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Smooth pursuit initiation in young and elderly subjects
Yision Res. Vol. 33, No. 2, pp. 203-210,
1993
Printed in Great Britain. All rights reserved
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0042-6989/93 $5.00 + 0.00 1993 Pergamon Press Ltd
Smooth Pursuit Initiation in Young and Elderly Subjects MARK J. MORROW,*?
JAMES A. SHARPE*
Received 6 January 1992; in revised form 19 June 1992
Smooth pursuit initiation to step-ramp sthnuli was investigated in normal subjects, young and elderly. Older subjects had significant reductions in initial pursuit acceleration before saccades, and in post-saccadic and peak pursuit velocities. Aging impairs the open-loop performance of the pursuit system, possibly by decreasing sensitivity to retinal image motion or by limiting the conversion of visual motion signals into commands for smooth pursuit. Lower open-loop pursuit gain degrades steady-state, closed-loop smooth pursuit in senescence. Our elderly subjects also made less accurate saccades to moving targets, implying defective use of visual motion information by the saccadic system. Smooth pursuit Aging Pursuit initiation
Saccades
50-100msec after pursuit eye movements have been initiated (Newsome, Wurtz & Komatsu, 1988). Smooth pursuit adapts to changes in visual feedback conditions by altering its late response characteristics, but not its initiation. Carl and Gellmann (1986) altered the normal eye-stimulus feedback relationship by driving pursuit targets with a signal that was the sum of eye velocity and a desired retinal slip velocity; eye motion could not reduce retinal slip. After a period of adaptation to this condition, subjects changed their late pursuit responses, but initial pursuit acceleration remained the same. In addition to these adaptive inputs, the maintenance of smooth pursuit is facilitated by neural circuits that anticipate target trajectory (Lisberger, Evinger, Johanson & Fuchs, 1981). After a subject tracks one half-cycle of low frequency sinusoidal target motion, about 200 msec after the eyes begin to move, phase lag between eye and target motion is minimized (van den Berg, 1988). Pursuit initiation can also be influenced by prediction, since subjects can generate anticipatory low-velocity smooth eye movements before a target jumps (Kowler & Steinman, 198 1). Normal young subjects maintain higher smooth pursuit velocities than elderly subjects to targets moving in predictable waveforms (Sharpe & Sylvester, 1978; Spooner, Sakala & Baloh, 1980; Zackon & Sharpe, 1987). Limitations of smooth pursuit maintenance in older subjects can be explained by a combination of a lower steady-state, closed-loop gain of the pursuit system and reduced acceleration saturation limits; pursuit gain is reduced at all target frequencies compared to young subjects, but it is most limited for high frequency, high acceleration targets (Zackon & Sharpe, 1987). Lower pursuit velocities in the elderly might represent constraints on the processing of visual motion information that is used to initiate pursuit and adjust for
INTRODUCTION Smooth ocular pursuit maintains the image of a small, slowly moving object near the fovea by matching eye velocity to target velocity. Most studies have focused on the steady-state characteristics of the pursuit system, measuring the maintenance of smooth pursuit to predictable target movement. The initiation of smooth pursuit can be analyzed with step-ramp stimuli, in which targets jump away from a fixation position, then move at a constant velocity (Rashbass, 1961). In response to step-ramp stimuli, subjects often activate smooth pursuit eye movements before any saccades; this pre-saccadic pursuit has a latency of about 125 msec and begins as a smooth acceleration of the eyes (Tychsen & Lisberger, 1986). In the initial 120-135 msec period of eye acceleration, smooth pursuit behaves as an open-loop system, without feedback, since it responds only to target motion that occurred before the eyes started to move. After its open-loop phase, the pursuit system begins to act on updated stimulus motion information as smooth eye movement reduces retinal image motion (slip); this “closes the loop” of negative visual feedback. Extraretinal signals of eye motion are probably used to maintain smooth pursuit after retinal slip has been minimized by the initial eye acceleration (Young, 1971). This extraretinal smooth eye movement input would provide positive feedback that compensates for delays in the negative visual feedback loop, thereby stabilizing eye velocity near target velocity. In monkeys, pursuit motor feedback becomes available to cortical motion processing areas *Neuro-ophthalmology Unit, The Toronto Hospital Neurological Center, and the Playfair Neuroscience Unit, University of Toronto. tTo whom reprint requests should be addressed at: Department of Neurology, Room 2B-182, Olive View Medical Center, Sylmar,
CA 91342, U.S.A. 203
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retinal image slip that occurs during pursuit maintenance. Alternatively, imperfect use of eye motion feedback or of adaptive or predictive inputs could degrade pursuit maintenance in senescence without affecting the initiation of smooth pursuit. We measured horizontal smooth pursuit to unpredictable step-ramp targets in young and elderly normal subjects to determine effects of aging on visual motion processing. We also analyzed saccades in these subjects, since step-ramp testing reveals the use of visual motion inputs by the saccadic system (Gellman & Carl, 1991). METHODS Horizontal movements of one eye were recorded in eleven normal subjects, using a magnetic search coil method (CNC Engineering, Seattle, Wash.) (Collewijn, van der Mark & Jansen, 1975). We investigated six young subjects (mean age 3 1 yr, range 29-35 yr) and five elderly subjects (mean age 67 yr, range 60-76 yr). Participants were inexperienced in the step-ramp task. No subject had a history of neurologic or ophthalmologic disease and none took any anticonvulsant or sedativehypnotic medication. Elderly subjects were cognitively intact, as assessed by a brief neurologic examination of mental status, but formal neuropsychologic testing was not performed. All subjects had corrected visual acuity of 20130 or better and viewed the target with both eyes. We monitored head movements with a helmet-mounted search coil and supported subjects’ heads with an occipital rest. Subjects were instructed to keep their heads motionless in mid-position and we rejected any trials with inadvertent head motion.
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The stimulus was a laser spot rear-projected onto a featureless screen 1.24 m from the subject; it subtended 0.25 deg of visual angle and was about 4.5 log units brighter than the normal fovea1 threshold. The laboratory was dimly illuminated. Target motion was generated by computer-controlled displacements of a mirror galvanometer (General Scanning, Watertown, Mass.). Preceding each trial, subjects fixated the target at the center of the screen. After an unpredictable fixation time of 0.5-l .Oset, the target began a horizontal constant velocity ramp either directly from center (center-ramp stimulus), or immediately after it stepped horizontally away from center (step-ramp stimulus). For step-ramp stimuli, the ramp moved either in the same direction as the step, taking the target farther away from center (foveofugal stimulus), or opposite to the step, bringing the target toward center (foveopetal stimulus) (Fig. 1). Stimuli were presented in pseudorandom order. An optical shutter with a response time of 1.0 msec (A. W. Vincent, Rochester, N.Y.) eliminated a visible streak during target steps. Shutter closure was computercontrolled, coincided with the onset of the target step and lasted 4 msec. We tested 400 responses in each subject, using 20 trials each of 16 different step-ramp stimuli and 4 different center-ramp stimuli. Step-ramp combinations comprised 4 step amplitudes (4 and 8 deg to either side of center) and 4 ramp velocities (20 and 40deg/sec rightward and leftward), while center-ramp combinations used the same ramp velocities without a target step. Ramp duration was 1.Oset, except for 40 deg/sec foveofugal stimuli, which ran off the screen in < 1.Oset (minimum duration, 730 msec). We gave subjects frequent rest
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FIGURE I. Polygraph recordings of responses to step-ramp target motion, showing target position, eye position and smooth eye velocity. Gaps in eye velocity records occur where saccades have been removed. In all trials, eye velocity peaked within 406500 msec after ramp onset and declined in anticipation of ramp offset. (A) Initial smooth pursuit acceleration, without a corrective saccade. For 20 deg/sec targets, peak smooth eye velocity often overshot target velocity. (B, C, D) Responses with brief or absent pre-saccadic pursuit. In (B) and (C) post-saccadic pursuit velocity was high, comprising about half of peak pursuit velocity; there were brief pre-saccadic eye accelerations, and smooth eye movement acceleration continued during the initial saccade. In (D) the eyes began smooth acceleration as the saccade ended. R, right; L, left.
