Context-specific saccadic adaptation in monkeys

Jing Tian1 and David S. Zee1,2,3,4

1 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD21287, USA2 Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore,MD 21287, USA3 Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University Schoolof Medicine, Baltimore, MD 21287, USA4 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD21287, USA

AbstractWhen environmental or sensory conditions change suddenly, the brain must be capable of learningdifferent behavioral modes to produce accurate movements under multiple circumstances. A formof this dual-state adaptation known as “context-specific adaptation” has been widely investigatedusing the saccade gain adaptation paradigm in humans. In this study, we asked whether or notcontext-specific adaptation of saccade gain exists in monkeys and if so to explore its properties.Here, vertical eye position was used as a context cue for adaptation of horizontal saccade gain. Weasked for a gain increase in one context and gain decrease in another context, and then determinedif a change in the context would invoke switching between the adapted states. After training, ourmonkeys developed context-specific adaptation: in most cases gain-decrease adaptation could beinduced, but there was little or no gain-increase adaptation. This context-specific adaptationdeveloped gradually and switching of gains was evident on the first saccades with each change incontext. Along with these results, the retention of an adaptation aftereffect overnight indicates thatcontextual-specific adaptation in monkeys is not a strategy, but involves a true adaptive process ofreorganization in the brain. We suggest that context-specific adaptation in monkeys could be animportant tool to provide insights into the mechanisms of saccade adaptation that occurs duringthe more natural circumstances of daily life.

KeywordsSaccade; Adaptation; Context; Motor learning; Monkey

INTRODUCTIONMotor learning as it is usually studied in the laboratory occurs in a constrained, artificialenvironment in which the stimulus and desired response are rigidly controlled. Indeed, suchexperiments allow one to hone in on fundamental, relatively low-level mechanisms that

Corresponding author: Jing Tian, Ph.D., Department of Neurology, The Johns Hopkins Hospital, 600 N. Wolfe Street, Pathology2-210, Baltimore, MD 21287, Tel: +1-410-955-3319, Fax: +1-410-614-1746, jtian@jhmi.edu.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to ourcustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review ofthe resulting proof before it is published in its final citable form. Please note that during the production process errors may bediscovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

NIH Public AccessAuthor ManuscriptVision Res. Author manuscript; available in PMC 2011 November 23.

Published in final edited form as:Vision Res. 2010 November 23; 50(23): 2403–2410. doi:10.1016/j.visres.2010.09.014.

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underlie adaptive motor control. On the other hand, the learning that occurs during the morenatural circumstances of daily life must be optimized for a complex sensory (and motor)environment in which the particular ‘contextual’ circumstances in which the learning takesplace dictate the necessary type of response. In other words, because environmental orsensory conditions can change suddenly, the brain must be capable of learning differentbehavioral modes to produce accurate movements under multiple circumstances. Forexample, pointing movements can be adapted in a dual-state manner in the presence andabsence of a prism-induced perturbation (Mcgonigle & Flook, 1978; Welch, Bridgeman,Anand, & Browman, 1993). This form of dual-state adaptation is termed “context-specificadaptation”, and can be defined as the ability to learn and store simultaneously two differentadapted responses of a motor task, and to invoke the appropriate adapted states with theassociate context cue (e.g., Shelhamer & Clendaniel, 2002a; Shelhamer, Aboukhalil, &Clendaniel, 2005). Once learned such contextual cues can be extremely powerful; witnessthe inappropriate postural response and near fall that occurs when one takes a first step upona broken escalator (Bronstein, Bunday, & Reynolds, 2009; Reynolds & Bronstein, 2003).

Saccades are an ideal model to study motor adaptation because it is relatively easy both toartificially manipulate the stimuli that drive saccades, and to measure the consequent changein the motor response (Hopp & Fuchs, 2004; Tian, Ethier, Shadmehr, Fujita, & Zee, 2009).Adaptation of saccade gain in both humans and monkeys has been studied extensively witha conventional double-step paradigm (McLaughlin, 1967). Adaptation is usually more rapidand robust for gain decrease than increase and is slower in monkeys than in humans(Deubel, Wolf, & Hauske, 1986; Straube, Fuchs, Usher, & Robinson, 1997). Much evidenceindicates that the dorsal vermis (lobules VI–VII), the underlying posterior fastigial nucleiand perhaps the adjacent cerebellar hemispheres are crucial areas for saccadic adaptation(Alahyane et al., 2008; Barash et al., 1999; Catz, Dicke, & Thier, 2008; Choi, Kim, Cho, &Kim, 2008; Optican & Robinson, 1980; Robinson, Fuchs, & Noto, 2002; Soetedjo, Kojima,& Fuchs, 2008; Takagi, Zee, & Tamargo, 1998).

In humans, it has been well established that saccades can be made to have two differentgains in response to the same target displacement: which gain can depend on variouscontextual cues: e.g., target distance (Chaturvedi & Van Gisbergen, 1997), horizontal andvertical eye position in the orbit (Alahyane & Pelisson, 2004; Shelhamer & Clendaniel,2002a; Shelhamer et al., 2005), head orientation (Shelhamer & Clendaniel, 2002a,b), and thevisual properties of the target (Herman, Harwood, & Wallman, 2009). However, little isknown about the neural mechanisms responsible for context-dependent adaptation ofsaccade gain, and especially its anatomical substrate.

