Espace et Action, Institut National de la Santé et de la Recherche Médicale U94, 69500 Bron, France
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Goffart, Laurent, Denis Pélisson, and Alain Guillaume. Orienting gaze shifts during muscimol inactivation of caudalfastigial nucleus in the cat. II. Dynamics and eye-head coupling. J. Neurophysiol. 79: 1959-1976, 1998. We have shown in the companion paper that muscimol injection in the caudal part of the fastigial nucleus (cFN) consistently leads to dysmetria of visually triggered gaze shifts that depends on movement direction. Based on the observations of a constant error and misdirected movements toward the inactivated side, we have proposed that the cFN contributes to the specification of the goal of the impending ipsiversive gaze shift. To test this hypothesis and also to better define the nature of the hypometria that affects contraversive gaze shifts, we report in this paper on various aspects of movement dynamics and of eye/head coordination patterns. Unilateral muscimol injection in cFN leads to a slight modification in the dynamics of both ipsiversive and contraversive gaze shifts (average velocity decrease = 55°/s). This slowing in gaze displacements results from changes in both eye and head. In some experiments, a larger gaze velocity decrease is observed for ipsiversive gaze shifts as compared with contraversive ones, and this change is restricted to the deceleration phase. For two particular experiments testing the effect of visual feedback, we have observed a dramatic decrease in the velocity of ipsiversive gaze shifts after the animal had received visual information about its inaccurate gaze responses; but virtually no change in hypermetria was noted. These observations suggest that there is no obvious causal relationship between changes in dynamics and in accuracy of gaze shifts after muscimol injection in the cFN. Eye and head both contribute to the dysmetria of gaze. Indeed, muscimol injection leads to parallel changes in amplitude of both ocular and cephalic components. As a global result, the relative contribution of eye and head to the amplitude of ipsiversive gaze shifts remains statistically indistinguishable from that of control responses, and a small (1.6°) increase in the head contribution to contraversive gaze shifts is found. The delay between eye and head movement onsets is increased by 7.3 ± 7.4 ms for contraversive and decreased by 8.3 ± 10.1 ms for ipsiversive gaze shifts, corresponding respectively to an increased or decreased lead time of head movement initiation. The modest changes in gaze dynamics, the absence of a link between eventual dynamics changes and dysmetria, and a similar pattern of eye-head coordination to that of control responses, altogether are compatible with the hypothesis that the hypermetria of ipsiversive gaze shifts results from an impaired specification of the metrics of the impending gaze shift. Regarding contraversive gaze shifts, the weak changes in head contribution do not seem to reflect a pathological coordination between eye and head but would rather result from the tonic deviations of gaze and head toward the inactivated side. Hence, our data suggest that the hypometria of contraversive gaze shifts also might result largely from an alteration of processes that specify the goal rather than the on-going trajectory, of saccadic gaze shifts.
In the companion paper (Goffart and Pélisson 1998 The data were recorded from five cats. The behavioral and physiological methods used in these experiments have been described in the companion paper (Goffart and Pélisson 1998 Target presentation setups
We used two setups to elicit stereotyped, visually triggered gaze shifts without extensive animal training. In the screen setup, the visual target was presented at the edge of a flat, vertical, opaque panel located in front of the animal. With this setup, the target was presented at one of four possible locations, with the two locations along the horizontal meridian representing ~90% of the trials. Screens of different sizes were used to study different target eccentricities, with each screen used in collecting blocks of 20-50 consecutive trials. All screens were square, except the largest one (rectangle). In the hemicylindrical setup, a single, hemicylindrical panel was used during the entire recording session, and the target could be presented in any one of nine holes along a horizontal arc at the level of the animal's eyes. In practice, three locations were used with equal probability, at Data recording and analysis
Visually triggered gaze shifts were recorded during the period between 20 to 120 min after the onset of muscimol injection in the cFN (muscimol session) or the day preceding the injection (preinactivation or control session). Each recording session consisted of a series of 2-s trials, with data acquisition initiated just before target presentation. Horizontal and vertical signals of gaze (eye-in-space), head and target positions, all expressed as angular deviations with respect to the animal's longitudinal body axis, were sampled (frequency = 500 Hz, resolution = 12 bits) and stored in a PC microcomputer.
The following results come from an analysis of the dynamic properties of gaze shifts in 13 experiments. Then the coordination between eye and head is investigated by having measured their contribution to the gaze shift and their relative latency. Finally, the dynamics of eye and head displacements are described.
Gaze dynamics
To illustrate the general features of gaze shift dynamics, the relationship between velocity and position of gaze during the on-going movement is shown in a phase plane plot in Fig. 1. Figure 1A illustrates some rightward gaze trajectories toward a 35° eccentric target and in Fig. 1B some leftward gaze trajectories toward a 19° target, recorded before (
Interaction between gaze dynamics and accuracy
Two of our experiments provided interesting information suggesting a dissociation between gaze dysmetria and changes in gaze dynamics induced by cFN inactivation. In the first experiment (injection I-L1 in left cFN, screen setup), a technical incident occurred in the middle of the postinactivation recording session that permitted the animal to get systematically and permanently visual feedback about its own performance. We then analyzed separately the visually triggered gaze shifts recorded before or after this 15-min period (phases 1 and 2, respectively). Except for this period of continuously visible target stimulation, phases 1 and 2 were identical to the single recording phase of the previously described experiments with the target being turned off at the onset of the gaze shift in ~90% of the trials (see METHODS). In both phases, gaze shift amplitude was strongly and similarly affected by muscimol injection (Fig. 5A). Both the bias (change in y intercept of the relationship between horizontal retinal error and horizontal gaze amplitude) of ipsiversive movements and the reduced gain (change in slope) of contraversive movements were typical of the changes in gaze metrics described in the companion paper. However, in marked contrast to these amplitude characteristics, the dynamics of ipsiversive gaze shifts were impaired differentially in the two postinjection phases. Indeed, the main sequence relationship (Fig. 5B) of leftward movements was strikingly different between the two phases: while gaze dynamics was very little affected in phase 1 (
Eye-head coordination
DYSMETRIA OF THE EYE SACCADE.