PURSUIT INITIATION
periods and verbal encouragement pursuit.
to maintain attentive
Data analysis
Eye and target position signals were digitized at 500 Hz and stored on magnetic tape for off-line analysis using an interactive computer program. Digitized eye position data were smoothed by a 40-point moving window averager, in order to maximize the number of measurable responses. The smoothing operation of the averager approximated a second-order low-pass filter with bandwidth of cl0 Hz. This blurred the onset of smooth pursuit, resulting in small decreases in measured pursuit eye acceleration and small increases in latency. After smoothing, eye position data were differentiated to yield an eye velocity signal. Saccades were then identified and smooth eye motion data occurring within 40msec of a saccade were removed from analysis. A computer terminal displayed results of each trial. Eye and target motion were also monitored on a rectilinear ink-jet polygraph (Elema-Schiinander, Stockholm). When the first eye movement of a trial was smooth pursuit initiation [Fig. l(A)], we measured the latency and acceleration of the response, according to the method of Carl and Gellman (1987). Baseline eye velocity and its standard deviation were computed from digitized data of the 80 msec interval before target movement. Beginning when pursuit eye velocity deviated from baseline eye velocity (near zero) by three standard deviations, a regression line was calculated from 60-100 msec of eye velocity data. Eye acceleration was determined by the slope of this velocity regression line. Smooth pursuit latency was identified at the intercept of the eye velocity regression line with baseline eye velocity. We did not include responses with latencies of under 60 msec in measuring initial pursuit, since they may have represented anticipatory responses. Anticipatory pursuit can occur even to unpredictable stimuli such as those we employed (Kowler & Steinman, 1981), but we recorded very few such responses. In most trials, < 60 msec of smooth eye acceleration occurred between the onset of target motion and the first ocular saccade [Fig. I(B-D)]. In these trials, the initial pursuit acceleration was too brief to quantify accurately. Instead, we measured smooth pursuit eye velocity over the 20 msec interval immediately after the initial saccade ended. Thus, an initial smooth pursuit response was measured for all trials, either as an early eye acceleration, or as post-saccadic pursuit velocity. For all trials, we measured peak smooth eye velocity. The eyes typically reached peak velocity within 40&500 msec after the target moved (Fig. 1). Peak eye velocity was maintained briefly, then the eyes decelerated in anticipation of stimulus offset. In trials with ~60 msec of pre-saccadic pursuit, we also quantified the initial saccade, recording its latency, amplitude, and position error, the difference between eye and target position at the end of the saccade. Data were analyzed with the SAS statistical program (Cary, N.C.), using Wilcoxon rank-sum tests. No data
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were omitted from analysis. Analysis of covariance (ANCOVA) was also used to take target motion variables into account. Because subjects’ rightward and leftward responses were generally symmetrical, we pooled data from both directions. RESULTS
In many trials, saccades occurred too early to allow measurement of pursuit acceleration. This was especially true for responses to foveofugal step-ramp targets, which evoked saccades with shorter latencies than center-ramp or foveopetal step-ramp targets. Quantifiable presaccadic pursuit occurred in response to only 4% of foveofugal step-ramps overall and some subjects made no measurable initial pursuit responses to these stimuli. In contrast, pursuit initiation was reliably observed with foveopetal step-ramps (59% of trials) and center-ramps (38% of trials). We did not include the sparse data for foveofugal targets in our analyses. For foveopetal targets, we occasionally noted brief, small accelerations toward the step of target position, preceding the larger, oppositely-directed acceleration toward the target ramp. These pursuit responses to target position may have signified misinterpretation of the target step as the initial ramp motion, through low-pass spatiotemporal filtering in the pursuit system (Carl & Gellmann, 1987); we did not analyze them, since they were too small to measure reliably. Lapses of subjects’ attention during step-ramp trials usually resulted in earlier, more frequent saccades, and reduced the number of measurable pre-saccadic pursuit responses. Elderly subjects made quantifiable presaccadic pursuit in 33% of trials, while young subjects did so in 3 1% of trials; this implied that the levels of attention and motivation were similar in the two groups. Despite this, elderly subjects had pre-saccadic smooth pursuit accelerations averaging 29% lower than those of young subjects (Fig. 2). Individual values were highly variable; differences between the elderly and young groups were largely explained by three young subjects who produced high accelerations [Fig. 2(B, D)]. Reductions in mean pre-saccadic pursuit acceleration in older subjects were similar for 20 deg/sec targets (33%) and 40 deg/sec targets (26%) (Table 1). Pre-saccadic pursuit acceleration increased with doubling of target speed from 20 to 40 deg/sec; this increase was proportionately greater in older subjects (29%) than in young subjects (17%), but was not significant in either group by Wilcoxon rank sum test, due to the high variability of data (Table 1). Pursuit acceleration latency was similar in both age groups and was unaffected by target speed (Table 1). In trials without measurable pre-saccadic eye acceleration, smooth pursuit immediately after the initial saccade usually had high velocities that comprised over half of peak smooth pursuit velocity (Table 1). High postsaccadic smooth eye movement velocities were achieved by smooth eye accelerations that took place during initial saccades [Fig. l(B, C)]. Occasionally, smooth
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pursuit acceleration did not begin until the end of the initial saccade [Fig. l(D)]. Examination of smooth eye velocity records (Fig. 1) showed that pursuit acceleration was independent of saccades; gaps caused by excision of saccades could be interpolated accurately with lines having slopes between those of the pre- and postsaccadic smooth eye movement segments. Post-saccadic smooth pursuit velocity averaged 26% lower in our elderly group than in our young group (Fig. 3), while peak smooth pursuit velocity averaged 24% lower (Fig. 4). Pursuit velocities were significantly lower in the elderly at each target velocity (Table 1). Peak eye velocities varied between individuals and data
from young and old subjects overlapped [Fig. 4(B, D)], as they did for initial pursuit acceleration. When compared to 20deg/sec ramps, 40 deg/sec ramps evoked significantly higher post-saccadic pursuit velocities in both age groups and higher peak pursuit velocities in the young group (P < 0.001, Wilcoxon rank sum test) (Table 1). Despite the higher smooth pursuit velocities elicited by doubling ramp speed, pursuit gain, expressed as peak pursuit velocity divided by target ramp velocity, fell as target speed increased. Pursuit gain approached unity for 20 deg/sec target ramps, averaging 0.90 in the elderly and 1.04 in the young; smooth eye velocity often overshot target velocity [Fig. l(A)]. In
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FIGURE 2. Pre-saccadic eye acceleration vs step amplitude in elderly (dotted lines) and young (solid lines) subjects. Positive step amplitudes indicate initial target motion toward the fovea (foveopetal step-ramps), while zero step amplitude reflects ramps beginning at the fovea without a target step (center-ramps). (A, B) 20 deg/sec target ramp speed. (C, D) 40 deg/sec target ramp speed. (A, C) Averaged data from six young and five elderly subjects. Error bars indicate 1 SE. Each point represents at least 56 values (range 56-163). (B, D) Individual values from each subject.