While much has been learned about saccade gain adaptation using experimental studies inmonkeys, and especially its neurophysiological underpinnings, context-specific saccadeadaptation of the type described above has not been studied in monkeys. Monkeys have beenshown to develop different gains depending upon saccade amplitude (Watanabe, Noto, &Fuchs, 2000) and the degree of disconjugate saccade adaptation that occurs to wearing aprism in front of one eye can be made to depend upon orbital position (Oohira & Zee, 1992).While such adaptive capabilities can be important, for example, in adaptation to a paresis ofa single eye muscle, it is not the ‘higher-level’ type of adaptation that we propose to studyhere. Furthermore, context-specific adaptation in monkeys could be an important tool toprovide insights into how saccade adaptation occurs in the more natural behaviors within acomplex sensory environment. Thus, we asked here whether or not context-specificadaptation of saccade gain exists in monkeys and if so to explore some of its properties. Inthis study we use the conventional saccade gain adaptation paradigm, in which horizontalsaccades of equal amplitude are alternately subjected to different adaptive demands (gain-

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increase and gain-decrease) in two different vertical eye positions (context) during the sameadaptation session.

METHODSGeneral experimental procedures

Experiments were conducted on three male rhesus monkeys (M1, M2 and M3) weighingfrom 4 to 6 kg. All experimental and surgical procedures, including anesthesia and post-operative analgesia, were performed according to a protocol that was approved by theInstitutional Animal Care and Use Committee of the Johns Hopkins University andfollowing the NIH Guidelines. The animals were first trained to come out of their cages andsit comfortably in a primate chair. For head immobilization during experiments, a plastichead plate was attached to the skull with dental acrylic. In single procedures for each eye,dual scleral coils made of stainless steel wire were implanted binocularly in M1 and in theleft eye in M2, as has been previously described (Tian, Zee, & Walker, 2007). Dual resonant“leadless” coils, small multiple-turn loop of fine wire connected to a capacitor (Roberts,Shelhamer, & Wong, 2008), were implanted in the right eye in M2 and M3. Animals weretrained to fixate and follow a small visual target for a liquid reward.

Both M1 and M2 underwent a left trochlear nerve section and M2 had an ipsilateraltrigeminal nerve (V1 and V2) section as well as part of a different study. The lesionproduced a vertical misalignment of the eyes: the paretic eye was higher than the normaleye, and this misalignment was greatest in down gaze when the paretic eye was adducted.Experiments reported here were conducted in M1 about 14 months after the superior obliquepalsy surgery and in M2 both before and 5 months after the surgery. For the adaptation datacollected after the animal had the trochlear nerve section, the normal eye was always theviewing eye (the paretic eye was patched) during the recording session and we show the datafrom the normal eye. The vertical misalignment was stable in both monkeys (6.7° ± 0.3° inM1, 5.7° ± 0.3° in M2). For M2, there was no difference in the performance of gainadaptation of horizontal saccades before and after trochlear nerve section. Accordingly weare confident that the vertical strabismus produced by the trochlear nerve section did notalter performance on the horizontal saccade adaptation paradigm. Thus all the results in agiven adaptation paradigm are pooled.

Eye movement measurementsDuring each experimental session, the animals were seated in a primate chair with headfixed. Eye movements were measured with the magnetic field search coil method in M1 andin the left eye of M2. The coil frame consisting of three orthogonal magnetic fields wasattached to the top of the primate chair, such that the head was centered within it. Signalsfrom each coil were demodulated by frequency detectors, sampled at 1000 Hz, and stored oncomputer for later analysis. For the right eye of M2 and M3, eye movements were measuredwith a “leadless” search coil system (Roberts et al., 2008), which uses a resonant coil and noconnecting lead wire. A transmitter emits a stream of pulses to the eye coil, and a receiverthen detects the resonant oscillations emitted from the eye coil. The relative intensity of thesignal as received by sets of orthogonal receiver coils determined the orientation of the eyecoil. The leadless coil system has a noise level of 0.05° peak to peak, and provides a samplerate up to 1000 Hz.

The coil signal was calibrated by requiring the animal to fix successively on targets at 5°intervals over a range of ± 20° horizontal and vertical. Calibration data were obtained withone eye viewing and the other occluded. Visual targets were back-projected using a mirror-

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controlled laser beam onto a translucent screen (72° × 72°) located 1 m in front of theanimal. The room was dimly illuminated.

Experimental paradigmsA standard double-step paradigm was used to induce an increase or a decrease in saccadeamplitude (McLaughlin, 1967). As monkeys made saccades in response to 15° horizontaltarget movements, we detected each saccade as the eye crossed a virtual 2° window placedaround the starting position. The occurrence of a saccade triggered a brief target step either5° away from (gain-increase) or 5° closer to (gain-decrease), the starting position of thesaccade. This created a visual error at the end of the movement as if the saccade had beentoo small or too large, requiring the animal to make a corrective saccade to fixate the target.This procedure, when repeated over several hundred times, gradually increased or decreasedthe saccade amplitude. We adapted saccades to both leftward and rightward targetmovements. Adapting saccades in one direction does not influence saccades in the oppositedirection (Deubel et al., 1986; Miller, Anstis, & Templeton, 1981; Straube et al., 1997), sowe treated saccades in the two directions independently.

