Jillian H. Fecteau and Douglas P. Munoz

Transcription

1 EXPLORING THE CONSEQUENCES OF THE PREVIOUS TRIAL Jillin H. Fecteu nd Dougls P. Munoz In tsks tht re designed to explore cognitive functioning, the response on ech tril is function of the comintion of experimentl conditions tht occurred on tht nd the previous tril. Becuse the previous tril influences performnce, the event presented during or the ction required y the previous tril must leve n imprint on the rin s ctivity tht crries through to the next tril. These imprints re mnifest in the ctivity of single neurons tht prticipte in producing the response. Previous tril effects ddress disprte cognitive phenomen, such s response priming, tsk switching nd inhiition of return, nd the neurl ses of previous tril effects cn e envisioned s chnges in slience of the trget or the gol of the ction on sptil mp. TASK SET The sme stimulus (for exmple, ringing phone) cn produce different responses (lift versus do not lift receiver) depending on the sitution (your office versus someone else's). Tsk set refers to the wy of responding tht is dopted in given sitution. Tsk-switching experiments mesure the costs involved when switching etween sets. Centre for Neuroscience Studies, Deprtment of Physiology, Queen s University, 4th Floor, Botterell Hll, Kingston, Ontrio K7L 3N6, Cnd. e-mil: doug@eyeml.queensu.c doi: /nrn1114 Imgine flipping through photogrph lum. A lot of informtion is contined in ech picture. For instnce, it is possile to guess the pproximte ge of the photogrph on the sis of the clothing nd hirstyles worn y the people posing for the shot, nd the purpose of the gthering when pproprite props re included in the picture. All of this informtion cn e gthered from single picture ecuse pictures ccurtely cpture one instnt in time. Knowing wht hppened t one instnt cnnot disclose how tht moment cme into eing, though. For instnce, picture depicting mn, sleeping in chir, while wering tuxedo, mkeup nd tir indictes tht he ws the trget of prnk fter he hd too much to drink. However, from this picture we cnnot know who the prnkster ws or whether lcohol ws involved. Mny studies of humn perception nd cognition re conceptully similr to looking t single photogrphs. Consider typicl rection-time study. The mount of time tht is required to respond to stimulus is compred etween t lest two conditions. When systemtic differences in rection time re otined, the condition tht evokes shorter rection times is thought to require fewer steps or computtions, or to involve more efficient processes, thn the condition tht evokes longer rection times 1 5. To provide n ccurte representtion of the conditions under study, ech condition is tested severl times, which ssures stle estimte of rection time, nd different conditions re presented in rndom order, which excludes systemtic ordering effects. Even though ech condition is smpled severl times, this tctic is still equivlent to tking single picture ecuse ll of the informtion tht ws otined for ech condition is lended into one instnce, mking it impossile to ssess whether preceding events influenced the outcome of ech tril. Does the previous tril influence responding on the next tril? To nswer this question, reserchers compre the outcome of ech tril on the sis of the tril tht preceded it. Doing so shows tht the conditions on the previous tril cn increse or decrese response time, nd cn lter the trjectory of the response, depending on the tsk nd circumstnces. When reported, these previous tril effects hve een interpreted s the consequences of priming 6 15, procedurl lerning 8,16, mintining or switching TASK SET 17 20, ttention 21 25, guessing strtegies 26,27 or competing motor progrms 28. Despite these differences in tsks nd interprettions, common theme remins preceding events modify performnce. Oserving previous tril effects in ehviour indictes tht informtion presented during, or the ctions required y, the previous tril leve residul imprint on the rin tht crries through to the next tril. To find out how these imprints re mnifest, the ctivity of single neurons is monitored while monkeys perform cognitive tsks tht generte previous tril effects. NATURE REVIEWS NEUROSCIENCE VOLUME 4 JUNE

2 Box 1 Sccdic eye movements nd oculomotor neurophysiology DLPFC Fixtion Trget Sccde Fixtion Trget Sccde FEF To eye muscles SEF CN SNp MRF PPRF Visul cortex Sccdic eye movements re the response of choice in experiments involving non-humn primtes ecuse they re simple, stereotyped ctions for which the neurontomicl sustrtes hve een estlished ( simplified version is shown in prt ) nd ecuse the neurophysiologicl chrcteristics of the neurons in severl of these structures hve een descried In the studies discussed in this review, neurons in the superior colliculus (SC) nd frontl eye fields (FEF) were monitored while monkeys generted sccdes to visul trgets. Prt shows spike-density wveforms from visuomotor neurons in the superior colliculus (red) nd frontl eye fields (lue) for memory-guided sccde tsk (upper pnel; trget is presented nd extinguished, nd the monkey initites sccde to the rememered loction of the trget) nd gp sccde tsk (lower pnel; the fixtion light disppers for 200 ms efore the trget ppers). Both neurons show two peks of ctivity. The first is sensory signl tht egins ms fter the trget ppers nd tht occurs even when sccde is not generted 95,99. The second is motor