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TABLE 1. Smooth pursuit responses in eleven normal subjects Smooth pursuit acceleration (deg/sd f Young Elderly 20 deg[see Young
91.9 f 45.5* (353) 61.8 k 16.2 (322)
fdegiw)
134*40 (696) 133 f 35 (636)
19.1 f 6.w (1667) 14.1 + 5.2 (1331)
24.4 _+5.7t (2400) * 18.6 & 5.1 (2000)
137&-41 (353) 130+35 (322)
15.9 f 3.77 (827) 12.1 f 3.9 (667)
20.8 f 2.8f (1200) 17.9 * 3.3 (1000)
132&40 (343) 135 f 37 (314)
22.5 k 5.9t (840) 16.0 f 5.6 (664)
28.0 + 5.9t (1200) 19.3 f 6.6 (1000)
Post-saccadic pursuit velocity
ramps
Elderly 40 deg /set Young
99.7 f 52.1* (696) 70.3 & 22.9 (636)
Peak smooth pursuit velocity (degfs=)
Smooth pursuit latency (msec)
ramps
Elderly
107.9 f 58.5 (343) 79.5 f 26.0 (314)
Mean data 5 1 SD, calculated from means of 20 trial types in each subject (values in parentheses indicate number of data represented). Upper two rows compare averages of all trials in six young and five elderly normal subjects; lower rows compare responses at each target speed in each age group. *P < 0.05; $'P< 0.001, by Wilcoxon rank sum test, comparing young to elderly values.
contrast, for 40 deg/sec ramps, mean gain decreased to 0.48 in the elderly and 0.70 in the young and pursuit velocity never exceeded 40 de&see. Saccadic position error was 19% higher in older subjects than young subjects (Fig. 5). This age group difference was not significant by Wilcoxon rank sum test (P = 0.09), but reached significance when target variables were taken into account (P = 0.02 by ANCOVA). Saccadic latencies to step-ramps were longer in the elderly than in the young (Table 2). Subjects in both groups made less accurate saccades to 40 deg/sec ramps than 20 deg/sec ramps (P < 0.001, Wilcoxon rank sum test) (Fig. 5). Inaccurate saccades typically underestimated stimulus motion by overshooting foveopetal targets and undershooting foveofugal targets. Faster ramps evoked larger saccadic amplitudes in both groups (P < 0.01). DISCUSSION
In response to unpredictable step-ramp target motion, elderly subjects had lower pre-saccadic pursuit accelerations, post-saccadic pursuit velocities and peak pursuit velocities than young subjects. Our finding of diminished initial pursuit acceleration in older subjects indicates that aging degrades smooth pursuit in its first 100 msec, before retinal feedback, extraretinal eye motion feedback, or adaptation begin to influence pursuit performance. This decline in presaccadic eye acceleration signifies a reduction in the open-loop gain of the pursuit system, which can explain the lower closed-loop, steadystate pursuit gain observed in the elderly when they track targets with sinusoidal and triangular waveforms (Sharpe & Sylvester, 1978; Spooner et al., 1980; Zackon & Sharpe, 1987). Decreased post-saccadic pursuit velocity in older subjects further demonstrates an agerelated decline in the initial motor output of pursuit,
although post-saccadic pursuit represents a later portion of the response than initial eye acceleration. Smooth pursuit is driven by visual motion information that is extracted from the relatively simple responses of retinal photoreceptors. Current models incorporate two parallel channels for visual processing, one primarily concerned with motion and spatial features, the other with form and color. In monkeys, the pathway for motion analysis includes retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nuclei (Schiller & Logothetis, 1990). 30 -
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FIGURE 3. Initial post-saccadic pursuit eye velocity vs step amplitude in elderly and young subjects. Same conventions as Fig. 2(A, C); negative step amplitudes signify initial target motion away from the fovea (foveofugal step-ramps). Each point represents at least 48 values (range 48-236).
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Signals from this magnocellular, or broad-band, retinogeniculate channel reach cerebral cortical regions with directionally-selective neurons, including the middle temporal (MT) and middle superior temporal (MST) areas (Maunsell & Van Essen, 1983; Newsome, Wurtz, Diirsteler & Mikami, 1988). Corticofugal pathways originating in these areas terminate in brainstem nuclei that project to the cerebellum (Tusa & Ungerleider, 1988). Impaired pursuit initiation in elderly subjects could be caused by senescent degradation of afferent visual motion inputs. Normal elderly subjects have been shown to have subtle reductions in several visual
and JAMES
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functions, including visual acuity, visual fields and contrast sensitivity, compared to young subjects (Drance, Berry & Hughes, 1967; Owsley, Sekuler & Siemsen, 1983). Causes of this generalized visual decline in aging include diminished photoreceptor function and loss of retinal ganglion cell axons and striate and peristriate cortical neurons (Brody, 1955; Balazsi, Rootman, Drance, Sehulzer & Douglas, 1984; Bagolini, Porciatti, Falsini, Scalia, Neroni & Moretti, 1988). Alzheimer’s disease, which is characterized by dropout of cerebral cortical neurons and large retinal ganglion
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FIGURE 4. Peak smooth pursuit velocity vs step amplitude in elderly and young subjects. Same conventions as previous figures. (A, B) 20 deg/sec target ramp speed. (C, D) 40 deg/sec target ramp speed. (A, C) Averaged data from six young and five elderly subjects. Error bars indicate 1 SE. Each point represents either 200 (older subjects) or 240 (young subjects) values. (8, D) Individual values from each subject.