Contextual adaptation—In this paradigm, adaptation to backward and forward targetsteps were elicited concurrently and associated with different vertical eye positions. For thegain-increase trials, an initial target was presented at left 10° (−10°). After the monkeyfixated the target for 500–1,000 ms, the target jumped to +5°. During the saccade, this targetwas displaced to +10° and maintained for 500 ms. This location then became the fixationpoint for the next trial and the same sequence was presented in the opposite direction. Forthe gain-decrease trials, the initial fixation target was presented at −5°. The first target stepwas to +10°, and the second target step was to +5°. This location then became the fixationpoint for the next trial in the opposite direction. Gain-increase adaptation was carried outwith the eyes directed up 10° above straight-ahead gaze, and gain-decrease adaptation withthe eyes directed down 10°. These two context/adaptation conditions were alternatelypresented ~30 times each, with 30 adaptation trials in each block (~1800 trials total). Theintertrial time was 750 ms. Between each change in context/adaptation condition, the animalreceived 20 s of a rest to avoid fatigue. This protocol was also repeated with the conditionsreversed. A total of 23 experiments were performed with the three monkeys.

Control adaptation—To determine the effectiveness of context-specific adaptation, acontrol adaptation paradigm was performed in M3. A single type of adaptation (gain-increase or gain-decrease) was elicited with the eyes either looking up 10° or looking down10°. This experiment was designed to look for generalization of adaptation in one context tothe second context.

Test sessions—Test trials in each context state (vertical position) were performed before(pretest, 15 trials in each direction) and after (posttest, 20 trials in each direction, testedtwice) adaptation. These were similar to the adaptation trials, except that there was nosecond target jump: the target did not reappear after the first target jump. There was thus novisual feedback as to the accuracy of the saccade, providing an open-loop measure ofsaccade gain. The fixation target for the next trial appeared 1000 ms later.

Data analysisData were analyzed offline with custom software developed in MATLAB™ (TheMathworks, Natick, MA). An interactive program was used to mark automatically the onsetand the end of saccades using velocity criteria. The onset of the saccade was defined whenthe eye velocity first exceeded 30°/sec and the end of the saccade when the eye velocity firstdropped below 30°/sec. The correctness of these markings was verified by the experimenter.

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Targeting saccades elicited by an initial target step were selected for analysis. Trials wererejected if the latency of saccade was less than 60 ms, or if the trial was contaminated byblinks. These criteria excluded approximately 5% of all saccades during contextualadaptation in M1, 7% in M3 and 11% in M2, who was a less motivated worker. The averagelatency over all the adaptation experiments was 179 ± 23 ms in M1, 236 ± 29 ms in M2 and244 ± 41 ms in M3. When we applied a latency criterion of 100 ms to assess the extent ofpredictive saccades, the number of excluded trials increased by 4% in M1 and there was nodifference in M2 and M3.

The horizontal amplitude of saccade was calculated as the difference between initial andfinal eye positions. The percent amplitude change of the saccade between the posttest andthe pretest sessions was calculated as follows: [(posttest mean amplitude − pretest meanamplitude)/pretest mean amplitude] × 100. To assess the time course of contextualadaptation, the first saccade upon each change in context was identified. This saccade givesan indication of whether or not gain switching indeed occurs immediately upon a change incontext cue, before any adaptation trials are performed. A linear regression line was fitseparately to the gain-increase and gain-decrease trials. The rate of adaptation was estimatedby the slope of regression line. We presented the results of both rightward and leftwardsaccades in normal monkeys (M2 before the surgery and M3), but only leftward saccades inM1 and M2 after the surgery, since there were more adaptation trials available for analysisin the leftward direction than the rightward.

RESULTSGeneral features

In general, we found some degree of context-specific adaptation when in one context thetarget steps backward during saccades and in the other context the target steps forward.Figure 1 shows an example of the time course of adaptation from monkey 1 (M1), who wastrained with gain-decrease adaptation with eyes down and gain-increase adaptation witheyes up. The amplitude of the leftward saccade for gain-increase and gain-decrease trials isplotted as a function of the saccade number. The saccades have an initial amplitude ofapproximately 15°, the size of the first target displacement. Little adaptation is evidentduring the first set of gain-increase trials and the subsequent set of gain-decrease trials. Asthe session progresses (the two contexts alternate), gain-decrease adaptation becomes moreclear, meanwhile gain-increase adaptation still shows a decline but at a much slower rate. Atthe end of this process, the saccades in the gain-decrease trials have become significantlysmaller; the saccades in the gain-increase trials have also become smaller but by much lessthan the gain-decrease trials. Note as was typical for all monkeys that the saccade amplitudewithin each individual context setting in the adaptation process was variable but, on average,it changed monotonically over the entire adaptation process in each context as shown by theexponential fit.

Aftereffect of adaptationThe aftereffect of adaptation was measured by comparing, before and after training, theamplitude of saccades directed towards targets that had been extinguished once the saccadebegan. Figure 2 summarizes the changes of saccade amplitude in all 23 experimentsperformed with the three monkeys. The aftereffect of training was variable acrossexperiments as seen in Figure 2 (each line represents the results from different days). Onaverage, saccade amplitude was reduced by 4.3% ± 2.3% (means ± SD) in M1, 5.9% ± 2.3%in M2 and 4.5% ± 1.5% in M3 after gain-decrease adaptation, which is consistent with theexpected effect in the appropriate context (gaze directed down as well as up). However, theadaptation was less effective in the gain-increase context (gaze directed up as well as down

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except for gaze down in M3), as the saccade amplitude slightly decreased by 0.8% ± 1.8% inM1, increased by 1.8% ± 3.5% in M2 and 3.0% ± 4.0% in M3. Nevertheless, in all animals,the changes generated in the gain-increase and gain-decrease conditions were significantlydifferent (Wilcoxon signed rank test; p < 0.01), which suggests that context specificity canoccur in saccadic gain adaptation in monkeys when the training involves conflicting saccadeamplitude changes.