signl tht precedes the initition of the sccde y ms 95,100 nd tht ppers only when sccde is out to e generted 101,102. The strength of the motor urst in the superior colliculus is relted to sccdic velocity 103,104. Two other cognitive signls cn e seen in these tsks (or fter smll modifictions to the tsks). Motor preprtion is represented s low-frequency tonic ctivity during the tril, which increses when monkeys prepre to mke sccde into the neuron s response field 32 when they expect the trget to pper t tht position 30,33, when they covertly ttend to tht loction 105, or when they choose to initite sccde to tht loction 106. This incresed low-frequency ctivity hs een interpreted s motor preprtion ecuse the monkeys pln to initite sccde to the trget s loction in every exmple. Trget selection is the second cognitive signl tht is oserved in the frontl eye fields nd superior colliculus 41, nd is discussed further in the section on visul serch. CN, cudte nucleus; DLPFC, dorsolterl prefrontl cortex; LIP, lterl intrprietl cortex; MRF, medullry reticulr formtion; PPRF, prmedin pontine reticulr formtion; SEF, supplementry eye fields; SNp, sustnti nigr prs reticult. SC Memory-guided sccde tsk Sensory Sensory Motor preprtion Gp sccde tsk Motor preprtion LIP Cereellum Motor Motor 200 ms 100 spikes s 1 Arrnging neurophysiologicl dt in chronologicl order nd correlting these chnges in the neurons ctivity with the chnges in ehviour shows how the previous tril exerted its influence. Here, we descrie the neurophysiologicl ses of previous tril effects. Ech of the studies discussed hs reported different ehviourl consequences of the previous tril. All of these studies hve used oculomotor tsks nd hve monitored the ctivity of oculomotor neurons in the frontl eye fields nd superior colliculus. For reders not fmilir with the oculomotor system, BOX 1 descries why sccdic eye movements re the response of choice in mny non-humn primte experiments, nd it summrizes the sic neurl signtures tht correspond to sensory, motor nd cognitive processes. In BOX 2,we introduce the concept of slience mp, which provides simple nd effective wy to envision the influence of the previous tril on sptil mps tht re similr to those of the frontl eye fields nd superior colliculus. We egin y descriing the simplest exmple of previous tril effects tht hve een documented those oserved during two-lterntive choice rection-time tsk. Two-lterntive choice tsks In the two-lterntive choice SACCADE tsk, monkeys generte sccde to visul trget tht ppers to the left or right of the centre. The solute loction of the trget (left versus right) hs little influence on performnce. However, the reltive loction of the trget does hve n influence: sccdic rection times re fster when consecutive trgets pper t the sme loction thn when they pper t different loctions 29 (FIG. 1). How is this repetition dvntge expressed in the ctivity of single neurons? FIGURE 1 shows tht the ctivity of neuron ws elevted (rrow) efore the trget ws registered y the neuron when the previous tril ws generted to the sme loction (in lue) compred with when it ws generted to the opposite loction 30,31 (in red). This increse in pre-trget ctivity, which ws oserved cross the popultion of neurons in this study (FIG. 1c, right), shortens sccdic rection time y llowing the threshold of ctivity for generting sccde to e reched sooner (FIG. 1c, left). In support of this notion, the mgnitude of pre-trget ctivity predicts sccdic rection times on tril-y-tril sis: incresed pre-trget ctivity is ssocited with shorter sccdic rection times 30 (FIG. 1d; individul neuron, left; popultion, right). In other words, the repetition dvntge in sccdic rection times occurs when elevted pre-trget ctivity increses the slience of loclized region on the sccdic mp, which rings this region closer to threshold for inititing sccde (BOX 2). Although this study shows cler-cut reltionship etween ehviour nd neurl ctivity, two issues remin unexplined. First, we do not know wht is responsile for the elevted pre-trget ctivity. In previous studies, incresed pre-trget ctivity hs een ssocited with motor preprtion 32,33. However, there is no reson for monkeys to nticipte repeted ction when the trget is eqully likely to pper t either side. Indeed, mnipulting the likelihood 2 JUNE 2003 VOLUME 4

3 Box 2 Slience mps in the frontl eye fields nd superior colliculus Activity SACCADE A rpid eye movement (with speeds of up to 800 s 1 ) tht rings the point of mximl visul cuity the fove to the imge of interest. Threshold for inititing ction Vrile rte of rise The slience mp, which is often used in computtionl models of ttentionl shifting 77 79, is useful concept for this rticle ecuse it provides simple wy to envision chnges in neurl ctivity tht re ssocited with the previous tril. A slience mp is two-dimensionl, topogrphiclly orgnized mp tht represents the distinctiveness of ojects in the visul scene. This mp cn e modified, or tuned, y the gols of the oserver 78. This concept is illustrted in prt. Two slient ojects re presented in the visul scene (left): red verticl r nd lue verticl r mong lue horizontl rs. In response to this scene, two peks of ctivity (represented y umps) occur on the slience mp (right). The red r results in greter level of ctivity ecuse it differs from other ojects in the scene in two wys (colour nd orienttion), wheres the lue verticl r differs from the