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cell axons (Brun & Englund, 198 1; Sadun & Bassi, 1990), impairs smooth pursuit maintenance (Fletcher & Sharpe, 1988). Damage to peristriate cortical regions like areas MT and MST in monkeys impairs smooth pursuit initiation and maintenance (Dtirsteler & Wurtz, 1988). Mild cognitive impairment in our elderly subjects cannot be excluded as a contributor to their poorer performance, but mental status appeared to be intact in these subjects. Moreover, motivation, as estimated by the frequency of measurable pre-saccadic pursuit responses, was equal in our young and elderly groups. Degraded conversion of visual sensory inputs into motor commands might also explain the senescent decline we recorded in ocular responses to moving stimuli. Cerebellar Purkinje cells in the flocculus and posterior vermis act as a sensory-motor interface for pursuit by constructing a neural representation of target motion in space (Suzuki & Keller, 1988). This target motion signal is probably used as a pursuit motor command. Senile loss of Purkinje cells (Hall, Miller & Corsellis, 1975) could contribute to diminished smooth pursuit function. Senescent changes in dopaminergic nigrostriatal pathways (McGeer, McGeer & Suzuki, 1977) could also account for some impairment of visually guided eye movements. Degeneration of nigrostriatal pathways in Parkinson’s disease is associated with impaired smooth pursuit and saccades (White, Saint-Cyr, Tomlinson & Sharpe, 1983). Degraded smooth pursuit in the elderly does not result from degeneration of the ocular motor nuclei, since they are spared in senescence (Vijayashankar & Brody, 1977). The outputs of the pursuit and saccadic systems appeared to be independent during step-ramp tracking. We found no evidence of latency interaction between smooth pursuit and saccades; a sustained smooth pursuit
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acceleration usually preceded saccades when target ramps moved toward fixation, but not when they moved away from fixation. Moreover, smooth eye velocity traces showed no effect of saccades. Although its motor output is independent of pursuit, the saccadic system, like the pursuit system, receives visual motion information. The accuracy of saccades to step-ramp stimuli is best explained by the use of target velocity inputs (Gellmann & Carl, 1991). Damage to cortical motion processing areas in monkeys and humans causes inaccurate saccades to moving, but not stationary, targets, implying selective disruption of target motion inputs (Newsome et al., 1985; Thurston, Leigh, Crawford, Thompson & Kennard, 1988). The impairment of saccadic accuracy we observed in older subjects could arise from a deficit in visual motion inputs to the saccadic system. However, elderly subjects also make less accurate saccades to stationary targets (Sharpe & Zackon, 1987), demonstrating impairment of saccadic control independent of visual motion. We found that normal elderly subjects have prolonged latency of saccades to moving targets, as they do for saccades to stationary targets (Sharpe & Zackon, 1987). In our subjects, pursuit acceleration, post-saccadic pursuit velocity, peak pursuit velocity and saccadic amplitude all increased when target speed doubled, but these measures did not rise in proportion to target speed. Smooth pursuit gain fell and saccadic error rose for 40 deg/sec targets compared with 20 deg/sec targets. These findings suggest sensory limitations of target motion signals used by the smooth pursuit and saccadic systems. The population of neurons in cortical area MT in monkeys is most sensitive to retinal slip speeds between 8 and 64 deglsec, although some individual neurons have preferred speeds up to 256 deg/sec (Maunsell & Van Essen, 1983). This speed-selectivity of neurons parallels the relationship between pursuit
TABLE 2. Saccade responses in eleven normals
Saccade latency (msec)
Saccade amplitude (deg)
Position error (de&
1667 1331
206 f 76* 224 * 74
6.35 & 3.50 6.27 + 3.68
1.59 k 1.30 1.90 rt 1.43
20 deg jsec ramps Young Elderly
827 667
211 +81* 238 f 86
5.52 ;t 3.22 5.36 + 3.39
0.83 + 0.76 1.06 + 0.84
40 deg}sec ramps Young Elderly
840 664
201&71 209 & 57
7.19 + 3.61 7.18 + 3.78
2.39 + 1.28 2.74 + 1.40
N Young Elderly
Mean data rfr 1 SD, calculated from means of 20 trial types in each subject. N column signifies number of data represented in adjacent row. Upper two rows compare averages of at1 trials in six young and five elderly normal subjects; lower rows compare responses at each target speed in each age group. *P < 0.05 by Wilcoxon rank sum test, comparing young to elderly values. The age group difference in saccadic position error did not reach significance by Wilcoxon rank sum test (P = 0.09), but did so with ANCOVA (P = 0.02).
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initiation and target velocity in monkeys (Lisberger & Westbrook, 1985); pursuit eye acceleration rises very slowly or falls when target velocity exceeds 45 deg/sec. Our findings indicate that humans do not generate accurate ocular motor responses when retinal slip speeds approach 40 deg/sec. Steady-state smooth pursuit can reach higher velocities than the peak velocities we recorded to brief, unpredictable ramp targets by gradually reducing retinal slip with smooth eye acceleration. Thus, pursuit velocity in normal humans can reach 150 deg/sec for sine wave targets (Lisberger et al., 198 1); target predictability contributes to this high velocity of pursuit maintenance. REFERENCES Bagolini, B., Porciatti, V., Falsini, B., Scalia, G., Neroni, M. & Moretti, G. (1988). Macular electroretinogram as a function of age of subjects. Documenra Ophthalmologica, 70, 3743. Balazsi, A. G., Rootman, J., Drance, S. M., Schulzer, M. & Douglas, G. R. (1984). The effect of age on the nerve fiber population of the human optic nerve. American Journal of Ophthalmology, 97. 760-766. van den Berg, A. V. (1988). Human smooth pursuit during transient perturbations of predictable and unpredictable target movement. Experimental Brain Research, 72, 95-108. Brody, H. (1955). Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. Journal of Comparative Neurology, 102, 511-556. Brun, A. & Englund, E. (1981). Regional pattern of degeneration in Alzheimer’s disease: Neuronal loss and histopathological grading. Histopathology, 5, 549-564. Carl, J. R. & Gellmann, R. S. (1986). Adaptive responses in human smooth pursuit. In Keller, E. L. & Zee, D. S. (Eds), Adaptive processes in visual and oculomotor systems (pp. 335-339). Oxford: Pergamon Press. Carl, J. R. & Gellmann, R. S. (1987). Human smooth pursuit: Stimulus-dependent responses. Journal of Neurophysiology, 57, 14461463. Collewijn, H., Van der Mark, F. & Jansen, T. C. (1975). Precise recording of human eye movements. Vision Research, 15, 447450. Drance, S. M., Berry, V. & Hughes, A. (1967). The effects of age on the central isopter of the normal visual field. Canadian Journal of Ophthalmology, 2, 79982. Diirsteler, M. R. & Wurtz, R. H. (1988). Pursuit and optokinetic defects following chemical lesions of cortical areas MT and MST. Journal of Neurophysiology, 60, 9W965. Fletcher, W. A. & Sharpe, J. A. (1988). Smooth pursuit dysfunction in Alzheimer’s disease. Neurology, 38, 272--277. Gellman, R. S. & Carl, J. R. (1991). Motion processing for saccadic eye movements in humans. Experimental Brain Research, 84, 660667. Hall, T. C., Miller, A. K. H. & Corsellis, J. A. N. (1975). Variations in the human Purkinje cell population according to age and sex. Neuropathology and Applied Neurobiology, I, 267-292. Kowler, E. & Steinman, R. S. (1981). The effect ofexpectations on slow oculomotor control-III. Guessing unpredictable target displacements. Vision Research, 21, 191-203. Lisberger, S. G. & Westbrook, L. E. (1985). Properties of visual inputs that initiate horizontal smooth pursuit eye movements in monkeys. Journal of Neuroscience, 5, 166221673. Lisberger, S. G., Evinger, C., Johanson, G. W. & Fuchs, A. F. (1981). Relationship between eye acceleration and retina1 image velocity
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during fovea1 smooth pursuit in man and monkey. Journal of Neurophysiology, 46, 2299249. Maunsell, J. H. R. & Van Essen, D. C. (1983). Functional properties of neurons in middle temporal visual area of the macaque monkey. I. Selectivity for stimulus direction, speed, and orientation. Journal of Neurophysiology, 49, 112771147. McGeer, P. L., McGeer, E. G. & Suzuki, J. S. (1977). Aging and extrapyramidal function. Archives of Neurology, 34, 3333.5. Newsome, W. T., Wurtz, R. H. & Komatsu, H. (1988). Relation of cortical areas MT and MST to pursuit eye movements, II. Differentiation of retinal from extraretinal inputs. Journal of Neurophysiology, 60, 604620. Newsome, W. T., Wurtz, R. H., Dtirsteler, M. R. & Mikami, A. (1985). Deficits in visual motion processing following ibotenic acid lesions of the middle temporal visual area of the macaque monkey. Journal of Neuroscience, 5, 8255840. Owsley, C.. Sekuler, R. Jr Siemsen, D. (1983). Contrast sensitivity throughout adulthood. Vision Research, 23, 6899699. Rashbass, C. (1961). The relationship between saccadic and smooth tracking eye movements. Journal of Physiology, 159, 326338. Sadun, A. A. & Bassi, C. J. (1990). Optic nerve damage in Alzheimer’s disease. Ophthalmology, 97, 9- I I. Schiller, P. H. & Logothetis, N. K. (1990). The color-opponent and broad-band channels of the primate visual system. Trends in Neurosciences, 13, 3922398. Sharpe, J. A. & Sylvester, T. 0. (1978). Effects of aging on horizontal smooth pursuit. Investigative Ophthalmology and Visual Science, 17, 465468. Sharpe, J. A. & Zackon, D. H. (1987). Senescent saccades. Effects of aging on their accuracy, latency and velocity. Acta Otolaryngologica, 104, 422428. Spooner, J. W., Sakala, S. M. & Baloh, R. W. (1980). Effect of aging on eye tracking. Archives of Neurology, 37, 5755576. Suzuki, D. A. & Keller, E. L. (I 988). The role of the posterior vermis of monkey cerebellum in smooth-pursuit eye movement control. II. Target velocity-related Purkinje cell activity. Journal of Neurophysiology, 59, 1940. Thurston, S. E., Leigh, R. J.. Crawford, T., Thompson, A. & Kennard. C. (1988). Two distinct deficits of visual tracking caused by unilateral lesions of cerebral cortex in humans. Annals of Neurology, 23, 266-273. Tusa, R. J. & Ungerleider, L. G. (1988). Fiber pathways of cortical areas mediating smooth pursuit eye movements in monkeys. Annals of Neurology, 23, 1744183. Tychsen, L. & Lisberger, S. G. (1986). Visual motion processing for the initiation of smooth-pursuit eye movements in humans. Journal of Neurophysiology, 56, 953-968. Vijayashankar, N. & Brody, H. (1977). A study of aging in the human abducens nucleus. Journal ofComparative Neurology, 173,433438. White, 0. B., Saint-Cyr, J. A., Tomlinson, R. D. & Sharpe, J. A. (1983). Ocular motor deficits in Parkinson’s disease. II. Control of the saccadic and smooth pursuit systems. Brain, 106, 571.-587. Young, L. R. (1971). Pursuit eye tracking movements. In Bach-yRita, P. & Collins, C. C. (Eds), The control of eye movements (pp. 4299443). New York: Academic Press. Zackon, D. H. & Sharpe, J. A. (1987). Smooth pursuit in senescence. Effects of target acceleration and velocity. Acfa Otolaryngologica, 104, 290-297.
