory. We, therefore, investigated angular and hand kinematics of natural multijoint pointing movements in patients with cerebellar degenerative disorders and healthy controls. Subjects performed self-paced vertical pointing movements with their right arms at three different target velocities. Limb movements were recorded in three-dimensional space using a two-camera infrared tracking system. Differences between patients and healthy subjects were most prominent when the subjects performed fast movements. Peak hand acceleration and deceleration were similar to normals during slow and moderate velocity movements but were smaller for fast movements. While altering movement velocities had little or no effect on the length of the hand path and angular motion of elbow and shoulder joints in normal subjects, the patients exhibited overshooting motions (hypermetria) of the hand and at both joints as movement velocity increased. Hypermetria at one joint always accompanied hypermetria at the neighboring joint. Peak elbow angular deceleration was markedly delayed in patients compared with normals. Other temporal movement variables such as the relative timing of shoulder and elbow joint motion onsets were normal in patients. Kinematic abnormalities of multijoint arm movements in cerebellar ataxia include hypermetria at both the elbow and the shoulder joint and, as a consequence, irregular and enlarged paths of the hand, and they are marked with fast but not with slow movements. Our findings suggest that kinematic movement abnormalities that characterize cerebellar limb ataxia are related to an impairment in scaling movement variables such as joint acceleration and deceleration normally with movement speed. Most likely, increased hand paths and decomposition of movement during slow movements, as described earlier, result from compensatory mechanisms the patients may employ if maximum movement accuracy is required.