other ojects only in orienttion. The region with the highest level of ctivity is chosen s the next trget of ttention. The frontl eye fields 107 nd the superior colliculus 40 shre severl key fetures with this theoreticl slience mp The neurl ctivity tht is linked to visul ojects represents the slience of these ojects in the overll level of ctivity elicited y the presenttion of the ojectnd in how quickly the sensory response discrimintes mong the ojects 37,66,107. Also, the gol of the prticipnt influences the representtion of these ojects, s the expecttion or importnce of the oject modultes its sensory response 29,33,111,112. How the slience mp links to motor ehviour is n interesting nd importnt issue. Under most circumstnces, the neurophysiologicl correltes of slience closely mtch sccdic ehviour 37,66,107,113. The sme neurons in the superior colliculus (visuomotor neurons) encode oth the slience of the oject nd ny susequent sccde directed to tht oject 41. By contrst, slience nd motor progrmming cn e dissocited in visul neurons in the frontl eye fields 107,114. Perhps neurons tht encode oth signls link slience with motor progrmming. A simple wy to connect slience mpping nd motor progrmming is through the vrile rise-to-threshold model 115 (). In this model, ctivity ccumultes t different rtes (lue nd lck lines) towrds fixed threshold (dotted). Vriility in chieving threshold (shded region) is responsile for the differences in rection times tht re oserved in ehviour. If there re competing progrms, the one tht reches threshold first produces the motor ction. tht trget will pper on one side increses pre-trget ctivity further 30. So, we do not hve good explntion for this effect. Second, we do not know why monkeys show repetition dvntge ut humns produce n lterntion dvntge when tested in the sme wy 34 (see lso REFS 23 27). Prctice might e n importnt fctor in producing this species difference, ecuse humns re typiclly nive when they prticipte in such experiments, wheres monkeys cn perform thousnds of trils dy, five dys week, for mny months. Indeed, sufficient prctice eventully elimintes the lterntion dvntge in humn prticipnts 35 ; perhps fter even more prctice, repetition dvntge would emerge in its plce. Visul serch In the lst exmple, we descried previous tril effects tht occur relily in single-cell ctivity when simple two-lterntive choice sccde tsk is implemented. Most studies tht explore humn cognition include more thn two potentil trgets, mking it importnt to ssess previous tril effects in more complex tsks. For exmple, in the oddll locliztion tsk, n rry of visul ojects is presented to n oserver who must generte sccde to the odd one (see lso REFS 7,10 13). In the studies descried here, the colour of the serch items differentited the trget from the distrctors, which were red or lue (FIG. 2) (other feture differences such s shpe 37 nd grdients 10 produce similr previous tril effects). The colour tht identified the trget nd the trget s loction were selected rndomly cross consecutive trils. Compring sccdic rection times for ech vrile showed tht neither the solute colour (red versus lue) nor the solute loction of the trget influenced performnce. However, previous tril effects were otined: two originting from the colour of the trget (sme versus different trget colour) nd one originting from the loction of the trget (sme versus different trget loction). Colour of the trget. The colour of the trget cross consecutive trils produces two distinct previous tril effects: priming of pop-out when the trget colour remins the sme, nd competing motor plns when the trget colour chnges. After descriing the neurophysiologicl correltes of these phenomen, we propose tht oth effects represent different perspectives of the sme picture. When performing the oddll locliztion tsk, monkeys respond fster nd mke fewer errors when the colour of the trget remins the sme cross consecutive trils 37 (FIG. 2). Humns show the sme effect, which is clled priming of pop-out 7,10,42. In the frontl eye fields, priming of pop-out is represented in the neurl signture tht is linked to trget selection. In response to the ppernce of the serch rry, the ctivity of visul neurons in the frontl eye fields increses. At first, the mgnitude of neuron s ctivity is similr whether the trget or distrctor is in its receptive field. Shortly therefter, the neuron increses its ctivity when the trget is in its receptive field, ut decreses its ctivity when distrctor is in its receptive field (trget selection). The colour of the trget on the previous tril ffects how quickly trget selection is chieved: it is fster when the colour of the serch rry remins the sme cross consecutive trils (FIG. 2c; top pnel, lue trce) thn when it chnges (ottom pnel, red trce). This difference ecomes lrger s the numer of repeted trils increses 38 (FIG. 2d, ehviour; FIG. 2e, neurl ctivity). When the colour reltionship chnges cross trils, monkeys mke more short-ltency corrective sccdes nd the trjectories of single sccdes re often curved. Both of these effects hve een interpreted s evidence for concurrent progrmming of sccdic motor plns. Short-ltency corrective sccdes (FIG. 3c) occur when NATURE REVIEWS NEUROSCIENCE VOLUME 4 JUNE