The eye and head components of the overall gaze shift were separately analyzed, and it was found that they both contributed to gaze dysmetria. Figure 7 illustrates representative gaze shifts toward a target located 35° to the left (Fig. 7A) or to the right (Fig. 7B), before and after muscimol injection in the left cFN (injection G-L). The observed hypermetria of the leftward gaze shift resulted from hypermetric responses of both eye and head. Similarly, the hypometria of the rightward gaze shift resulted from hypometric responses of both eye and head.
HEAD CONTRIBUTION.
The modifications in eye saccade amplitude described above were paralleled by similar changes in the amplitude of the head movement, keeping the contribution of the head to the gaze shift nearly unaffected. This is illustrated in Fig. 9 by plots of the horizontal displacement of the head during the gaze shift (head contribution) as a function of the amplitude of horizontal gaze displacement for experiments G-L (Fig. 9A) and I-L2 (Fig. 9B). One can first note that the head substantially contributed to gaze shifts as small as 10° in amplitude, which is typical in the cat. For larger gaze movements up to the limit of the tested range, there was an almost linear increase of head contribution with gaze shift amplitude. Second, only some moderate changes in the contribution of the head can be seen during cFN inactivation as compared with control data (increase for contraversive gaze shifts in cat G and decrease for ipsiversive gaze shifts in cat I). These differences have been quantified in each experiment by a linear regression analysis performed separately on rightward and leftward responses. For cat G (Fig. 9A), this analysis led to the following equations: y =
EYE-HEAD DELAY
We then investigated whether the temporal coupling between eye and head movements was affected by muscimol injection. The delay between the onset of eye saccade (gaze movement onset) and the onset of head movement (difference eye onset time
Eye and head movement dynamics
The dynamics of ocular and cephalic components of gaze shifts are separately illustrated in Figs. 12 and 13, respectively. The data for these eye and head main sequence relationships have been drawn from the same left cFN inactivation experiments described above in Figs. 2, 4, 8, and 9. Figure 12 shows the main sequence relationships of the eye saccade recorded in experiments G-L (Fig. 12, A and B) and I-L2 (Fig. 12, C and D); and Fig. 13 depicts the relationship between the amplitude of the total horizontal head displacement and its maximum velocity for the same experiments (G-L: Fig. 13A and I-L2: Fig. 13B). Comparisons between control and pharmacological relationships, for both eye and head, resulted in the same observations made above for gaze main sequences (Fig. 2). First, contraversive movements showed identical dynamic characteristics as control responses. Second, the velocity of ipsiversive movements tended to be slower than that of control movements of comparable amplitude, and their duration was slightly prolonged. These modifications of eye and head main sequence characteristics for ipsiversive responses indicate that changes in gaze shift dynamics result from parallel changes of eye and head components.
Three major findings have been illustrated in this paper. First, gaze dysmetria induced by muscimol injection in the cFN was the result of strongly dysmetric movements of both the eye and head without large changes in the relative contribution of these two segments to the overall gaze shift. Second, cFN inactivation can lead to small but consistent changes in the relative timing between eye and head movement onset. Third, a slight slowing in gaze displacements was noted for both ipsiversive and contraversive movements. This small change in gaze dynamics was the result of changes in movements of both the eye and head.
Involvement of the cFN in the control of eye and head movements
For the first time, our data provide direct evidence that cFN is not only involved in oculomotor control but also in the control of head movements. Previous pharmacological manipulations of cFN activity were performed in the head-restrained animal and therefore could not make this distinction (Ohtsuka et al. 1994 Gaze shift control versus separate eye and head movements controls?
The fact that the cFN inactivation did not lead to consistent changes in the relative contribution of the eye and head to the amplitude of ipsiversive gaze shifts implies that the caudal fastigial control on these movements is achieved either by tuning a gaze-related motor command before it is subdivided into signals driving eye and head controllers separately or by controlling both eye- and head-related signals in a remarkably well-balanced fashion. The first possibility suggests that the cFN influences a structure controlling ipsiversive coordinated eye-head movements. The existence of both the crossed fastigio-tectal projections and the longer fastigio-thalamo-cortico-tectal route described above might support this proposed influence because the deep superior colliculus is thought to issue commands related to gaze, rather than eye, displacement (Freedman and Sparks 1997b Gaze dynamics and the level(s) of cFN involvement in saccadic control
We now will discuss how the results of our analyses of gaze shift dynamics compare with predictions, presented in the INTRODUCTION, of various hypotheses about the level of cerebellar contribution. Considering first gaze shifts directed away from an inactivated cFN, our data on gaze dysmetria (companion paper) and those of Robinson et al. (1993) Conclusions
Because of the weak changes in movement dynamics and in the main parameters describing eye-head coordination (head contribution, eye/head delay), we propose that the gaze dysmetria induced by muscimol injection in the cFN results from an impairment in the processes that specify the metrics of an impending gaze shift rather than from a deficit in the mechanisms that control on-line eye and head trajectories. This suggestion fits well with the hypothesis that we proposed to account for both the hypermetric bias of ipsiversive gaze shifts and the gaze fixation offset. We suggest that the medioposterior cerebellum contributes to the elaboration of a reference signal that is used for the production of visually guided ipsiversive gaze shifts. This prominent contribution to the programming of impending gaze shifts does not exclude any additional role in the control of the on-going gaze shift. Concerning contraversive gaze shifts, this hypothesis could not be predicted from the sole analysis of gaze dysmetria but constitutes the most parsimonious explanation of the data presented here.