To find out whether the context-specific adaptation was as effective as a single adaptationand to assess the generalization of adaptation in one context to the second context, we alsotested gain decrease or gain increase at up or down positions as controls in M3. Figure 3summarizes the changes of saccade amplitude in all 8 control experiments. On average,saccade amplitude was reduced by 9.7% ± 3.0% at up position and 11.7% ± 3.8% at downafter gain-decrease adaptation; average gain transfer to the second position was 48% and74%, respectively. The amplitude increased by 4.0% ± 0.7% at up position and 10.3% ±5.1% at down after gain-increase adaptation; average gain transfer to the second positionwas 162% and 46%, respectively. Both the gain-increase and gain-decrease adaptations weremore effective in control conditions than in context-specific conditions, which indicates thatgain-increase and gain-decrease adaptation interacted when they were performedsimultaneously in a single session. Secondly, the gain-increase adaptation was more robustwhen gaze was directed down than up, which was consistent with what we found duringcontextual adaptation (Fig. 2, right side of M3 panel).

Time course of adaptationTo quantify the time course of adaptation, we plotted the amplitude of the first saccade uponeach change in context state as a function of the set number (Figure 4, from the same data asshown in Fig 1). This indicates whether or not the amplitudes of the saccades changeimmediately upon a change in context state. Regression lines were fit separately to the gain-increase trials and to the gain-decrease trials. Figure 4 shows the evidence of switchingbetween the increased-gain state and the decreased-gain state immediately upon each changein context. As adaptation progresses, this context specificity increases in size as seen by thedivergence of the regression lines.

Figure 5 summarize the slopes of the regression lines (as illustrated in Fig. 4) in all 23contextual adaptations. Similar to the aftereffect of adaptation (Fig 2), the rate of adaptationvaried from animal to animal and from day to day for a particular animal. On average, thegain-decrease adaptation was more rapid than the gain-increase adaptation except for gazeup in M3. The differences between the slopes of the gain-increase trials and the gain-decrease trials were significant in M2 and M3 (Wilcoxon signed rank test; p < 0.01), butmissed being significant in M1 (p = 0.078).

The data above demonstrated that the adapted state switched immediately upon the changein context state, suggesting a mechanism for contextual switching that did not require thereappearance of an error signal to invoke the context-specific response, i.e., a feedforwardcontrol mechanism. To assess this further, we examined the difference in amplitudesbetween the first two saccades upon each change in context state. If retinal error from thefirst saccade is used to determine that a change in context state has occurred, then the secondsaccade after experiencing an error should show increased context-specificity (largerregression slopes) relative to the first. The slopes of regression lines fit to the first saccadeand the second saccade for both gain-increase and gain-decrease trials are shown in Figure6. It is clear that there is no significant difference in the time course of adaptation asassessed with first saccades or second saccades upon each context switch for both rightwardand leftward saccades (Wilcoxon signed rank test; p > 0.1). Again, this result supports afeedforward mechanism for control of context switching.

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Long-term context-specific adaptationIn an attempt to test whether or not the long-term training over days can improve thecontextual learning, monkey 2 was subject to the same context-specific adaptation session(only rightward saccades were adapted) for three days. The animal underwent normal visualexperience after each day’s test. Figure 7 shows the amplitude of the adapted saccadesduring the three day contextual adaptation. On all three days, M2 exhibited a typical patternof context-specific learning as shown in Fig 1: gain-decrease adaptation is evident, but gain-increase adaptation remains marginal.

To compare saccade amplitude between different days, we plot in Figure 8 saccadeamplitude as a function of the test sessions (from before to after adaptation). For thesaccades in the gain-increase context, the amplitude changed little over three days (Kruskal-Wallis test; p = 0.12). For the saccades in the gain-decrease context, the mean amplitude oftest trials decreased significantly from 14.9° ± 0.7° to 13.0° ± 0.6° on day 1 (Wilcoxon ranksum test; p< 0.01). At the start of day 2, saccade amplitude recovered to 13.9° ± 0.4°, butwas still significantly smaller than day 1 pretest amplitude (p< 0.01). By the end of day 2,saccade amplitude decreased to 13.2° ± 0.5°. At the start of day 3, saccade amplitudechanged very little overnight (p = 0.13). By the end of day 3, it decreased to 11.9° ± 0.5° andthe difference between the two adapted states was larger than that on day 1. Most striking isthe retention of the context-specific adaptation at the beginning of day 2 and day 3 asindicated by the arrows in Fig 7. This indicates the two different gain states produced by thecontextual paradigm reflect a true neuronal plasticity. From this we conclude that eyeposition information is used as a contextual signal both during the adaptation and retentionperiods, allowing the saccadic system to switch state between high or low gains.

DISCUSSIONHere we show in monkeys that saccades in response to the same-sized target displacementcan be simultaneously adapted to exhibit different gains which depend on vertical eyeposition (context). As has been shown in humans, this context-specific adaptation developsgradually and switching of gains is evident on the first saccades with each change in context.Furthermore, our results demonstrate that contextual adaptation involving conflicting errorsignals was less robust than the non-contextual adaptation, probably due to the interferencebetween context/adaptation states.