4 c d OO SO OS SS Sme loction O S Opposite loction ALL N 1 sme loction N 1 opposite loction Time from trget onset Figure 1 The two-lterntive choice sccde tsk. Averge sccdic rection times in the two-lterntive choice sccde tsk when the trgets ppered t the sme or the opposite loction s the previous tril. Averged spike-density wveforms of visuomotor neuron in the intermedite lyers of the superior colliculus, showing pre-trget ctivity when the trget in the previous tril ppered in the response field of the neuron (lue) or t the opposite position (red). c Previous tril effects ccumulte cross multiple consecutive trils. Sccdic rection times continue to decrese s the numer of repeted trils increses (left) nd this further decrese in sccdic rection time is ssocited with further increses in pre-trget ctivity (right). N, current tril; N 1, one tril ck; N 2, two trils ck. d Left, correltion etween sccdic rection time nd pre-trget ctivity for single neuron; right, distriution of correltion coefficients etween pre-trget ctivity nd sccdic rection times for every neuron in the smple. Blue rs represent correltions tht chieved sttisticl significnce (p < 0.05). ALL, ll loctions. Pre-trget ctivity (spikes s 1 ) O = Opposite S = Sme 40 N 2 N 1 N N 2 N 1 N Tril sequence Tril sequence Numer of neurons Pre-trget ctivity (spikes s 1 ) Correltion coefficient 50 spikes s SS OS SO OO ALL the prticipnt initites sccde towrds the distrctor efore inititing second sccde to the trget. The importnt feture of the second, corrective sccde is tht it must hve een progrmmed t the sme time s the first sccde ecuse its rection time is shorter thn the theoreticl minimum time tht is required to pln nd initite sccde 39,40,42 (see lso REFS 46 48). By contrst, curved sccdes re single sccdes tht do not follow stright trjectory, ut tht re rched. In visul serch, these curved sccdes re rre, ut they occur most frequently when monkeys incorrectly generte sccde to distrctor. In this cse, the sccde s trjectory ends towrds the trget 39,49 (see lso REFS 50 53) (FIG. 3d). S O The distinct ptterns of neurl ctivity ssocited with concurrent progrmming of sccdic gols re shown in FIG. 3. FIGURE 3 shows the ctivity of neuron when the trget ppers in its response field nd stright sccde ws initited to its loction. There is one distinct urst, corresponding to motor-relted ctivity. FIGURE 3 represents the ctivity of the sme neuron when stright sccde ws initited to trget djcent to its response field. In this instnce, there is no motor urst ecuse the sccde ws not initited into the response field of the neuron. Compre these exmples, in which the ssocited ehviour showed no concurrent sccdic plns, with instnces in which it did (to fcilitte these comprisons, the ctivity shown in FIG. 3 is reproduced). FIGURE 3c shows the ctivity of the sme neuron when second, short-ltency sccde ws directed to the trget (inside the neuron's response field) fter the first sccde ws initited to distrctor (outside the neuron's response field). In this cse, the ctivity of the neuron encoding the gol of the second sccde ws elevted when the first sccde ws initited (red trce), indicting tht competing motor pln ws present. A similr elevted response ws seen when the trjectory of the sccde (directed elsewhere) ws curved towrds the trget (inside the neuron's response field) (FIG. 3d, lue trce). In support of the ide tht competing motor progrms cuse curved sccdes, rtificilly inducing competing motor progrm through electricl stimultion produces sccdes with trjectories tht re ent towrds the site of stimultion 49. So, whether the colour of the trget chnges from tril to tril hs importnt consequences. When it remins the sme, prticipnts initite response fster nd this priming of pop-out is ssocited with fster trget selection in the frontl eye fields 37. When it chnges, prticipnts produce responses tht indicte tht competing motor progrms were plnned, nd these concurrent motor progrms re seen in the slience mps of the superior colliculus 40,49. Up to now, these previous tril effects hve een treted seprtely. However, priming of pop-out nd concurrent motor progrms might represent different spects of the sme picture; tht is, differences in the reltive slience of the trget tht originte from mintining or switching tsk set The colour tht defines the trget on hlf of the trils defines the distrctors on the remining trils, ecuse the colour of the trget (nd distrctors) is selected rndomly nd only two colours re used (short runs of trils in which the trget s feture remins the sme hve een used in some studies 37 ). Even though prticipnts cn flexily choose which oject is the trget on ech tril, it is esier for them to mke this decision when the colour does not chnge (mintining tsk set) thn when it does chnge (switching tsk set). So, when the colour of the trget remins the sme cross consecutive trils, the trget s slience increses nd the distrctors slience decreses, which llows prticipnts to respond more efficiently. Consistent with this explntion, the dvntge of keeping the colour the sme grows s the numer of trils increses 10,37 (FIG. 2d,e), nd this is ssocited with n incresingly exggerted neurl representtion of the 4 JUNE 2003 VOLUME 4