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
), we showed that muscimol injection in the caudal fastigial nucleus (cFN) strongly affected the accuracy of saccadic gaze shifts. Gaze shifts directed toward the injected side overshot the target by a constant horizontal error and converged onto a shifted, erroneous goal. A bias also was present for the movement of the head that accompanied the gaze shift and when the animal positioned its mouth with respect to a piece of food. These deficits led us to propose that cFN contributes to the specification of the goal during the preparation of an ipsiversive gaze shift. On the other hand, gaze saccades directed away from the inactivated cFN were hypometric. But in that case, gaze undershot the target by an error that depended on the required gaze displacement, and this deficit could be expressed as a reduced gain of the relationship linking gaze displacement amplitude to retinal error. A reduction of saccadic gain has been reported previously for saccadic eye movements performed in the head-restrained condition (Robinson et al. 1993
). However, the functional origin of this contraversive hypometria is not clear as hypometria could result from an alteration of processes that either specify the metrics of the impending gaze shift, from an impaired control of the on-going eye and head trajectories, or from both.
), in close analogy to the feedback system proposed for saccadic eye movements performed with the head restrained (Jürgens et al. 1981
; Robinson 1975
; Zee et al. 1976
). According to this hypothesis, gaze is monitored continuously throughout its displacement and compared with a reference signal (target position or desired gaze displacement), which results in a signal of current gaze position relative to the target (dynamic gaze motor error). In turn, gaze motor error would ensure gaze accuracy by driving eye premotor neurons (Laurutis and Robinson 1986
; Pélisson et al. 1988
; Tomlinson 1990
), both eye and head premotor neurons (Guitton et al. 1990
), or neurons modulating the vestibuloocular reflex (Phillips et al. 1995
). Despite these differences, all these models embody the gaze feedback concept by combining the local feedback loop of saccadic eye movement models with another feedback pathway providing head-related information.
) or to spinocerebellar degeneration disease (Zee et al. 1976
). Second, an impairment along the feedforward path but downstream from the feedback loop should cause large changes in both the dynamics and the metrics of saccades. Third, changes in gaze accuracy and dynamics also are expected if the feedback pathway itself is subject to some dysfunction. Indeed, simulations of feedback models showed that changing the feedback gain from its nominal value significantly affected both the accuracy and dynamics of saccades (Keller 1989
; Moschovakis 1994
). Fourth, a central dysfunction at a level situated upstream from the feedback loop, that would alter the encoding of the reference signal driving the feedback controller, has predictable effects on the accuracy, but not the dynamics, of the resulting movements (Optican 1982
). Therefore an analysis of the dynamics of orienting movements recorded during cFN inactivation could help to understand the role of the cerebellum in the control of gaze shifts. Recently, in a model based on burst activity and inactivation data of the cFN in monkey, Dean (1995)
proposed that the late and the early burst of cFN activity could directly affect the saccadic pulse generator to help decelerate ipsiversive saccades and accelerate contraversive ones, respectively. Although the effects of simulated unilateral fastigial lesions were not quantified, it can be expected that the removal of the late burst (lagging saccade onset) normally produced by cFN neurons in relation to ipsiversive saccades would prolong the deceleration phase of these responses and, in effect, alter their dynamics (see Robinson et al. 1993
). Conversely, no straightforward predictions can be made from this model regarding a possible effect of cFN inactivation on contraversive saccade dynamics.
). It is, therefore, possible to test whether medial cerebellar regions are involved specifically in the control of saccadic eye movements or in the more general function of orienting gaze in space. To our knowledge, there was only one qualitative report of coordinated eye-head movements after cerebellar lesions in the monkey (Ritchie 1976
) that suggested no change in saccadic dysmetria as compared with a head-restrained condition. In human cerebellar patients, two clinical studies led to different observations: Shimizu et al. (1981b)
reported a similar gaze dysmetria whether the head was restrained or not, whereas in another study, a difference between the two testing conditions was observed in some patients when hypometric movements were considered (Shimizu et al. 1981a
). However, in none of these studies was the actual head contribution to the gaze shift investigated.
).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). Detailed in the following sections are the conditions of target presentation and information regarding the analyses performed in the present paper.
24, 0, and 24° relative to the animal's midsagittal plane. At the start of a trial, one of the nine holes could be used to present an object that served to control initial gaze position. In both setups, the ambient illumination could be interrupted by triggering an electronic shutter at the beginning of the visually elicited gaze response, and the lights were relit 2 s after target presentation. In these trials (probability of ~90%), any immediate visual feedback about motor performance was suppressed.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
) and after (
) muscimol injection (injection I-L1 in left cFN). Because cFN-inactivated gaze shifts were highly dysmetric, we included for comparison preinactivation gaze responses with similar amplitude (
, target presented at 19 and 35° in left and right panels, respectively). First, examination of the control responses showed that trajectories to different targets diverged only after ~2-3° of displacement, when gaze velocity (~300°/s) was still increasing quickly. A quite similar early separation of gaze trajectories was observed when comparing control and cFN-inactivated responses elicited by a single target, which indicated that muscimol-induced modifications in gaze trajectory were expressed nearly at movement onset. In contrast, a striking resemblance was observed between control and cFN-inactivated gaze trajectories that achieved the same total amplitude. This close matching was observed from the beginning until the completion of the movement, which held for both ipsiversive and contraversive responses. Only a slight reduction in gaze velocity was noted for ipsiversive gaze shifts. Based on these individual examples, it was thus virtually impossible to differentiate the dynamics of dysmetric gaze shifts performed after cFN inactivation from the dynamics of control responses with comparable metrics.
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FIG. 1.