Context-specific adaptation can occur in monkeysA previous study has reported that saccades can be made to have two different gainsdepending on their amplitude in monkeys (Watanabe et al., 2000). Here we asked ifmonkeys can perform a more complicated task, in which we ask them to invoke a morecomplicated, presumably higher-level adaptive response that is tailored to a specific context.“Context” here refers to a condition that is not usually thought of as influencing theperformance of a motor task (Shelhamer & Clendaniel, 2002a; Shelhamer et al., 2005).Thus, the adaptation may be low-level, whereas the contextual switching is higher-level. Weused vertical eye position as a context for adaptation of horizontal saccades in response tothe same target displacement. We asked if the monkeys could learn a gain increase in onecontext and a gain decrease in another context, and then determined if a change in thecontext would invoke immediate switching between the two different gain states. In theabsence of context-specificity, one might expect the gain-increase and gain-decreaseadaptation to cancel each other and produce no adaptive changes at worst or only one of thetwo adaptations at best. Our results indicate this is not the case: in most experiments gain-decrease adaptation could be induced, but there was little or no gain-increase adaptation.Nevertheless, there was a significant difference between the two simultaneous modifications

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of saccade amplitude according to vertical eye position. As pointed out in prior studies inhuman beings (Shelhamer & Clendaniel, 2002a,b; Shelhamer et al., 2005), this isnevertheless a demonstration of context-specific adaptation, since each change in contextinvokes clear switching of gain states, even if one of the states does not exhibit significantadaptation. One might ask why the brain needs a mechanism to make horizontal eyemovements dependent on vertical eye position. Takagi et al. (2000) suggested a mechanismbased on context-specific adaptation of pursuit and similar considerations apply to saccades.Obliquely directed movements, which occur often naturally, demand different horizontalinnervations depending on the vertical position of the eye because of the change in pullingdirections of the horizontal muscles with vertical eye position. Accordingly vertical eyeposition could be an effective contextual cue for the appropriate horizontal innervationsneeded to make an accurate saccade.

One can ask if the vertical strabismus produced by the trochlear nerve section (part of adifferent study) affected the contextual adaptation in our monkeys, since two of the threecontextual adaptation experiments performed before M2 had the nerve section appeared tohave a greater aftereffect than those after, and the adaptation in M1 was even weaker.Taking the results together in all three monkeys, however, we think it unlikely that thestrabismus had a major effect on the contextual adaptation in the two operated monkeys. Thevariability of adaptation itself, from animal to animal and from day to day for a specificanimal makes it difficult to make a firm conclusion about the strabismus. Furthermore, theamount of aftereffect after conventional adaptation was similar before and after the nervesection in M2 (data not shown). Accordingly we are confident that the vertical strabismusdid not alter the performance of the horizontal saccade adaptation per se and, especiallyconsidering that the monkey was always tested with only the intact eye viewing.

Comparison to studies with humansIn humans, two previous studies have investigated the context specificity of saccadeadaptation using vertical eye position as a context (Alahyane & Pelisson, 2004; Shelhamer& Clendaniel, 2002a). Our findings in monkeys are most similar to those of Shelhamer andClendaniel (2002a), who found there was considerable undesired transfer from gain-decrease adaptation to gain-increase adaptation, with the result that there was little gain-increase adaptation. However, Alahyane and Pelisson (2004) reported that significantadaptation can be induced not only in the gain-decrease context but also in the gain-increasecontext. One possible reason for this difference, as has been suggested (Alahyane &Pelisson, 2004), is that the two vertical eye positions where the conflicting adaptations weretested were farther away from each other in their study (up 12.5° and down 25°) than in oursand Shelhamer and Clendaniel’s experiments (up 10° and down 10°). The closer the twocontexts are, the less effective it might be to prevent transfer of adaptation from gain-decrease condition to the gain-increase condition. A similar spatial extent effect is seen, forexample, in disconjugate saccade adaptation in monkeys in response to wearing a laterally-displacing hemifield prism in front of one eye (Oohira & Zee, 1992).

The efficacy of different context cues (sensory and motor) has been assessed in prior studies(Shelhamer & Clendaniel, 2002a,b). Eye position in the orbit is an example of a motorcontext cue: the motor commands sent to the muscles to generate a particular movement aredifferent in the two context states. Head roll-tilt is an example of a sensory cue as head tilt issensed by the otoliths and proprioception but saccades are always same in the head. It hasbeen demonstrated that the motor context (change in saccade direction) is relatively strongerthan the sensory context (head roll-tilt) (Shelhamer & Clendaniel, 2002b), and horizontaleye position was more effective than vertical eye position for demonstrating context-specificadaptation of horizontal saccades (Shelhamer & Clendaniel, 2002a). Taken together, theseresults suggest that a context cue is more effective when it is immediately relevant to the

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movement being adapted since naturally occurring adaptation is more commonly a motorrepair than a sensory remapping mechanism. However, this notion has been challenged by arecent study of Herman et al. (2009), who reported that a visual context (stable/flickingtarget) can serve as an effective contextual cue for saccade adaptation, although an earlierattempt with target color had been unsuccessful (Deubel, 1995). It may be that the ability tomodify saccade gains based on the target visual properties reflects a much higher level andmore sophisticated cognitive type of adaptation.