Acknowledgements-This research was supported by NIH Grant EY-06040, a Chisholm Memorial Scholarship, and The Toronto Hospital (Dr Morrow) and MRC of Canada Grants MT-5404 and ME-4509 (Dr Sharpe). We thank Phat Nguyen and Dr Janine Johnston for technical assistance.
1993
Printed in Great Britain. All rights reserved
CopYright
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0042-6989/93 $5.00 + 0.00 1993 Pergamon Press Ltd
Smooth Pursuit Initiation in Young and Elderly Subjects MARK J. MORROW,*?
JAMES A. SHARPE*
Received 6 January 1992; in revised form 19 June 1992
Smooth pursuit initiation to step-ramp sthnuli was investigated in normal subjects, young and elderly. Older subjects had significant reductions in initial pursuit acceleration before saccades, and in post-saccadic and peak pursuit velocities. Aging impairs the open-loop performance of the pursuit system, possibly by decreasing sensitivity to retinal image motion or by limiting the conversion of visual motion signals into commands for smooth pursuit. Lower open-loop pursuit gain degrades steady-state, closed-loop smooth pursuit in senescence. Our elderly subjects also made less accurate saccades to moving targets, implying defective use of visual motion information by the saccadic system. Smooth pursuit Aging Pursuit initiation
Saccades
50-100msec after pursuit eye movements have been initiated (Newsome, Wurtz & Komatsu, 1988). Smooth pursuit adapts to changes in visual feedback conditions by altering its late response characteristics, but not its initiation. Carl and Gellmann (1986) altered the normal eye-stimulus feedback relationship by driving pursuit targets with a signal that was the sum of eye velocity and a desired retinal slip velocity; eye motion could not reduce retinal slip. After a period of adaptation to this condition, subjects changed their late pursuit responses, but initial pursuit acceleration remained the same. In addition to these adaptive inputs, the maintenance of smooth pursuit is facilitated by neural circuits that anticipate target trajectory (Lisberger, Evinger, Johanson & Fuchs, 1981). After a subject tracks one half-cycle of low frequency sinusoidal target motion, about 200 msec after the eyes begin to move, phase lag between eye and target motion is minimized (van den Berg, 1988). Pursuit initiation can also be influenced by prediction, since subjects can generate anticipatory low-velocity smooth eye movements before a target jumps (Kowler & Steinman, 198 1). Normal young subjects maintain higher smooth pursuit velocities than elderly subjects to targets moving in predictable waveforms (Sharpe & Sylvester, 1978; Spooner, Sakala & Baloh, 1980; Zackon & Sharpe, 1987). Limitations of smooth pursuit maintenance in older subjects can be explained by a combination of a lower steady-state, closed-loop gain of the pursuit system and reduced acceleration saturation limits; pursuit gain is reduced at all target frequencies compared to young subjects, but it is most limited for high frequency, high acceleration targets (Zackon & Sharpe, 1987). Lower pursuit velocities in the elderly might represent constraints on the processing of visual motion information that is used to initiate pursuit and adjust for
INTRODUCTION Smooth ocular pursuit maintains the image of a small, slowly moving object near the fovea by matching eye velocity to target velocity. Most studies have focused on the steady-state characteristics of the pursuit system, measuring the maintenance of smooth pursuit to predictable target movement. The initiation of smooth pursuit can be analyzed with step-ramp stimuli, in which targets jump away from a fixation position, then move at a constant velocity (Rashbass, 1961). In response to step-ramp stimuli, subjects often activate smooth pursuit eye movements before any saccades; this pre-saccadic pursuit has a latency of about 125 msec and begins as a smooth acceleration of the eyes (Tychsen & Lisberger, 1986). In the initial 120-135 msec period of eye acceleration, smooth pursuit behaves as an open-loop system, without feedback, since it responds only to target motion that occurred before the eyes started to move. After its open-loop phase, the pursuit system begins to act on updated stimulus motion information as smooth eye movement reduces retinal image motion (slip); this “closes the loop” of negative visual feedback. Extraretinal signals of eye motion are probably used to maintain smooth pursuit after retinal slip has been minimized by the initial eye acceleration (Young, 1971). This extraretinal smooth eye movement input would provide positive feedback that compensates for delays in the negative visual feedback loop, thereby stabilizing eye velocity near target velocity. In monkeys, pursuit motor feedback becomes available to cortical motion processing areas *Neuro-ophthalmology Unit, The Toronto Hospital Neurological Center, and the Playfair Neuroscience Unit, University of Toronto. tTo whom reprint requests should be addressed at: Department of Neurology, Room 2B-182, Olive View Medical Center, Sylmar,
CA 91342, U.S.A. 203
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retinal image slip that occurs during pursuit maintenance. Alternatively, imperfect use of eye motion feedback or of adaptive or predictive inputs could degrade pursuit maintenance in senescence without affecting the initiation of smooth pursuit. We measured horizontal smooth pursuit to unpredictable step-ramp targets in young and elderly normal subjects to determine effects of aging on visual motion processing. We also analyzed saccades in these subjects, since step-ramp testing reveals the use of visual motion inputs by the saccadic system (Gellman & Carl, 1991). METHODS Horizontal movements of one eye were recorded in eleven normal subjects, using a magnetic search coil method (CNC Engineering, Seattle, Wash.) (Collewijn, van der Mark & Jansen, 1975). We investigated six young subjects (mean age 3 1 yr, range 29-35 yr) and five elderly subjects (mean age 67 yr, range 60-76 yr). Participants were inexperienced in the step-ramp task. No subject had a history of neurologic or ophthalmologic disease and none took any anticonvulsant or sedativehypnotic medication. Elderly subjects were cognitively intact, as assessed by a brief neurologic examination of mental status, but formal neuropsychologic testing was not performed. All subjects had corrected visual acuity of 20130 or better and viewed the target with both eyes. We monitored head movements with a helmet-mounted search coil and supported subjects’ heads with an occipital rest. Subjects were instructed to keep their heads motionless in mid-position and we rejected any trials with inadvertent head motion.