5 c Consecutive trils 50 spikes s 1 Trget discrimintion time Sme trget colour Different trget colour Sme colour, different loction Time from onset of serch rry (ms) Different colour, sme loction d Activity (spikes s 1 ) Trget in RF Sme colour Different colour Trils since colour chnge No. of trils since colour chnge 2 4 Distrctor in RF Figure 2 The oddll locliztion tsk. Illustrtion of the tsk. In the second serch rry, the colour of the trget is the sme s in the first, ut the loction hs chnged; in the third rry the loction of the trget remins the sme, ut the colour hs chnged. Grey ellipses represent neuron s response field. Averge sccdic rection times when the colour of the trget remined the sme (lue) or chnged (red) cross consecutive trils. c Averged spike density wveforms of single neuron in the frontl eye fields, showing previous tril effects when the colour of the trget remined the sme cross consecutive trils (top) nd when it chnged (ottom). Arrows show differences in trget discrimintion time. Grey lines show ctivity when distrctor ws in the neuron s response field (RF). d,e Chnges in sccdic rection time (d) nd neurl ctivity (e) s the numer of trils cross which the trget colour stys the sme increses. Modified, with permission, from REF. 37 (2002) Society for Neuroscience. e 240 trget nd incresingly ttenuted neurl representtions of the distrctors in the frontl eye fields 37. A similr pttern of improvement hs een otined in tsk-switching studies 17,18. Alterntively, when the colour of the trget chnges cross consecutive trils, the slience of the distrctors is ccentuted ecuse the sme feture defined the trget on the previous tril, which cuses the distrctors to compete with the trget for selection 28. Consistent with this explntion, llowing prticipnts to mintin the sme tsk set elimintes the interference of distrctor in vrint of the oddll serch tsk 54. Viewing priming of pop-out nd concurrent motor plns s chnges in the reltive slience of the trget tht originte from mintining or switching tsk set provides succinct wy to explin the different effects tht rise from the colour of the trget on the previous tril. Loction of the trget. Chnging the loction of the trget cross consecutive trils lso produces previous tril effects. Monkeys respond more slowly when the trget ppers t the sme loction s in the previous tril thn when it ppers t different loction 37 (FIG. 4).In the frontl eye fields, this chnge in ehviour is reflected in delyed trget selection when consecutive trgets pper in the sme position (FIG. 4). Bichot nd Schll 37 interpreted this loction-sed slowing s inhiition of return, consistent with previous empiricl findings nd theoreticl developments 23 25, Inhiition of return descries the tendency of oservers to e slower to reorient to previously ttended loction thn to orient to new loction 58 60, which encourges them to explore new loctions in their environment 56. In ddition to its importnt role in orienting sptil ttention, inhiition of return provides us with the opportunity to explore the consequences of the previous event (rther thn the previous ction) y using cue trget tsk insted of the oddll serch tsk. In this tsk, the previous tril is replced y cue to which no response is required. Ech tril egins with prticipnts mintining their gze t centrl loction (FIG. 5). A rief flsh of light (the cue) then ppers t one loction in the visul periphery, followed y second visul oject, the trget, ppering t either the sme or different loction. In mny studies, prticipnts indicte the sptil loction t which the trget ppered, either with mnul utton press (for exmple, left utton press for left trget) or y inititing sccde to the trget s loction 60,61. When the time etween the onset of the cue nd trget exceeds ~200 ms, nd the cue does not predict the upcoming loction of the trget, prticipnts respond more slowly when the cue nd trget pper t the sme loction 56,62 thn when they pper t different loctions. Therefore, the ppernce of cue lone is sufficient to produce inhiition of return. Wht influence does the cue hve? FIGURE 5 shows the ctivity of single neuron in the superior colliculus during this tsk. When the trget ppers in the neuron s response field nd the cue ppers to the opposite side (red line), two peks of ctivity occur, the first representing the sensory response to the trget (herefter referred to s trget-relted) nd the second representing the motor urst tht precedes the sccde. By contrst, when oth the cue nd the trget pper in the neuron s response field (lue line) there re three peks of ctivity: the first pek represents the sensory response to the cue, the second the sensory response to the trget, nd the third the motor urst. Compring these conditions revels two consequences of the cue when it ppers on the sme side s the trget: the firing rte of the neuron is elevted immeditely fter the cue (rrow) nd the trget-relted response is ttenuted (highlighted with the yellow r). These re conflicting signls; the elevted firing rte etween the cue nd the trget indictes tht the neuron is more excitle 30,33,63 ut the ttenuted trget-relted ctivity indictes tht the neuron is receiving weker incoming visul signl (see REFS 64,65 for similr findings in the superficil NATURE REVIEWS NEUROSCIENCE VOLUME 4 JUNE