Another difference among these studies is the trial structure of contextual paradigm: twodifferent adaptations in two contexts has been alternated randomly across successive trials(Alahyane & Pelisson, 2004; Deubel, 1995), in blocks of fixed length (Shelhamer &Clendaniel, 2002a,b), or short blocks of irregular length (Herman et al., 2009). Althoughrandom context presentation may slow contextual learning since half of the adaptation trialswould be preceded by trials with different or opposite error signals, one study has shownrobust adaptation in humans (Alahyane & Pelisson, 2004). In monkeys, we chose toalternate the gain-increase and gain-decrease adaptations in blocks (30 trials), becauseadaptation in monkeys is much slower than in humans and also in this way undesiredsaccades when switching the contexts (between two vertical eye positions) can be avoided.With this protocol, our monkeys exhibit context-dependent learning though it is notcomplete. Further study will be required to determine how the trial structure affects theextent and time course of context-specific adaptation.

Context-specific adaptation process is a true neuronal plasticityOne might question whether our monkeys used a cognitive strategy to alter their saccades indifferent contexts since the target locations were predictable. Several lines of evidence argueagainst the idea that their contextual adaptation was strategic. First, the adaptation developedgradually over thousands of trials and generally gain-decrease adaptation was moredeveloped than gain-increase adaptation. This is also the case with conventional saccadeadaptation and supports the idea that our data reflect true adaptation, not a cognitivestrategy. Second, as adaptation proceeds, switching of adapted gains upon each change incontext occurred immediately. Thus, an initial saccade was not necessary to provide retinalerror feedback in order to trigger saccades of appropriate gain. Third, contextual adaptationwas weakened by the interference between the gain-increase and gain-decrease adaptations,suggesting that volitional control of this process is unlikely. Finally, there was some residualamplitude change the day after an experiment, despite the fact that monkey had normalvisual experience in between. If contextual adaptation were strategic, we would not expectthe strong retention after the animal had spent 24 h in their natural visual environment.Similar retention of gain change induced by conventional saccade adaptation has also beenfound in humans (Alahyane & Pelisson, 2005) and in monkeys (Noto, Watanabe, & Fuchs,1999). It may appear surprising that the adaptation can be retained over days, despite thesubjects having received visual feedback from many saccades made during their dailyactivities. One possible explanation is that the amplitude of saccades generated naturally isdifferent from that of adapted saccades during the experiments. It has been reported thatmost naturally occurring saccades in humans are less than 15° (Bahill, Adler, & Stark,1975). Another possible factor would be that internally triggered saccades have little effecton de-adaptation of visually triggered saccades performed in the laboratory. Taken together,these results suggest that contextual-specific adaptation cannot be controlled voluntarily, butinvolves a true adaptive process of reorganization in the brain.

Neuronal substrate of context-specific adaptationThe neuronal substrates of conventional (non-contextual) saccadic adaptation have beenextensively investigated. A variety of neurophysiological studies demonstrated that the

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cerebellum is critically involved in saccadic adaptation (Barash et al., 1999; Catz et al.,2008; Optican & Robinson, 1980; Robinson et al., 2002; Soetedjo et al., 2008; Takagi et al.,1998). However, much less is known about the neuronal site of context-specific adaptation.In a monkey reaching study with prism adaptation, it has been shown that pointing responsescan be differentially adapted for each viewing eye. This capability was lost after focallesions of the dorsal vermal and paravermal cerebellar cortex, but in the same animals non-contextual adaptation to a prism was spared, suggesting that these regions of cerebellum arerequired in context-dependent motor learning (Lewis & Tamargo, 2001). Based on theseresults, the cerebellum is a possible candidate area for context-specific saccadic adaptation.

Recently, Lee and Schweighofer (2009) proposed that a parallel model with a fast and aslow process can explain the dual or multiple motor adaptations. In their model, the fastprocess contains only a single state and the slow process contains multiple states switchedvia context cues. In the case of conventional saccadic adaptation, a similar two-timescaleprocess has been observed in a gain adaptation paradigm (Ethier, Zee, & Shadmehr, 2008),and in a cross-axis adaptation paradigm (Chen-Harris, Joiner, Ethier, Zee, & Shadmehr,2008). In human patients with cerebellar degeneration including the vermis andhemispheres, a recent study demonstrated that the fast process of adaptation was absent, butthe slow process was less impaired (Xu-Wilson, Chen-Harris, Zee, & Shadmehr, 2009). Thissuggest that the damage to the cerebellar cortex mostly affects the fast process of adaptation,and supports the idea that the two processes derive from different neural mechanisms andpossibly have different anatomical substrates. Similarly, in a monkey lesion study, Barash etal. (1999) proposed that a fast and a slow process that adjust the saccade gain depend on thecerebellar cortex and nuclei separately. Context-specific adaptation involves recruitment ofdifferent adaptation modules for different contexts and increases the complexity of itsunderlying neural circuitry. The precise role played by separate cerebellar loci, or other partsof the brain, in contextual adaptation, especially in learning, storage and retrieval ofdifferent adapted states, need to be elucidated. To this important and topical question abouthow the brain learns new behaviors, the monkey model of contextually driven saccadeadaptation can provide critical information.

• Context-specific adaptation of saccade gain exists in monkeys.

• Switching of gains is evident on the first saccades with each change in context.

• Retention of aftereffect indicates a true adaptive process of brain reorganization.

AcknowledgmentsThis study was supported by the National Institutes of Health (R01-EY01849); the Albert Pennick fund; Leon LevyFoundation; and by the Arnold-Chiari Foundation. Dr. Tian is a Paul and Betty Cinquegrana Scholar. C. Bridges,A. Lasker, and D. Roberts provided technical support. The authors are grateful to M. Shelhamer for a criticalreview and discussion of this manuscript.