Phase plane plots of horizontal gaze shift trajectories [inactivation of the left caudal part of the fastigial nucleus (cFN) experiment I-L1]. In each panel, instantaneous gaze velocity is plotted vs. gaze position (500-Hz sampling frequency). Responses with similar starting position have been selected in the control and pharmacological sessions. A: rightward gaze shifts: 2 cFN-inactivated ( ) and 2 control responses (
) toward a 35° eccentric target are superimposed; additionally, 2 control responses toward a 19° eccentric target (
) have been selected as they match cFN-inactivated movement amplitude. B: leftward gaze shifts: 2 cFN-inactivated (
) and 2 control responses (
) toward a 19° eccentric target are superimposed; additionally, 2 control responses toward a 35° eccentric target (
) have been selected as they match cFN-inactivated movement amplitude. Note that, for a given target, cFN-inactivated trajectories diverge from control ones during the acceleration phase and conversely, for a given movement amplitude, cFN-inactivated and control trajectories are similar.
and
, respectively). The two movement directions can be distinguished by the sign of gaze amplitude, which is, by convention, positive for rightward movements and negative for leftward movements. It should be noted that gaze shifts elicited by a sudden target presentation reached a very high speed with a small variability. This general feature reflects a time-optimal control strategy that is seen in the cat behaving in "ecological" testing conditions (head unrestrained, food target) (Guitton et al. 1990
). Regarding the effect of cFN inactivation on these relationships, no marked difference was noted between the control and muscimol data. For contraversive (rightward) movements, the two clusters of muscimol and control data points closely overlapped for gaze duration and peak velocity. For ipsiversive (leftward) movements, the overlap between control and muscimol data are less obvious. This is observed mainly in the data of cat G with a reduced peak velocity (Fig. 2A) and an increased duration (Fig. 2B) after muscimol injection. For the other animal, a similar, though weaker, tendency was observed for large amplitude movements. The reliability of these individual observations was tested by the following global analysis. For each experimental condition (control and muscimol), the responses were first sorted according to their vectorial amplitude into 10° width classes. Second, maximum vectorial velocity of gaze was computed for each class that included at least three movements (valid bin). The between-condition difference (muscimol minus control) of gaze maximum vectorial velocity was computed for each valid bin. Figure 3 illustrates these velocity difference values plotted against gaze shift amplitude (bin centers). For each bin,
correspond to single experiments and
to the grand mean computed over the different experiments. It should be noted that the difference values were quite variable between experiments, showing that the maximum velocity is increased during cFN inactivation for some experiments and decreased for others; however, for both contraversive and ipsiversive responses (negative and positive abscissas, respectively), grand means of differences in gaze maximum velocity are negative, indicating a trend toward reduced velocities during cFN inactivation. To assess the statistical significance of this observation, gaze maximum vectorial velocity was submitted to an ANOVA (see METHODS) for each of the three amplitude bins that provided the largest number of observations (centered on 10, 20, and 30°). Among the threeANOVAs (Table 1), those for the classes of 10° and 20° amplitude gaze shifts revealed a small, but statistically significant, effect of the experimental conditions (muscimol vs. control) factor [F(1,6) = 8.7, P < 0.05; and F(1,12) = 7.2; P < 0.05, respectively). Neither movement direction nor any interaction between movement direction and experimental condition reached a statistical significance level. In summary, the cFN inactivation produces a moderate (55°/s on average) decrease of the maximum velocity of both ipsiversive and contraversive movements, a decrease that reached a statistically significant level for two of the three classes of amplitude tested.
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FIG. 2.
Gaze main sequence relationships in 2 left cFN inactivation experiments (A and B: injection G-L, screen setup; C and D: injection I-L2 hemicylindrical setup). Maximum horizontal gaze velocity is plotted vs. the amplitude of the horizontal component of gaze shifts (A and C), and duration is plotted vs. amplitude of vectorial component (B and D). Amplitudes are negative or positive for leftward or rightward movements, respectively. Note the slight reduction of peak velocity and increase of duration for leftward (ipsiversive) responses.
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FIG. 3.
Summary of gaze maximum velocity changes after muscimol injection. The between-condition (muscimol minus control) difference of gaze maximum vectorial velocity is plotted against gaze shift amplitude for several 10° amplitude bins (negative values correspond to muscimol-induced reductions in gaze velocity). Each set of - - corresponds to a single session relationship, and the overall relationship (all 13 experiments pooled together) is shown by -
-. Note that data points in each amplitude bin were computed with a minimum number of 3 control and 3 cFN-inactivated gaze shifts. Negative and positive amplitude values correspond to contraversive and ipsiversive responses, respectively.
View this table:
TABLE 1.
Summary of gaze main sequences
27.5 ± 10.4°, n = 103 for muscimol vs.
26.0 ± 8.1°, n = 82 for control), the duration of the acceleration slightly decreased [26 ± 4 ms vs. 28 ± 4 ms, t(183) = 4.13, P < 0.001]. The modesty of this difference is illustrated in Fig. 4A (negative amplitude values) by the overlap between the control and muscimol data points. In contrast, the duration of deceleration largely increased after muscimol injection [82 ± 16 ms vs. 61 ± 11 ms, t(183) =
10.11, P < 0.001] as indicated by the upward shift of data points with respect to the control (Fig. 4B, negative amplitudes). These results indicate that the change in dynamics of ipsiversive gaze shifts reported after injection G-L (see Fig. 2, A and B) result from a slowing that is restricted to the deceleration phase. Regarding contraversive gaze shifts, when one considers matched amplitude displacements (21.4 ± 3.5° vs. 22.5 ± 4.6°, n = 91 for muscimol, n = 64 for control), there is no statistically significant change in the acceleration duration [29 ± 5 ms vs. 28 ± 5 ms, t(153) = 0.82, P > 0.05] nor in the deceleration duration [48 ± 9 ms vs. 49 ± 10 ms, t(153) = 0.56, P > 0.05]. This similarity of acceleration and deceleration phases is illustrated by the overlap between the control and muscimol data (Fig. 4, A and B: positive amplitude values). Finally, the ratio of the acceleration duration to the total saccade duration is plotted as a function of horizontal gaze amplitude for experiments G-L and I-L2 in Fig. 4, C and D, respectively. For matched gaze displacement amplitudes (see earlier text), this skewness ratio (Hashimoto and Ohtsuka 1995
) is reduced significantly [0.24 ± 0.04 vs. 0.32 ± 0.05, t(183) = 11.38, P < 0.001] for ipsiversive gaze shifts but unchanged for contraversive gaze shifts [0.375 ± 0.078 vs. 0.371 ± 0.075, t(153) = 0.29, P > 0.05] recorded after injection G-L (Fig. 4C). This difference between ipsiversive and contraversive gaze shifts was not observed after injection I-L2 (Fig. 4D): muscimol injection did not change the skewness ratio of matched amplitude ipsiversive gaze shifts[0.37 ± 0.10 vs. 0.38 ± 0.09, t(95) = 0.74, P > 0.05] or contraversive gaze shifts [0.39 ± 0.10 vs. 0.36 ± 0.07, t(97) =
1.48, P > 0.05]. In conclusion, the slowing of ipsilateral gaze shifts after injection G-L resulted primarily from an increased duration of the deceleration phase relative to the total gaze displacement duration. This observation is compatible with the hypothesis that cFN activity contributes to the deceleration of ipsilateral saccades (Robinson et al. 1993
). However, these data do not imply that this contribution is linked to any control of the accuracy and hence that the hypermetria described in the companion paper result form a flawed deceleration phase. In the next section, some evidence for a dissociation between dysmetria and changes in dynamics properties is provided.