6 SPATIAL REFERENCE FRAMES A reference frme descries set of coordintes tht is used to define where n oject is locted in spce. In retinocentric reference frme ojects re mpped in retinl coordintes. In n environmentl sed (or llocentric) reference frme ojects re mpped in worldsed coordintes. Stright sccde into RF Stright sccde out of RF c Short-ltency second sccde d Curved sccde Time from sccde strt (ms) Figure 3 Competing motor plns., Behviourl nd neurl correltes of trils when no concurrent motor plns were oserved. A single stright sccde is generted into the response field (RF, grey ellipse) of the neuron (, lck line) or to the djcent loction outside the neuron s response field (, grey line). c,d Behviourl nd neurl correltes of trils when concurrent motor plns were oserved. c Shortltency second sccdes, in which the second concurrently progrmmed sccde ws initited into the response field of the neuron (red line). d Curved sccdes with the trjectory ent towrds the response field of the neuron (lue line). Arrows indicte the elevted neurl ctivity ssocited with the concurrent motor pln. The grey line in c nd d is reproduced from for comprison. Modified, with permission, from REFS 40,49 (2002) The Americn Physiologicl Society. lyers of the superior colliculus nd posterior prietl cortex). In the fce of these conflicting signls, the monkeys respond more slowly when the cue nd trget pper t the sme loction, which indictes tht the trget-relted ctivity domintes the ehviour. This outcome mkes sense ecuse the trget-relted signl is 100 spikes s 1 the lst signl received efore the ction is initited (prticipnts initite sccde when the trget ppers) nd, therefore, is crucil in llowing the neuron to rech threshold ctivity for the motor ction (BOX 2). Consistent with this interprettion, trget-relted ctivity correltes closely with sccdic rection times on tril-y-tril sis (less ctivity is ssocited with slower response times 66 ). Sccdic rection times do not show similr reltionship with the elevted ctivity efore the trget 67. Compring the neurophysiologicl correltes of inhiition of return tht originte from visul serch (delyed trget selection) nd from the cue-trget tsk (ttenuted trget-relted ctivity) shows tht the neurophysiologicl mechnisms responsile for inhiition of return might differ depending on the tsk used to produce it. This is not n unexpected finding, s there is ccumulting ehviourl evidence tht inhiition of return might originte from mny mechnisms, ecuse smll chnges to the cue trget tsk modify its chrcteristics. For instnce, sking prticipnts to respond with different effectors (eye versus hnd) chnges the mount of time etween cue nd trget tht is needed to produce inhiition of return 60,68 nd the SPATIAL REFERENCE FRAME in which inhiition of return is encoded (retinocentric versus environmentl 69 ; see lso REFS 70 72). Even when effector differences re disregrded, chnging whether prticipnts detect the onset of the trget or indicte feture of the trget (such s its colour) lso chnges when inhiition of return is oserved 73 nd, in some instnces, cn chnge whether inhiition of return occurs t ll Clerly, much reserch is required efore we fully understnd the mechnisms of inhiition of return nd we should e cutious in extending findings etween studies. Focusing on the differences cross studies ignores one feture tht is common to oth of the physiologicl exmples inhiition of return origintes from the diminished slience of the trget (even though it is cused y different mechnisms). Although this does not explin ll fcets of inhiition of return 74 76,it is consistent with computtionl models of ttention, which propose tht inhiition of return decreses the slience of the oject nd llows new loctions in the visul world to e explored Conclusions As we hve shown, previous tril effects cn e produced in vrious tsks nd cn originte from different neurophysiologicl mechnisms. One simple wy to integrte these different effects is to consider how the previous tril chnges the slience of the trget, or the gol of the ction, on sptil mp (BOX 2). In ll instnces, the trget s representtion is modified y the previous tril, incresing or decresing its representtion on the slience mps of the frontl eye fields or superior colliculus. Consider first the repetition dvntge in the twolterntive choice sccde tsk. In this instnce, incresed pre-trget ctivity of neurons in the superior colliculus enhnces the reltive slience of tht region 6 JUNE 2003 VOLUME 4

7 Sme loction Different loction on the mp, which llows the sccde to e initited fster when the trget ppers t tht loction. Likewise, priming of pop-out nd competing motor plns might reflect the reltive sliences of the trget nd distrctors. When the slience of the trget is high nd the slience of the distrctors is low ecuse prticipnts hve mintined the tsk set, priming of pop-out is produced. By contrst, when the slience of the trget is low nd the slience of the distrctors is high ecuse prticipnts hve switched tsk set, the distrctors compete with the trget nd cn influence the trjectory of Cue sme Cue opposite Time Cue sme Fixtion Cue Fixtion Trget 250 spikes s 1 50 spikes s 1 Sme trget loction Different trget loction Time from onset of serch rry (ms) Figure 4 Effects of trget loction in visul serch tsk. Averge sccdic rection time when the trget remined t the sme loction nd when it chnged loction from the previous tril. Averged spike-density wveforms of visul neurons in the frontl eye fields tht show differences in trget selection when the consecutive trget ppered t the sme loction (top pnel, lue) nd when they ppered t different loctions (ottom pnel, red). Arrows indicte differences in trget discrimintion time nd the grey lines show ctivity when the trget ws not in the neuron s response field. Modified, with permission, from REF. 37 (2002) Society for Neuroscience. Cue opposite Time from trget's ppernce (ms) Figure 