Reference ListAlahyane N, Fonteille V, Urquizar C, Salemme R, Nighoghossian N, Pelisson D, et al. Separate neural

substrates in the human cerebellum for sensory-motor adaptation of reactive and of scanningvoluntary saccades. Cerebellum. 2008; 7:595–601. [PubMed: 19009327]

Alahyane N, Pelisson D. Eye position specificity of saccadic adaptation. Investigative Ophthalmology& Visual Science. 2004; 45:123–130. [PubMed: 14691163]

Alahyane N, Pelisson D. Long-lasting modifications of saccadic eye movements following adaptationinduced in the double-step target paradigm. Learning Memory. 2005; 12:433–443. [PubMed:16077021]

Bahill AT, Adler D, Stark L. Most Naturally Occurring Human Saccades Have Magnitudes of 15Degrees or Less. Investigative Ophthalmology. 1975; 14:468–469. [PubMed: 1132942]

Tian and Zee Page 10

Vision Res. Author manuscript; available in PMC 2011 November 23.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

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-PA Author Manuscript

Barash S, Melikyan A, Sivakov A, Zhang M, Glickstein M, Thier P. Saccadic dysmetria andadaptation after lesions of the cerebellar cortex. Journal of Neuroscience. 1999; 19:10931–10939.[PubMed: 10594074]

Bronstein AM, Bunday KL, Reynolds R. What the “Broken Escalator” Phenomenon Teaches Us aboutBalance. Basic and Clinical Aspects of Vertigo and Dizziness. 2009; 1164:82–88.

Catz N, Dicke PW, Thier P. Cerebellar-dependent motor learning is based on pruning a Purkinje cellpopulation response. Proceedings of the National Academy of Sciences USA. 2008; 105:7309–7314.

Chaturvedi V, vanGisbergen JAM. Specificity of saccadic adaptation in three-dimensional space.Vision Research. 1997; 37:1367–1382. [PubMed: 9205728]

Chen-Harris H, Joiner WM, Ethier V, Zee DS, Shadmehr R. Adaptive control of saccades via internalfeedback. Journal of Neuroscience. 2008; 28:2804–2813. [PubMed: 18337410]

Choi KD, Kim HJ, Cho BM, Kim JS. Saccadic adaptation in lateral medullary and cerebellarinfarction. Experimental Brain Research. 2008; 188:475–482.

Deubel, H. Is saccade adaptation context-specific?. In: Findlay, JM.; Walker, R.; Kentridge, RW.,editors. Eye movement research: mechanisms, processes and applications. Amsterdam: ElsevierScience; 1995. p. 177-187.

Deubel H, Wolf W, Hauske G. Adaptive gain control of saccadic eye movements. HumanNeurobiology. 1986; 5:245–253. [PubMed: 3818374]

Ethier V, Zee DS, Shadmehr R. Spontaneous recovery of motor memory during saccade adaptation.Journal of Neurophysiology. 2008; 99:2577–2583. [PubMed: 18353917]

Herman JP, Harwood MR, Wallman J. Saccade Adaptation Specific to Visual Context. Journal ofNeurophysiology. 2009; 101:1713–1721. [PubMed: 19164105]

Hopp J, Fuchs AE. The characteristics and neuronal substrate of saccadic eye movement plasticity.Progress in Neurobiology. 2004; 72:27–53. [PubMed: 15019175]

Lee JY, Schweighofer N. Dual Adaptation Supports a Parallel Architecture of Motor Memory. Journalof Neuroscience. 2009; 29:10396–10404. [PubMed: 19692614]

Lewis RF, Tamargo RJ. Cerebellar lesions impair context-dependent adaptation of reachingmovements in primates. Experimental Brain Research. 2001; 138:263–267.

Mcgonigle BO, Flook J. Long-Term Retention of Single and Multistate Prismatic Adaptation byHumans. Nature. 1978; 272:364–366. [PubMed: 634364]

McLaughlin S. Parametric adjustment in saccadic eye movements. Perception & Psychophysics. 1967;2:359–362.

Miller JM, Anstis T, Templeton WB. Saccadic plasticity: parametric adaptive control by retinalfeedback. Journal of Experimental Psychology: Human Perception and Performance. 1981; 7:356–366. [PubMed: 6453929]

Noto CT, Watanabe S, Fuchs AF. Characteristics of simian adaptation fields produced by behavioralchanges in saccade size and direction. Journal of Neurophysiology. 1999; 81:2798–2813.[PubMed: 10368398]

Oohira A, Zee DS. Disconjugate ocular motor adaptation in rhesus monkey. Vision Research. 1992;32:489–497. [PubMed: 1604836]

Optican LM, Robinson DA. Cerebellar-dependent adaptive control of primate saccadic system. Journalof Neurophysiology. 1980; 44:1058–1076. [PubMed: 7452323]

Reynolds RF, Bronstein AM. The broken escalator phenomenon - Aftereffect of walking onto amoving platform. Experimental Brain Research. 2003; 151:301–308.

Roberts DC, Shelhamer M, Wong A. A new “wireless” search-coil system. Proceedings of the 2008symposium on Eye tracking research & applications. 2008:197–204.