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The stimulus was a laser spot rear-projected onto a featureless screen 1.24 m from the subject; it subtended 0.25 deg of visual angle and was about 4.5 log units brighter than the normal fovea1 threshold. The laboratory was dimly illuminated. Target motion was generated by computer-controlled displacements of a mirror galvanometer (General Scanning, Watertown, Mass.). Preceding each trial, subjects fixated the target at the center of the screen. After an unpredictable fixation time of 0.5-l .Oset, the target began a horizontal constant velocity ramp either directly from center (center-ramp stimulus), or immediately after it stepped horizontally away from center (step-ramp stimulus). For step-ramp stimuli, the ramp moved either in the same direction as the step, taking the target farther away from center (foveofugal stimulus), or opposite to the step, bringing the target toward center (foveopetal stimulus) (Fig. 1). Stimuli were presented in pseudorandom order. An optical shutter with a response time of 1.0 msec (A. W. Vincent, Rochester, N.Y.) eliminated a visible streak during target steps. Shutter closure was computercontrolled, coincided with the onset of the target step and lasted 4 msec. We tested 400 responses in each subject, using 20 trials each of 16 different step-ramp stimuli and 4 different center-ramp stimuli. Step-ramp combinations comprised 4 step amplitudes (4 and 8 deg to either side of center) and 4 ramp velocities (20 and 40deg/sec rightward and leftward), while center-ramp combinations used the same ramp velocities without a target step. Ramp duration was 1.Oset, except for 40 deg/sec foveofugal stimuli, which ran off the screen in < 1.Oset (minimum duration, 730 msec). We gave subjects frequent rest
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FIGURE I. Polygraph recordings of responses to step-ramp target motion, showing target position, eye position and smooth eye velocity. Gaps in eye velocity records occur where saccades have been removed. In all trials, eye velocity peaked within 406500 msec after ramp onset and declined in anticipation of ramp offset. (A) Initial smooth pursuit acceleration, without a corrective saccade. For 20 deg/sec targets, peak smooth eye velocity often overshot target velocity. (B, C, D) Responses with brief or absent pre-saccadic pursuit. In (B) and (C) post-saccadic pursuit velocity was high, comprising about half of peak pursuit velocity; there were brief pre-saccadic eye accelerations, and smooth eye movement acceleration continued during the initial saccade. In (D) the eyes began smooth acceleration as the saccade ended. R, right; L, left.
PURSUIT INITIATION
periods and verbal encouragement pursuit.
to maintain attentive
Data analysis
Eye and target position signals were digitized at 500 Hz and stored on magnetic tape for off-line analysis using an interactive computer program. Digitized eye position data were smoothed by a 40-point moving window averager, in order to maximize the number of measurable responses. The smoothing operation of the averager approximated a second-order low-pass filter with bandwidth of cl0 Hz. This blurred the onset of smooth pursuit, resulting in small decreases in measured pursuit eye acceleration and small increases in latency. After smoothing, eye position data were differentiated to yield an eye velocity signal. Saccades were then identified and smooth eye motion data occurring within 40msec of a saccade were removed from analysis. A computer terminal displayed results of each trial. Eye and target motion were also monitored on a rectilinear ink-jet polygraph (Elema-Schiinander, Stockholm). When the first eye movement of a trial was smooth pursuit initiation [Fig. l(A)], we measured the latency and acceleration of the response, according to the method of Carl and Gellman (1987). Baseline eye velocity and its standard deviation were computed from digitized data of the 80 msec interval before target movement. Beginning when pursuit eye velocity deviated from baseline eye velocity (near zero) by three standard deviations, a regression line was calculated from 60-100 msec of eye velocity data. Eye acceleration was determined by the slope of this velocity regression line. Smooth pursuit latency was identified at the intercept of the eye velocity regression line with baseline eye velocity. We did not include responses with latencies of under 60 msec in measuring initial pursuit, since they may have represented anticipatory responses. Anticipatory pursuit can occur even to unpredictable stimuli such as those we employed (Kowler & Steinman, 1981), but we recorded very few such responses. In most trials, < 60 msec of smooth eye acceleration occurred between the onset of target motion and the first ocular saccade [Fig. I(B-D)]. In these trials, the initial pursuit acceleration was too brief to quantify accurately. Instead, we measured smooth pursuit eye velocity over the 20 msec interval immediately after the initial saccade ended. Thus, an initial smooth pursuit response was measured for all trials, either as an early eye acceleration, or as post-saccadic pursuit velocity. For all trials, we measured peak smooth eye velocity. The eyes typically reached peak velocity within 40&500 msec after the target moved (Fig. 1). Peak eye velocity was maintained briefly, then the eyes decelerated in anticipation of stimulus offset. In trials with ~60 msec of pre-saccadic pursuit, we also quantified the initial saccade, recording its latency, amplitude, and position error, the difference between eye and target position at the end of the saccade. Data were analyzed with the SAS statistical program (Cary, N.C.), using Wilcoxon rank-sum tests. No data
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were omitted from analysis. Analysis of covariance (ANCOVA) was also used to take target motion variables into account. Because subjects’ rightward and leftward responses were generally symmetrical, we pooled data from both directions. RESULTS
In many trials, saccades occurred too early to allow measurement of pursuit acceleration. This was especially true for responses to foveofugal step-ramp targets, which evoked saccades with shorter latencies than center-ramp or foveopetal step-ramp targets. Quantifiable presaccadic pursuit occurred in response to only 4% of foveofugal step-ramps overall and some subjects made no measurable initial pursuit responses to these stimuli. In contrast, pursuit initiation was reliably observed with foveopetal step-ramps (59% of trials) and center-ramps (38% of trials). We did not include the sparse data for foveofugal targets in our analyses. For foveopetal targets, we occasionally noted brief, small accelerations toward the step of target position, preceding the larger, oppositely-directed acceleration toward the target ramp. These pursuit responses to target position may have signified misinterpretation of the target step as the initial ramp motion, through low-pass spatiotemporal filtering in the pursuit system (Carl & Gellmann, 1987); we did not analyze them, since they were too small to measure reliably. Lapses of subjects’ attention during step-ramp trials usually resulted in earlier, more frequent saccades, and reduced the number of measurable pre-saccadic pursuit responses. Elderly subjects made quantifiable presaccadic pursuit in 33% of trials, while young subjects did so in 3 1% of trials; this implied that the levels of attention and motivation were similar in the two groups. Despite this, elderly subjects had pre-saccadic smooth pursuit accelerations averaging 29% lower than those of young subjects (Fig. 2). Individual values were highly variable; differences between the elderly and young groups were largely explained by three young subjects who produced high accelerations [Fig. 2(B, D)]. Reductions in mean pre-saccadic pursuit acceleration in older subjects were similar for 20 deg/sec targets (33%) and 40 deg/sec targets (26%) (Table 1). Pre-saccadic pursuit acceleration increased with doubling of target speed from 20 to 40 deg/sec; this increase was proportionately greater in older subjects (29%) than in young subjects (17%), but was not significant in either group by Wilcoxon rank sum test, due to the high variability of data (Table 1). Pursuit acceleration latency was similar in both age groups and was unaffected by target speed (Table 1). In trials without measurable pre-saccadic eye acceleration, smooth pursuit immediately after the initial saccade usually had high velocities that comprised over half of peak smooth pursuit velocity (Table 1). High postsaccadic smooth eye movement velocities were achieved by smooth eye accelerations that took place during initial saccades [Fig. l(B, C)]. Occasionally, smooth
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pursuit acceleration did not begin until the end of the initial saccade [Fig. l(D)]. Examination of smooth eye velocity records (Fig. 1) showed that pursuit acceleration was independent of saccades; gaps caused by excision of saccades could be interpolated accurately with lines having slopes between those of the pre- and postsaccadic smooth eye movement segments. Post-saccadic smooth pursuit velocity averaged 26% lower in our elderly group than in our young group (Fig. 3), while peak smooth pursuit velocity averaged 24% lower (Fig. 4). Pursuit velocities were significantly lower in the elderly at each target velocity (Table 1). Peak eye velocities varied between individuals and data
from young and old subjects overlapped [Fig. 4(B, D)], as they did for initial pursuit acceleration. When compared to 20deg/sec ramps, 40 deg/sec ramps evoked significantly higher post-saccadic pursuit velocities in both age groups and higher peak pursuit velocities in the young group (P < 0.001, Wilcoxon rank sum test) (Table 1). Despite the higher smooth pursuit velocities elicited by doubling ramp speed, pursuit gain, expressed as peak pursuit velocity divided by target ramp velocity, fell as target speed increased. Pursuit gain approached unity for 20 deg/sec target ramps, averaging 0.90 in the elderly and 1.04 in the young; smooth eye velocity often overshot target velocity [Fig. l(A)]. In
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FIGURE 2. Pre-saccadic eye acceleration vs step amplitude in elderly (dotted lines) and young (solid lines) subjects. Positive step amplitudes indicate initial target motion toward the fovea (foveopetal step-ramps), while zero step amplitude reflects ramps beginning at the fovea without a target step (center-ramps). (A, B) 20 deg/sec target ramp speed. (C, D) 40 deg/sec target ramp speed. (A, C) Averaged data from six young and five elderly subjects. Error bars indicate 1 SE. Each point represents at least 56 values (range 56-163). (B, D) Individual values from each subject.