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FIG. 4.
Gaze shift dynamics during acceleration and deceleration phases and skewness ratio (left cFN inactivation). Duration of the acceleration phase is plotted as a function of the amplitude of horizontal gaze acceleration displacement (A) and the duration of the deceleration phase as a function of the amplitude of the horizontal gaze deceleration displacement (B) for experiment G-L. Ratio between acceleration duration and total saccade duration is plotted as a function of horizontal gaze amplitude in C and D for experiments G-L and I-L2, respectively. Negative or positive values indicate leftward or rightward movements, respectively.
), a marked reduction of gaze dynamics was observed in phase 2 (
). Note, however, that for contraversive movements, data from both testing phases overlapped the control data (·). We verified in another cat (cat L) whether these changes in movement dynamics effectively resulted from visual feedback. We recorded the gaze shifts generated before and after muscimol injection in the right cFN. The muscimol session comprised two phases (phases 1 and 2) separated by a period of 15 min during which the animal's orienting behavior was tested with the lights permanently lit. In Fig. 5C, the relationship between horizontal retinal error and horizontal gaze amplitude is plotted for the control session and for both muscimol phases. As for injection I-L1, the amplitude of gaze shifts was affected similarly in phases 1 and 2: the y intercept and slope values were quite similar for ipsiversive movements, and a slight reduction of slope also was noted for contraversive movements. Figure 5D illustrates the changes in dynamics that occurred between the two phases, changes that concern only the ipsiversive (rightward) gaze shifts. During phase 1, the velocity of ipsiversive gaze shifts was, on average, increased as compared with the control data, whereas phase 2 was characterized by a marked reduction in velocity. In summary, these two particular experiments provide examples of dramatic changes in the dynamics of ipsiversive gaze shifts that developed during the inactivation period and that could not be related to modifications in gaze metrics. Figure 6 reveals the detailed dynamic properties of gaze shifts for the same experiments (top: cat I, bottom: cat L). The duration of the acceleration is plotted as a function of the amplitude of the acceleration phase (Fig. 6, A and C) and the duration of the deceleration as a function of the amplitude of the deceleration phase (Fig. 6, B and D). For matched amplitude ipsiversive gaze shifts, the duration of the acceleration did not change between phases 1 and 2 [cat I: 32 ± 15 ms for phase 1 vs. 37 ± 22 ms for phase 2, t(152) =
1.52, P > 0.05; cat L: 27 ± 14 ms for phase 1 vs. 30 ± 20 ms for phase 2, t(84) =
0.70,P > 0.05], whereas the duration of deceleration significantly increased [cat I: 54 ± 22 ms vs. 82 ± 36 ms, t(152) =
5.44, P < 0.001; cat L: 89 ± 33 ms vs. 110 ± 42 ms,t(84) =
2.43, P < 0.02]. The skewness ratio was significantly reduced between phases 1 and 2 in cat I [0.38 ± 0.10 vs. 0.32 ± 0.11, t(152) = 3.48, P < 0.001] but unchanged in cat L [0.24 ± 0.09 vs. 0.22 ± 0.11, t(84) = 0.78, P > 0.05]. In conclusion, the pronounced change in the main sequence relationship during the second phase (as illustrated in Fig. 5, B and D) essentially resulted from a marked reduction in gaze velocity during the deceleration phase. These changes in dynamics were not associated with any significant change in accuracy.
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FIG. 5.
Spatial and dynamic properties of gaze shifts before and after muscimol injection in the left cFN of cat I (injection I-L1) or in the right cFN of cat L. A and C: plots of horizontal displacement amplitude of gaze shifts vs. horizontal retinal error (A: data from cat I, C: data from cat L). Three such plots are shown superimposed for preinactivation (control) responses and for responses recorded during 2 cFN-inactivated phases (detailed in text). B and D: gaze main-sequence relationships: maximum velocity vs. amplitude relationships plotted for the control session and for the 2 cFN inactivated phases (B: data from cat I, D: data from cat L).
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FIG. 6.
Detailed dynamic properties of gaze shifts for the same sessions as in Fig. 5. Duration of the acceleration is plotted as a function of the horizontal gaze displacement achieved during the acceleration phase in A and C for injection in cat I and L, respectively. Duration of the deceleration is plotted as a function of the horizontal gaze displacement achieved during deceleration in B and D. Negative or positive values indicate leftward or rightward movements, respectively.
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FIG. 7.
Temporal trajectories of eye, head, and gaze orienting movements (left cFN inactivation, experiment G-L). These horizontal trajectories are those from responses toward a 35° eccentric target presented to the left (A) or to the right (B). Control and cFN-inactivated responses are shown by thin and heavy lines, respectively. Responses are aligned on gaze shift onset . Room lights were switched off at gaze shift onset (see METHODS) and no correction saccade was observed.