Robinson FR, Fuchs AF, Noto CT. Cerebellar influences on saccade plasticity. Annals of the NewYork Academy of Sciences. 2002; 956:155–163. [PubMed: 11960801]

Shelhamer M, Aboukhalil A, Clendaniel R. Context-specific adaptation of saccade gain is enhancedwith rest intervals between changes in context state. Annals of the New York Academy ofSciences. 2005; 1039:166–175. [PubMed: 15826971]

Tian and Zee Page 11

Vision Res. Author manuscript; available in PMC 2011 November 23.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Shelhamer M, Clendaniel RA. Context-specific adaptation of saccade gain. Experimental BrainResearch. 2002a; 146:441–450.

Shelhamer M, Clendaniel R. Sensory, motor, and combined contexts for context-specific adaptation ofsaccade gain in humans. Neuroscience Letters. 2002b; 332:200–204. [PubMed: 12399014]

Soetedjo R, Kojima Y, Fuchs AF. Complex spike activity in the oculomotor vermis of the cerebellum:a vectorial error signal for saccade motor learning? Journal of Neurophysiology. 2008; 100:1949–1966. [PubMed: 18650308]

Straube A, Fuchs AF, Usher S, Robinson FR. Characteristics of saccadic gain adaptation in rhesusmacaques. Journal of Neurophysiology. 1997; 77:874–895. [PubMed: 9065856]

Takagi M, Abe H, Hasegawa T, Usui T, Hasebe H, Miki A, et al. Context-specific adaptation ofpursuit initiation in humans. Investigative Ophthalmology & Visual Science. 2000; 41:3763–3769.[PubMed: 11053274]

Takagi M, Zee DS, Tamargo R. Effects of lesions of the oculomotor vermis on eye movements inprimate: saccades. Journal of Neurophysiology. 1998; 80:1911–1930. [PubMed: 9772249]

Tian J, Ethier V, Shadmehr R, Fujita M, Zee DS. Some perspectives on saccade adaptation. Annals ofthe New York Academy of Sciences. 2009; 1164:166–172. [PubMed: 19645895]

Tian J, Zee DS, Walker MF. Rotational and translational optokinetic nystagmus have differentkinematics. Vision Research. 2007; 47:1003–1010. [PubMed: 17320142]

Watanabe S, Noto CT, Fuchs AF. Flexibility of saccade adaptation in the monkey: different gain statesfor saccades in the same direction. Experimental Brain Research. 2000; 130:169–176.

Welch RB, Bridgeman B, Anand S, Browman KE. Alternating Prism Exposure Causes DualAdaptation and Generalization to A Novel Displacement. Perception & Psychophysics. 1993;54:195–204. [PubMed: 8361835]

Xu-Wilson M, Chen-Harris H, Zee DS, Shadmehr R. Cerebellar Contributions to Adaptive Control ofSaccades in Humans. Journal of Neuroscience. 2009; 29:12930–12939. [PubMed: 19828807]

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Figure 1.An example of the time course of context-specific adaptation from M1. The amplitude of theleftward saccade for gain-increase and gain-decrease trials is plotted as a function of saccadenumbers. × indicates the saccade amplitudes for gain-increase trials with eye up 10°, and ○for gain-decrease trials with eyes down 10°. Solid curves are exponential fits. Test trialsbefore and after adaptation are set off by dotted vertical lines.

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Figure 2.Changes of saccade amplitude between the posttest and the pretest trials in all 23 context-specific adaptation experiments. Each black line represents the results of leftward saccadesfor each individual day and grey line represents the results of rightward saccades. Thesuperimposed bars indicate the mean values. ◇ indicates the results if the monkeys wereintact. * beside the data points indicates the change was significantly different in the panelof M1 and M2. For M3, * and ns below the data points indicate the change was significantand nonsignificant for all the points above; otherwise all the changes were significant exceptindicated as ns.

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Figure 3.Changes of saccade amplitude between the posttest and the pretest trials in all 8 controladaptation experiments in M3. Each black line represents the results of leftward saccades foreach individual day and grey line represents the results of rightward saccades. Thesuperimposed bars indicate the mean values. All the changes were significant exceptindicated as ns.

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Figure 4.The first adaptation trial upon each change in context state during the course of adaptation inM1. Consecutive set numbers are along the abscissa. Lines were fit separately to the gain-increase and gain-decrease trials using a least squares algorithm, to quantify the time courseof adaptation.

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Figure 5.Summary of the slopes of the regression lines illustrated in Figure 4 for all 23 context-specific adaptation experiments. Each black line represents the results of leftward saccadesfor each individual day and grey line represents the results of rightward saccades. Thesuperimposed bars indicate the mean values. ◇ indicates the results if the monkeys wereintact. * beside the data points indicates the slope was significantly different from zero.

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Figure 6.The slopes of regression lines fit to the first saccade and the second saccade upon eachcontext switch for both gain-increase and gain-decrease trials in all 23 context-specificadaptation experiments. Black line represents the results of leftward saccades and grey linerepresents the results of rightward saccades. It is clear that the second saccade does notsystematically exhibit greater adaptation than the first for both rightward and leftwardsaccades.

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Figure 7.Saccade amplitude changes during the three-day context-specific adaptation in M2. ×indicates the saccade amplitudes for gain-increase trials with eye up 10°, and ○ for gain-decrease trials with eyes down 10°. Test trials before and after adaptation are set off bydotted vertical lines for each day. Arrows indicate the retention of adaptation at thebeginning of day 2 and day 3.

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Figure 8.Mean saccade amplitude plotted as a function of the test sessions of the three- day context-specific adaptation in M2. × indicates the saccade amplitudes of test trials in the gain-increase context (with eye up 10°), and ○ in the gain-decrease context (with eyes down 10°).Error bars are SD.

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