PURSUIT INITIATION
IN AGING
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TABLE 1. Smooth pursuit responses in eleven normal subjects Smooth pursuit acceleration (deg/sd f Young Elderly 20 deg[see Young
91.9 f 45.5* (353) 61.8 k 16.2 (322)
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134*40 (696) 133 f 35 (636)
19.1 f 6.w (1667) 14.1 + 5.2 (1331)
24.4 _+5.7t (2400) * 18.6 & 5.1 (2000)
137&-41 (353) 130+35 (322)
15.9 f 3.77 (827) 12.1 f 3.9 (667)
20.8 f 2.8f (1200) 17.9 * 3.3 (1000)
132&40 (343) 135 f 37 (314)
22.5 k 5.9t (840) 16.0 f 5.6 (664)
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99.7 f 52.1* (696) 70.3 & 22.9 (636)
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107.9 f 58.5 (343) 79.5 f 26.0 (314)
Mean data 5 1 SD, calculated from means of 20 trial types in each subject (values in parentheses indicate number of data represented). Upper two rows compare averages of all trials in six young and five elderly normal subjects; lower rows compare responses at each target speed in each age group. *P < 0.05; $'P< 0.001, by Wilcoxon rank sum test, comparing young to elderly values.
contrast, for 40 deg/sec ramps, mean gain decreased to 0.48 in the elderly and 0.70 in the young and pursuit velocity never exceeded 40 de&see. Saccadic position error was 19% higher in older subjects than young subjects (Fig. 5). This age group difference was not significant by Wilcoxon rank sum test (P = 0.09), but reached significance when target variables were taken into account (P = 0.02 by ANCOVA). Saccadic latencies to step-ramps were longer in the elderly than in the young (Table 2). Subjects in both groups made less accurate saccades to 40 deg/sec ramps than 20 deg/sec ramps (P < 0.001, Wilcoxon rank sum test) (Fig. 5). Inaccurate saccades typically underestimated stimulus motion by overshooting foveopetal targets and undershooting foveofugal targets. Faster ramps evoked larger saccadic amplitudes in both groups (P < 0.01). DISCUSSION
In response to unpredictable step-ramp target motion, elderly subjects had lower pre-saccadic pursuit accelerations, post-saccadic pursuit velocities and peak pursuit velocities than young subjects. Our finding of diminished initial pursuit acceleration in older subjects indicates that aging degrades smooth pursuit in its first 100 msec, before retinal feedback, extraretinal eye motion feedback, or adaptation begin to influence pursuit performance. This decline in presaccadic eye acceleration signifies a reduction in the open-loop gain of the pursuit system, which can explain the lower closed-loop, steadystate pursuit gain observed in the elderly when they track targets with sinusoidal and triangular waveforms (Sharpe & Sylvester, 1978; Spooner et al., 1980; Zackon & Sharpe, 1987). Decreased post-saccadic pursuit velocity in older subjects further demonstrates an agerelated decline in the initial motor output of pursuit,
although post-saccadic pursuit represents a later portion of the response than initial eye acceleration. Smooth pursuit is driven by visual motion information that is extracted from the relatively simple responses of retinal photoreceptors. Current models incorporate two parallel channels for visual processing, one primarily concerned with motion and spatial features, the other with form and color. In monkeys, the pathway for motion analysis includes retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nuclei (Schiller & Logothetis, 1990). 30 -
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FIGURE 3. Initial post-saccadic pursuit eye velocity vs step amplitude in elderly and young subjects. Same conventions as Fig. 2(A, C); negative step amplitudes signify initial target motion away from the fovea (foveofugal step-ramps). Each point represents at least 48 values (range 48-236).
MARK
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Signals from this magnocellular, or broad-band, retinogeniculate channel reach cerebral cortical regions with directionally-selective neurons, including the middle temporal (MT) and middle superior temporal (MST) areas (Maunsell & Van Essen, 1983; Newsome, Wurtz, Diirsteler & Mikami, 1988). Corticofugal pathways originating in these areas terminate in brainstem nuclei that project to the cerebellum (Tusa & Ungerleider, 1988). Impaired pursuit initiation in elderly subjects could be caused by senescent degradation of afferent visual motion inputs. Normal elderly subjects have been shown to have subtle reductions in several visual
and JAMES
A. SHARPE
functions, including visual acuity, visual fields and contrast sensitivity, compared to young subjects (Drance, Berry & Hughes, 1967; Owsley, Sekuler & Siemsen, 1983). Causes of this generalized visual decline in aging include diminished photoreceptor function and loss of retinal ganglion cell axons and striate and peristriate cortical neurons (Brody, 1955; Balazsi, Rootman, Drance, Sehulzer & Douglas, 1984; Bagolini, Porciatti, Falsini, Scalia, Neroni & Moretti, 1988). Alzheimer’s disease, which is characterized by dropout of cerebral cortical neurons and large retinal ganglion
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0
4
8
Step FIGURE
amplitude
(deg)
5. Saccadic position error vs step amplitude in elderly and
young subjects. Same conventions as previous figures. Each point represents at least 48 values (range 48-236).