). Those responses were respectively associated with the inappropriately triggered and the misdirected gaze responses described in the previous paper. For small retinal errors (range = ±5°), the average amplitude of eye saccades was
12.6 ± 2.9° (n = 21) after muscimol injection in the left cFN of cat G (Fig. 8A) and
7.0 ± 2.2° (n = 19) after injection in the left cFN of cat I(Fig. 8C).
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FIG. 8.
Relationships between horizontal retinal error and horizontal eye amplitude illustrated for the same left cFN inactivation sessions as in Figs. 2 and 4 (A and B: experiment G-L; C and D: experiment I-L2). In each panel, the horizontal amplitude of the saccadic eye displacement is plotted vs. horizontal retinal error; control and cFN-inactivated data are shown by and
, respectively. Leftward (negative values) and rightward (positive values) movement directions are shown in separate panels (A and C and B and D, respectively).
0.63x
3.92 (r2 = 0.92) and y = 0.54x
1.38 (r2 = 0.89) for leftward and rightward control movements, respectively, and y =
0.58x
1.57 (r2 = 0.87) and y = 0.64x
2.07 (r2 = 0.90) for corresponding (ipsiversive and contraversive) cFN-inactivated gaze shifts, respectively. For cat I (Fig. 9B), the equations of the control relationships were y =
0.65x
4.10 (r2 = 0.93) and y = 0.55x
2.93 (r2 = 0.94) for the leftward and rightward responses respectively, whereas the respective equations were y =
0.67x
5.73 (r2 = 0.96) and y = 0.53x
2.00 (r2 = 0.89) for the muscimol data.
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FIG. 9.
Contribution of the head to total gaze displacement illustrated for the same left cFN inactivation experiment as in Figs. 2, 4, and 8 (A: injection G-L and B: injection I-L2). For each control and muscimol session, the absolute value of the horizontal amplitude of concurrent head displacement is plotted vs. horizontal gaze displacement; leftward and rightward responses indicated by negative and positive gaze displacements, respectively.
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FIG. 10.
Contribution of the head to total gaze displacement: summary of regression parameters describing the relationship between amplitude of head movement contribution and gaze shift amplitude. Slope (top) and x intercept (bottom) absolute values are shown for control ( ) and pharmacological (
) sessions. Ipsiversive and contraversive responses are shown in A and B, respectively.
head onset time) was computed for each gaze shift. Figure 11 summarizes the results for all the experiments. In general, preinjection responses were characterized by a positive delay between eye and head (i.e., head moved on the average 11 ms before the eyes). The delay between the eye and head movements for ipsiversive gaze shifts very often changed relative to the respective control values: all eight statistically significant differences indicated a reduction of this delay (Fig. 11A). However, the mean reduction averaged across all experiments amounts to only 7.3 ± 7.4 ms [4.4 ± 8.5 vs. 11.7 ± 9.1, paired t-test: t(12) = 3.56, P < 0.01] compatible with a lessened head contribution after cFN inactivation. On the other hand, cFN inactivation tended to increase eye/head delay for contraversive responses [20.2 ± 12.3 vs. 11.9 ± 9.7, t(12) = 2.95, P < 0.05] compatible with an enhanced head contribution, but again the mean change was small (8.3 ± 10.1 ms) and reaches a statistically significant level for only five experiments (Fig. 11B). A statistically significant correlation (Pearson correlation coefficient r =
0.61, P < 0.05) was found between the difference in eye-head delay of contraversive gaze shifts and the difference in x intercept observed in the relationship between head contribution and amplitude of contraversive gaze shifts (see preceding paragraph). This negative correlation means that the greater head contribution to the amplitude of contraversive gaze shifts after muscimol injection is associated with the fact that it starts earlier relative to the eye.
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FIG. 11.
Temporal coupling between eye and head movement initiation. Delay computed from eye (or gaze) saccade onset to head movement onset is plotted separately for control ( ) and pharmacological (
) sessions. Ipsiversive and contraversive responses are shown in A and B, respectively. *, statistically significant differences between the cFN inactivation and the corresponding control session (Student's t-test: *P < 0.05, **P < 0.01, ***P < 0.001, NS: P > 0.05).
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FIG. 12.
Eye saccade main sequence relationships in the same left cFN inactivation experiments as in Figs. 2, 4, 8, and 9 (A and B: injection G-L, screen setup; C and D: injection I-L2 hemicylindrical setup). Maximum velocity is plotted vs. amplitude of eye saccade horizontal component (A and C), and duration is plotted vs. amplitude of vectorial component (B and D). Amplitudes are negative or positive for leftward or rightward movements, respectively. Note the slight reduction of peak velocity and increase of duration for leftward (ipsiversive) responses.
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FIG. 13.
Head main sequence relationships. Same responses and conventions as in Figs. 2, 4, 8, 9, and 12 (A: injection G-L; B: injection I-L2).
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; Robinson et al. 1993
; Sato and Noda 1992
). In one primate study, saccadic eye movements have been measured in both head-restrained and -unrestrained conditions after a more extensive cerebellar lesion. The author concluded that the "postoperative error in the accuracy of the initial saccadic response to a particular target displacement was the same whether or not the head was immobilized" (Ritchie 1976
). However, because it was not mentioned whether the head significantly contributed to these gaze shifts and whether head movements themselves were affected by the lesion, it was not possible to draw firm conclusions from this experiment.
; Fukushima et al. 1977
; Matsushita and Hosoya 1978
). In addition, the cFN projects to the contralateral nucleus reticularis gigantocellularis (Homma et al. 1995
) and to the deep layers of both superior colliculi (Hirai et al. 1982
; Kawamura et al. 1982
; May et al. 1990
; Roldan and Reinoso-Suarez 1981
; Sugimoto et al. 1982
; but see Noda et al. 1990
1). Both structures have been implicated in head movement control (Cowie and Robinson 1994
; Drew and Rossignol 1990
; Freedman and Sparks 1997b
; Freedman et al. 1996
; Grantyn and Berthoz 1987
; Guitton 1992
; Isa and Sasaki 1988
; Peterson 1977
; Roucoux et al. 1980
; Segraves and Goldberg 1992
; Suzuki et al. 1989
). Finally, ascending projections of the cFN through the thalamic ventro-median (VM) nucleus contact three cortical areas: the ventral bank of the cruciate sulcus, the fundus of the presylvian sulcus, and the ventral bank of the ectosylvian sulcus (Kyuhou and Kawaguchi 1987
; Steriade 1995
) that, in turn, all project to the deep layers of the superior colliculus (Harting et al. 1992
; Segal et al. 1983
; Tortelly et al. 1980
). The fundus of presylvian sulcus itself was suggested to participate in head movement control(Guitton and Mandl 1978
).