5 Inhiition of return. Design of cue trget tsk used to explore inhiition of return. Grey ellipses represent neuron s response field. Averged spike-density wveform of visuomotor neuron in the superior colliculus, reveling the ttenuted trget-relted response (shded in yellow) when the cue ppered t the sme loction s in the previous tril (in lue) compred with when it ppered in different loction (in red). the sccde or result in the rpid initition of second sccde. Finlly, inhiition of return origintes from delyed trget selection or from ttenuted trget-relted ctivity, depending on the tsk used to produce it, which cuses the slience of the trget to e lower. Becuse the trget drives the motor pln in ll of the tsks descried in this review, modifictions of the slience of the trget lter how quickly threshold for chieving n ction cn e chieved nd produce the chnges in ehviour tht we ssocite with previous tril effects. This review does not descrie ll previous tril effects tht hve een reported. By focusing on the neurophysiologicl correltes of previous tril effects in oculomotor structures, we hve not shown why the extrinsic inputs into these structures hve een modified. For instnce, the ttenuted trget-relted processing in inhiition of return is seen erly in sensory processing, for exmple in the superficil lyers of the superior colliculus tht receive inputs from the retin nd erly visul res 64,66. Similr ttenuted processing of visul ojects hs een oserved in rin structures tht re more closely tied to visul perception: for instnce, previous exposure to visul oject decreses its neurl representtion in inferior temporl neurons the next time it is presented (see lso REFS 84 86). How this chnge in neurl ctivity trnsltes into ehviour is uncler. It might e responsile for repetition priming (the tendency to respond fster to n oject when it is repeted 82,87 89 ) or for negtive priming (the tendency to respond more slowly to n oject when it is repeted 9,14,15 ). Perhps the prmeters of the tsk used to explore previous events chnge the wy the sme signl is trnslted in the slience mps This is n open question for future reserch. Returning to the nlogy descried in the introduction, single picture ccurtely cptures one instnt, ut does not revel the events involved in shping tht moment. For instnce, our friend wering lipstick nd the tir ws not entirely responsile for his unusul ppernce. Like single photogrphs, cognitive processes re lso influenced y previous events, in which prticipnts might respond more quickly or slowly, or the trjectory of the response might e ltered. We hve discussed how these chnges in ehviour re reflected in the ctivity of single neurons in the slience mps of the frontl eye fields nd superior colliculus, wherein the previous tril increses or decreses the slience of the trget. Our gol ws to review exmples of previous tril effects in the oculomotor system, to show tht the neurl imprints involved in producing these previous tril effects cn e relily mesured, nd to stimulte further reserch in this re. Ultimtely, history might prove this review to e preliminry in its content. Even so, it cnnot undo one cler concept summrized in this rticle preceding events or ctions shpe the outcome of ech tril nd these previous tril effects cn e relily oserved in the ctivity of single neurons tht re involved in encoding the response. NATURE REVIEWS NEUROSCIENCE VOLUME 4 JUNE

8 1. Cttell, J. M. The time tken up y cererl opertions, prts 1 & 2. Mind 11, (1886). 2. Cttell, J. M. The time tken up y cererl opertions, prt 3. Mind 11, (1886). 3. Cttell, J. M. The time tken up y cererl opertions, prt 4. Mind 11, (1887). References 1 3 re clssic rticles tht descrie Cttell s systemtic nd clever ttempts to dissocite the components of rection time. 4. Posner, M. J. & Mitchell, R. F. Chronometric nlysis of clssifiction. Psychol. Rev. 74, (1967). 5. Luce, R. D. Response Times: Their Role in Inferring Elementry Mentl Orgniztion (Oxford Univ. Press, Oxford, 1986). 6. Bertelson, P. Sequentil redundncy nd speed in seril two-choice responding tsk. Q. J. Exp. Psychol. 13, (1961). 7. Brvo, M. J. & Nkym, K. The role of ttention in different visul-serch tsks. Percept. Psychophys. 51, (1992). 8. Gupt, P. & Cohen, N. J. Theoreticl nd computtionl nlysis of skill lerning, repetition priming, nd procedurl memory. Psychol. Rev. 109, (2002). 9. My, C. P., Kne, M. I. & Hsher, L. Determinnts of negtive priming. Psychol. Bull. 118, (1995). 10. Mljkovic, V. & Nkym, K. Priming of pop-out I. Role of fetures. Mem. Cogn. 22, (1994). 11. Mljkovic, V. & Nkym, K. Priming of pop-out II. Role of position. Percept. Psychophys. 58, (1996). 12. Mljkovic, V. & Nkym, K. Priming of pop-out III. A shortterm implicit memory system eneficil for trget selection. Vis. Cogn. 7, (2000). 13. Remington, R. J. Anlysis of sequentil effects in choice rection times. J. Exp. Psychol. 82, (1969). 14. Tipper, S. P. The negtive priming effect: inhiitory priming y ignored ojects. Q. J. Exp. Psychol. A 37, (1985). 15. Tipper, S. P. Does negtive priming reflect inhiitory mechnisms: review nd integrtion of conflicting views. Q. J. Exp. Psychol. A 54, (2001). 16. Willinghm, D. B., Nissen, M. J. & Bullemer, P. On the development of procedurl knowledge. J. Exp. Psychol. Lern. Mem. Cogn. 15, (1989). This pper elegntly demonstrtes the development nd the role of unconscious processes in sequence lerning. 