cell axons (Brun & Englund, 198 1; Sadun & Bassi, 1990), impairs smooth pursuit maintenance (Fletcher & Sharpe, 1988). Damage to peristriate cortical regions like areas MT and MST in monkeys impairs smooth pursuit initiation and maintenance (Dtirsteler & Wurtz, 1988). Mild cognitive impairment in our elderly subjects cannot be excluded as a contributor to their poorer performance, but mental status appeared to be intact in these subjects. Moreover, motivation, as estimated by the frequency of measurable pre-saccadic pursuit responses, was equal in our young and elderly groups. Degraded conversion of visual sensory inputs into motor commands might also explain the senescent decline we recorded in ocular responses to moving stimuli. Cerebellar Purkinje cells in the flocculus and posterior vermis act as a sensory-motor interface for pursuit by constructing a neural representation of target motion in space (Suzuki & Keller, 1988). This target motion signal is probably used as a pursuit motor command. Senile loss of Purkinje cells (Hall, Miller & Corsellis, 1975) could contribute to diminished smooth pursuit function. Senescent changes in dopaminergic nigrostriatal pathways (McGeer, McGeer & Suzuki, 1977) could also account for some impairment of visually guided eye movements. Degeneration of nigrostriatal pathways in Parkinson’s disease is associated with impaired smooth pursuit and saccades (White, Saint-Cyr, Tomlinson & Sharpe, 1983). Degraded smooth pursuit in the elderly does not result from degeneration of the ocular motor nuclei, since they are spared in senescence (Vijayashankar & Brody, 1977). The outputs of the pursuit and saccadic systems appeared to be independent during step-ramp tracking. We found no evidence of latency interaction between smooth pursuit and saccades; a sustained smooth pursuit
209
IN AGING
acceleration usually preceded saccades when target ramps moved toward fixation, but not when they moved away from fixation. Moreover, smooth eye velocity traces showed no effect of saccades. Although its motor output is independent of pursuit, the saccadic system, like the pursuit system, receives visual motion information. The accuracy of saccades to step-ramp stimuli is best explained by the use of target velocity inputs (Gellmann & Carl, 1991). Damage to cortical motion processing areas in monkeys and humans causes inaccurate saccades to moving, but not stationary, targets, implying selective disruption of target motion inputs (Newsome et al., 1985; Thurston, Leigh, Crawford, Thompson & Kennard, 1988). The impairment of saccadic accuracy we observed in older subjects could arise from a deficit in visual motion inputs to the saccadic system. However, elderly subjects also make less accurate saccades to stationary targets (Sharpe & Zackon, 1987), demonstrating impairment of saccadic control independent of visual motion. We found that normal elderly subjects have prolonged latency of saccades to moving targets, as they do for saccades to stationary targets (Sharpe & Zackon, 1987). In our subjects, pursuit acceleration, post-saccadic pursuit velocity, peak pursuit velocity and saccadic amplitude all increased when target speed doubled, but these measures did not rise in proportion to target speed. Smooth pursuit gain fell and saccadic error rose for 40 deg/sec targets compared with 20 deg/sec targets. These findings suggest sensory limitations of target motion signals used by the smooth pursuit and saccadic systems. The population of neurons in cortical area MT in monkeys is most sensitive to retinal slip speeds between 8 and 64 deglsec, although some individual neurons have preferred speeds up to 256 deg/sec (Maunsell & Van Essen, 1983). This speed-selectivity of neurons parallels the relationship between pursuit
TABLE 2. Saccade responses in eleven normals
Saccade latency (msec)
Saccade amplitude (deg)
Position error (de&
1667 1331
206 f 76* 224 * 74
6.35 & 3.50 6.27 + 3.68
1.59 k 1.30 1.90 rt 1.43
20 deg jsec ramps Young Elderly
827 667
211 +81* 238 f 86
5.52 ;t 3.22 5.36 + 3.39
0.83 + 0.76 1.06 + 0.84
40 deg}sec ramps Young Elderly
840 664
201&71 209 & 57
7.19 + 3.61 7.18 + 3.78
2.39 + 1.28 2.74 + 1.40
N Young Elderly
Mean data rfr 1 SD, calculated from means of 20 trial types in each subject. N column signifies number of data represented in adjacent row. Upper two rows compare averages of at1 trials in six young and five elderly normal subjects; lower rows compare responses at each target speed in each age group. *P < 0.05 by Wilcoxon rank sum test, comparing young to elderly values. The age group difference in saccadic position error did not reach significance by Wilcoxon rank sum test (P = 0.09), but did so with ANCOVA (P = 0.02).
210
MARK
J. MORROW
initiation and target velocity in monkeys (Lisberger & Westbrook, 1985); pursuit eye acceleration rises very slowly or falls when target velocity exceeds 45 deg/sec. Our findings indicate that humans do not generate accurate ocular motor responses when retinal slip speeds approach 40 deg/sec. Steady-state smooth pursuit can reach higher velocities than the peak velocities we recorded to brief, unpredictable ramp targets by gradually reducing retinal slip with smooth eye acceleration. Thus, pursuit velocity in normal humans can reach 150 deg/sec for sine wave targets (Lisberger et al., 198 1); target predictability contributes to this high velocity of pursuit maintenance. REFERENCES Bagolini, B., Porciatti, V., Falsini, B., Scalia, G., Neroni, M. & Moretti, G. (1988). Macular electroretinogram as a function of age of subjects. Documenra Ophthalmologica, 70, 3743. Balazsi, A. G., Rootman, J., Drance, S. M., Schulzer, M. & Douglas, G. R. (1984). The effect of age on the nerve fiber population of the human optic nerve. American Journal of Ophthalmology, 97. 760-766. van den Berg, A. V. (1988). Human smooth pursuit during transient perturbations of predictable and unpredictable target movement. Experimental Brain Research, 72, 95-108. Brody, H. (1955). Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. Journal of Comparative Neurology, 102, 511-556. Brun, A. & Englund, E. (1981). Regional pattern of degeneration in Alzheimer’s disease: Neuronal loss and histopathological grading. Histopathology, 5, 549-564. Carl, J. R. & Gellmann, R. S. (1986). Adaptive responses in human smooth pursuit. In Keller, E. L. & Zee, D. S. (Eds), Adaptive processes in visual and oculomotor systems (pp. 335-339). Oxford: Pergamon Press. Carl, J. R. & Gellmann, R. S. (1987). Human smooth pursuit: Stimulus-dependent responses. Journal of Neurophysiology, 57, 14461463. Collewijn, H., Van der Mark, F. & Jansen, T. C. (1975). Precise recording of human eye movements. Vision Research, 15, 447450. Drance, S. M., Berry, V. & Hughes, A. (1967). The effects of age on the central isopter of the normal visual field. Canadian Journal of Ophthalmology, 2, 79982. Diirsteler, M. R. & Wurtz, R. H. (1988). Pursuit and optokinetic defects following chemical lesions of cortical areas MT and MST. Journal of Neurophysiology, 60, 9W965. Fletcher, W. A. & Sharpe, J. A. (1988). Smooth pursuit dysfunction in Alzheimer’s disease. Neurology, 38, 272--277. Gellman, R. S. & Carl, J. R. (1991). Motion processing for saccadic eye movements in humans. Experimental Brain Research, 84, 660667. Hall, T. C., Miller, A. K. H. & Corsellis, J. A. N. (1975). Variations in the human Purkinje cell population according to age and sex. Neuropathology and Applied Neurobiology, I, 267-292. Kowler, E. & Steinman, R. S. (1981). The effect ofexpectations on slow oculomotor control-III. Guessing unpredictable target displacements. Vision Research, 21, 191-203. Lisberger, S. G. & Westbrook, L. E. (1985). Properties of visual inputs that initiate horizontal smooth pursuit eye movements in monkeys. Journal of Neuroscience, 5, 166221673. Lisberger, S. G., Evinger, C., Johanson, G. W. & Fuchs, A. F. (1981). Relationship between eye acceleration and retina1 image velocity
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Acknowledgements-This research was supported by NIH Grant EY-06040, a Chisholm Memorial Scholarship, and The Toronto Hospital (Dr Morrow) and MRC of Canada Grants MT-5404 and ME-4509 (Dr Sharpe). We thank Phat Nguyen and Dr Janine Johnston for technical assistance.