), the majority of neurons found in the caudal part of the fastigial nucleus discharge in relation to passive ipsiversive head movements, to contraversive saccades, and to contralateral eye fixations (type I eye position velocity neurons). However, the electrophysiological properties of these neurons, as well as that of other fastigial neurons, have never been investigated in the head-unrestrained animal. A clue to these properties can be provided by the nature of the signals carried by mossy fibers to the oculomotor vermis and the fastigial nucleus. In addition to teleceptive information about external stimuli (Donaldson and Hawthorne 1979
; Freeman 1970
), mossy fiber input consists of extraocular and neck proprioceptive signals (Batini et al. 1974
; Berthoz and Llinas 1974
; Schwarz and Tomlinson 1977), vestibular signals (Gould 1980
; Kotchabhakdi and Walberg 1978
), and signals from reticular nuclei (Batini et al. 1978
; Blanks 1988
; Brodal et al. 1986
; Carpenter and Batton 1982
; Dietrichs and Walberg 1987
; Gerrits and Voogd 1987
; Gould 1980
; Van der Want et al. 1987) that could possibly provide copies of eye and head motor commands. This convergence of various signals related to the position and/or displacement of eye and head is compatible with the medioposterior cerebellum playing a role in the control of eye and head displacements.
; Freedman et al. 1996
; Munoz et al. 1991
; Paré et al. 1994
; Roucoux et al. 1980
). The hypothesis of a fastigial influence on the superior colliculus already has been formulated to account for the bias of ipsiversive gaze shifts and the gaze fixation offset observed during fastigial inactivation (see companion paper). Regarding contraversive movements, the change in the contribution of head to the total gaze shift amplitude is so slight (<2°), that the issue of whether the cFN directly controls gaze or separately affects eye and head controllers, is questionable. The fact that, for these contraversive movements, the head starts earlier with respect to the eye, might contribute to this slight increase in head contribution because this difference in eye-head delay correlates with the difference in x intercept of the head contribution-gaze amplitude relationship. It is likely that these changes in eye-head coupling result from the tonic deviations of gaze and head toward the inactivated side. Indeed, we have shown in the companion paper that when the head is deviated, the eye is deviated in the same direction. This orbital eye deviation could be responsible for the increased contribution of the head to gaze shifts in the opposite direction [see Freedman and Sparks (1997a)
for an extensive analysis of this effect in the monkey] and also for the increase in eye-head delay (head starting earlier). The ipsilateral fastigio-tectal and fastigio-thalamic projections are compatible with the cFN acting upstream from the decomposition of desired gaze displacement commands into separate eye and head signals, for the same reasons as reported above for gaze shifts toward the injected side. The crossed cFN projections both to the reticularis pontis oralis and reticularis pontis caudalis nuclei (Rho et al. 1996
) and to the reticularis gigantocellularis nucleus (Homma et al. 1995
) also might convey an influence of the cFN on eye (Cullen et al. 1993
; Grantyn and Berthoz 1987
; Kaneko et al. 1981
; Vidal et al. 1983
; Yoshida et al. 1982
) and head movements (Drew and Rossignol 1990
; Grantyn and Berthoz 1987
; Grantyn et al. 1992a
,b
; Isa and Sasaki 1988
; Iwamoto and Sasaki 1990
; Peterson 1977
; Peterson et al. 1978
; Siegel and Tomaszewshi 1983; Suzuki et al. 1989
). For these crossed reticular projections, the question whether cFN controls gaze or eye and head separately remains unanswered, since the nature of the signals encoded at these levels is still unknown.
; Noda et al. 1988
).
suggest the reduction of a gain along the visuomotor pathways. In the framework of feedback models where the accuracy of gaze shifts is ensured by the operation of a gaze feedback loop (see INTRODUCTION), gaze hypometria can result from a gain increase along this negative feedback pathway, from a gain decrease of both eye and head motor commands downstream from the feedback loop, or from a reduction in the reference signal that drives the gaze (or separate eye and head) controller(s). The first possibility of a cerebellar-dependent gain located along the feedback pathway has been proposed by some authors (Keller et al. 1983
; Vilis and Hore 1981
) to account for saccadic dysmetria in the head-restrained monkey. Accordingly, the hypometria would result from an overestimation of the eye displacement that has occurred since the beginning of the movement. Based on simulation data, Keller (1989)
predicted that the maximum velocity of the eyes, as compared with their total displacement, should be relatively spared by an increased feedback gain, leading to a slight increase in peak velocity in the main sequence relationship. In contrast, the modification we observed after muscimol injection, although subtle, is clearly incompatible with this hypothesis as we found a slowing of gaze shifts. Our data are not compatible either with a reduction of the gain, at a level downstream from the saccade feedback generator, of both eye and head motor commands because the predicted dramatic change in the main sequence relationships was not observed (e.g., a twofold decrease in gain should lead to movements of half the size of, but with the same duration as, control responses to the same target eccentricity). Moreover, the fact that fastigial or vermal electrical microstimulation evokes saccadic eye movements (Fujikado and Noda 1987
; Noda et al. 1988
) and not ramp eye movements
as would be expected if the activation was confined downstream from the pulse generator (Cohen and Komatsuzaki 1972
)
is not compatible with this possibility either. Nonetheless, such a peripheral cFN action was proposed by Noda et al. (1991)
to account for the lack of compensation for saccades induced by fastigial stimulation during the preparation of a goal-directed saccade [Mays and Sparks paradigm (Mays and Sparks 1980
)]. However, these authors did not consider that this compensation failure also could result from a change in the reference signal that drives the saccadic controller, upstream from the dynamic feedback loop. Our contraversive movements data favors this last hypothesis of a cFN-dependent element located upstream from the local feedback loop (see also Optican 1982
). From this perspective, the hypometria observed after muscimol injection in the cFN would result from an impaired specification of the reference signal that drives the gaze (or separate eye and head) controller(s). The slight modification in movement dynamics we observed after unilateral muscimol injection in the cFN for both ipsiversive and contraversive gaze shifts (average velocity decrease = 55°/s) might possibly result from nonspecific factors such as a decreased arousal (Crommelink and Roucoux 1976) or from an effect of visual feedback (see further).