17. Allport, A. & Wylie, G. in Control of Cognitive Processes: Attention nd Performnce XVIII (eds Monsell, S. & Driver, J. S.) (MIT Press, Cmridge, Msschusetts, 2000). 18. Gilert, S. J. & Shllice, T. Tsk switching: PDP model. Cognition 44, (2002). This pper provides simple computtionl model of tsk switching nd comprehensive review of the tsk-switching literture. 19. Pshler, H. in Control of Cognitive Processes: Attention nd Performnce XVIII (eds Monsell, S. & Driver, J. S.) (MIT Press, Cmridge, Msschusetts, 2000). 20. Rogers, R. D. & Monsell, S. Costs of predictle switch etween simple cognitive tsks. J. Exp. Psychol. Gen. 124, (1995). 21. Kim, N., Ivry, R. B. & Roertson, L. C. Sequentil priming in hierrchiclly orgnized figures: effects of trget level nd trget resolution. J. Exp. Psychol. Hum. Percept. Perform. 25, (1999). 22. Roertson, L. C. Attentionl persistence for fetures of hierrchicl ptterns. J. Exp. Psychol. Gen. 125, (1996). 23. Tnk, Y. & Shimojo, S. Loction vs feture: rection time revels dissocition etween two visul functions. Vision Res. 36, (1996). This pper shows how two different modes of response (responding to the loction of the trget or feture of the trget) reverse the influence of the previous tril. 24. Tnk, Y. & Shimojo, S. Repetition priming revels sustined fcilittion nd trnsient inhiition in rection time. J. Exp. Psychol. Hum. Percept. Perform. 26, (2000). 25. Tylor, T. L. & Donnelly, M. P. Inhiition of return for trget discrimintions: the effect of repeting discriminted nd irrelevnt stimulus dimensions. Percept. Psychophys. 64, (2002). 26. Kiry, N. H. Sequentil effects in two-choice rection time: utomtic fcilittion or sujective expectncy? J. Exp. Psychol. Hum. Percept. Perform. 2, (1976). 27. Soetens, E. Loclizing sequentil effects in seril choice rection time with the informtion reduction procedure. 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This pper shows tht pre-trget ctivity in the superior colliculus is modulted y the likelihood tht trget will pper in its response field. 34. Munoz, D. P., Au, C. S. & Dorris, M. C. Effects of previous history on sccdic rection times. Soc. Neurosci. Astr. 27, (2001). 35. Soetens, E., Boer, L. C & Hueting, J. E. Expectncy or utomtic fcilittion? Seprting sequentil effects in twochoice rection time. J. Exp. Psychol. Hum. Percept. Perform. 11, (1985). 36. Bichot, N. P. & Schll, J. D. Effects of similrity nd history on neurl mechnisms of visul selection. Nture Neurosci. 2, (1999). This pper ws the first to show the neurl correlte of conjunction serch. 37. Bichot, N. P. & Schll, J. D. Priming in mcque frontl cortex during popout visul serch: feture-sed fcilittion nd loction-sed inhiition of return. J. Neurosci. 22, (2002). This pper descries the neurophysiologicl correltes of priming of pop-out in the frontl eye fields. 38. Keller, E. L. & McPeek, R. M. Neurl dischrge in the superior colliculus during trget serch prdigms. Ann. NY Acd. Sci. 956, (2002). 39. McPeek, R. M. & Keller, E. L. Short-term priming, concurrent processing, nd sccde curvture during trget selection tsk in the monkey. Vision Res. 41, (2001). 40. McPeek, R. M. & Keller, E. L. Superior colliculus ctivity relted to concurrent processing of sccde gols in visul serch tsk. J. Neurophysiol. 87, (2002). This pper shows tht evidence of concurrent motor progrmming in ehviour is ssocited with competing motor plns in the ctivity of superior colliculus neurons. 41. McPeek, R. M. & Keller, E. L. Sccde trget selection in the superior colliculus during visul serch tsk. J. Neurophysiol. 88, (2002). 42. McPeek, R. M., Mljokovic, V. & Nkym, K. Sccdes require focl ttention nd re fcilitted y short-term memory system. Vision Res. 39, (1999). 43. Schll, J. D. & Hnes, D. P. Neurl sis of sccde trget selection in frontl eye field during visul serch. Nture 366, (1993). The first pper to show the correlte of trget selection nd how competing ojects interct in the slience mp of the frontl eye fields. 44. Schll, J. D. & Thompson, K. G. Neurl selection nd control of visully guided eye movements. Annu. Rev. Neurosci. 22, (1999). An excellent review rticle descriing trget selection nd visul msking. 45. Schll, J. D., Hnes, D. P., Thompson, K. G. & King, D. J. Sccde trget selection in frontl eye field of mcque. I. Visul nd premovement ctivtion. J. Neurosci. 15, (1995). 46. Becker, W. & Jurgens, R. An nlysis of the sccdic system y mens of doule step stimuli. Vision Res. 19, (1979). 47. Theeuwes, J., Krmer, A. F., Hhn, S., Irwin, D. E. & Zelinsky, G. J. Influence of ttentionl cpture on oculomotor control. J. Exp. Psychol. Hum. Percept. Perform. 25, (1999). 48. Theeuwes, J., Krmer, A. F., Hhn, S. & Irwin, D. E. Our eyes do not lwys go where we wnt them to go: cpture of the eyes y new ojects. Psychol. Sci. 9, (1998). 49. Mc Peek, R. M., Hn, J. H. & Keller, E. L. 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Neurl control of voluntry movement initition. Science 274, (1996). This study tests different models of rection time nd shows tht the vrile rise-to-threshold model est fits the neurophysiologicl dt. Acknowledgements The uthors gretly pprecite helpful comments from R. McPeek on n erlier version of this rticle. J.F. is supported y postdoctorl fellowship from the Nturl Sciences nd Engineering Reserch Council of Cnd. D.M. is supported y the Cnd Reserch Chir Progrm. NATURE REVIEWS NEUROSCIENCE VOLUME 4 JUNE