). Some authors (Fuchs et al. 1993
; Helmchen et al. 1994
; Ohtsuka and Noda 1995
) have proposed that the late saccadic burst generated by the cFN neurons during ipsiversive saccades (Fuchs et al. 1993
; Helmchen et al. 1994
; Hepp et al. 1982
; Ohtsuka and Noda 1991
) could be involved in stopping the saccade and, accordingly, its suppression by muscimol would lead to the observed ipsilateral hypermetria (Robinson et al. 1993
). Note that, because this late burst has been shown to lead saccade completion by a constant time of ~30 ms (Ohtsuka and Noda 1991
) or by a time that increases with saccade size (Fuchs et al. 1993
), the postulated hypermetria should be bigger for intended larger saccades because those are faster at the time of late burst onset. The slight slope increase in the relationship between horizontal retinal error and horizontal gaze amplitude of ipsiversive gaze shifts, although much less pronounced than the change in y intercept (see companion paper), is consistent with this hypothesis and suggests that the cFN neurons also generate a late burst during an ipsiversive head-free gaze shift.
; Burde et al. 1975
; Goldberg et al. 1993
; Optican 1982
; Optican and Robinson 1980
; Vilis and Hore 1981
; Westheimer and Blair 1974
) [note, however, that Robinson et al. (1993)
reported some changes in saccade dynamics after muscimol injection in the primate cFN]. Based on these considerations from previous studies and on some peculiar observations of our own (described in the following text), we propose that these modifications in dynamics and the dysmetria of gaze shifts during cFN inactivation constitute two distinct deficits that do not completely relate to each other. First, the slight slowing of gaze velocity contrasts with the severity of the gaze dysmetria reported in the companion paper. In particular, the inappropriately triggered and misdirected gaze shifts, which most clearly illustrate the cFN-induced spatial deficit, have similar dynamics as other gaze shifts. Second, for two experiments testing the effect of visual feedback, gaze dynamics evolved independently of the amount of gaze dysmetria: the velocity was reduced markedly after allowing visual feedback for ~15 min but virtually no associated change in dysmetria was seen. We speculate that these modifications in gaze dynamics were induced by some corrective mechanisms triggered by the short exposure to visual feedback to compensate for the dysmetria (Straube and Deubel 1995
), but rendered inefficient to adapt the metrics because of cFN dysfunction (Robinson 1995
). From this perspective, it is interesting to note that in Robinson et al.'s (1993) experiment, the target systematically remained lit throughout all trials and a velocity reduction was observed. Although the reason why visual feedback apparently led to significant changes in gaze dynamics without notable changes in metrics remains obscure, these observations suggest that changes in gaze dynamics during cFN inactivation are not automatically associated with modifications in gaze dysmetria.
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ACKNOWLEDGEMENTS |
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We thank Dr. Rimas Kalesnykas for improving the quality of this paper. We also gratefully acknowledge N. Boyer-Zeller for providing essential support for histology and M. L. Loyalle for animal care.
This research was supported by Institut National de la Santé et de la Recherche Médicale U94 and by Human Frontier Science Program Grant RG-58/92B. L. Goffart was supported by a fellowship from the French Ministry of Research and Technology.
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FOOTNOTES |
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Present address of L. Goffart: Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
1
The observation made by Noda et al. (1990) in the monkey, that neurons in the fastigial oculomotor region (FOR) project only to the contralateral SC, contrasts with the other anatomic studies quoted above. One way to reconcile these findings would be to assume that in the monkey, fastigial neurons sending a projection to the contralateral SC are confined within a circumscribed zone of the cFN corresponding to the FOR and that some of the neurons lying outside this zone would project to the ipsilateral SC. However, this hypothesis is not supported by the following experimental data: first, Noda et al. (1990)
reported that a large wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injection involving the caudal two-thirds of the fastigial nucleus (FN) led to an anterograde labeling restricted to the contralateral SC similar to that resulting from smaller injections confined to the FOR; second, the data by May et al. (1990)
strongly suggest that retrogradely labeled fastigial neurons after HRP injections in the SC are located symetrically on both sides, in a cFN zone very similar to the FOR. Regarding the cat, there is a good agreement between studies using anterograde and/or retrograde labeling techniques in showing a bilateral projection of the cFN to the SC (Hirai et al. 1982
; Kawamura et al. 1982
; Roldan and Reinoso-Suarez 1981
; Sugimoto et al. 1982
). In summary, all studies agree on the fact that cFN neurons project to the contralateral SC and thus provide a neuroanatomic basis for a collicular involvement in the dysmetria of gaze saccades directed toward an inactivated cFN. A projection from the cFN to the ipsilateral SC also can be taken as a neuroanatomic substrate for a collicular involvement in the gaze contraversive dysmetria in the cat but the extention of this hypothesis to the monkey is uncertain and requires further anatomic studies.
Address for reprint requests: D. Pélisson, Espace et Action, INSERM U 94, 16 Ave. Doyen Lépine, 69500 Bron, France.
Received 18 February 1997; accepted in final form 8 December 1997.
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REFERENCES |
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