Neural correlates of decision variables in parietal cortex

Transcription

1 Neurl correltes of decision vriles in prietl cortex Michel L. Pltt & Pul W. Glimcher Center for Neurl Science, New York University, New York, New York 13, USA... Decision theory proposes tht humns nd nimls decide wht to do in given sitution y ssessing the reltive vlue of ech possile response. This ssessment cn e computed, in prt, from the proility tht ech ction will result in gin nd the mgnitude of the gin expected. Here we show tht the gin (or rewrd) monkey cn expect to relize from n eye-movement response modultes the ctivity of neurons in the lterl intrprietl re, n re of primte cortex tht is thought to trnsform signls into eye-movement commnds. We lso show tht the ctivity of these neurons is sensitive to the proility tht prticulr response will result in gin. When nimls cn choose freely etween two lterntive responses, the choices sujects mke nd neuronl ctivtion in this re re oth correlted with the reltive mount of gin tht the niml cn expect from ech response. Our dt indicte tht decision-theoretic model my provide powerful new frmework for studying the neurl processes tht intervene etween senstion nd ction. Neuroiologists hve egun to focus incresingly on the study of sensory±motor processing, ut mny of the models used to descrie these processes remin rooted in the clssic re ex, initilly descried y Descrtes 1 nd lter dvocted y Sherrington 2 s model system for studying the connection etween senstion nd movement. Sherrington, in prticulr, viewed response selection s physicl link etween independent, ntomiclly distinct sensory nd motor systems 2. Until recently, the sensory±motor re ex ws tcitly ccepted y mny physiologists s n pproprite model for descriing the neurl processes tht underlie complex ehviour 3±5. More recent ndings indicte tht, t lest in some cses, the neurl events tht connect senstion nd movement my involve processes other thn clssicl re exive mechnisms 6±9 nd these dt support theoreticl pproches tht hve chllenged re ex models directly 1±13. Reserchers outside physiology hve long rgued for richer models of the sensory±motor process 14±18. These models invoke the explicit representtion of clss of decision vriles, which crry informtion out the environment, re extrcted in dvnce of response selection, id in the interprettion or processing of sensory dt nd re prerequisite for rtionl decision mking 19. Here we descrie forml economic±mthemticl pproch for the physiologicl study of the sensory±motor process, or decision-mking, in the lterl intr-prietl re (LIP) of the mcque rin. Theoreticl tretments of decision mking Although mthemticl pproches to decision-mking propose different formule for identifying the response suject should choose under given set of conditions, nerly ll theories require the decision-mker to hve some knowledge of two environmentl vriles: the gin expected to result from n ction nd the proility tht the expected gin will e relized. The expected vlue theory of Arnud nd Nichole 2, for exmple, proposes tht rtionl decision-mker should multiply expected gin y the proility of gin to estlish n expected vlue for ech course of ction, nd then should choose the option with the highest expected vlue. Although susequent theorists hve proposed different mthemticl comintoril rules tht provide more ccurte models of the decision-mking process, knowledge of the gin expected from response nd the proility of relizing tht gin is still considered to e criticl to the computtion of rtionl choice 19,2,22. Ecologicl iologists 17,18 nd psychologists 14±16 hve lso developed forml models of decision-mking. Most of these models ssume tht nimls mke decisions tht either mximize the rte of energy intke from different options or mtch their rtes of ehviourl responding to the reinforcement rtes otined from different choices. These models propose tht nimls choose on the sis of severl vriles, including the proility of reinforcement 23 nd the mgnitude of reinforcement 24,25 ssocited with different responses. Experimentl evidence indictes tht expected gin nd proility of gin do in uence the choices nimls mke. However, neuroiologicl models of the processes tht connect senstion nd ction lmost never propose the explicit representtion of decision vriles y the nervous system. Most contemporry neurophysiologicl models, prticulrly models of corticl sensory±motor trnsformtions, identify sensory nd motor signls s criticl components, ut they rrely ddress the possiility tht neurl signls my encode dt tht fll outside these two ctegories. Our investigtions hve led us to propose tht decision theory might provide powerful lterntive frmework for studying the sensory±motor process. Our current model could e descried s hving two clsses of inputs: current sensory dt, nd stored representtion of environmentl contingencies. Current sensory dt would re ect the oserver's est estimte of the current stte of the slient elements of the environment. As such, it would e in uenced y stored informtion tht could improve the ef ciency of sensory processing through selective ttention. The second clss of inputs would represent the chooser's ssumptions out current environmentl contingencies, clss of inputs tht detil how n ction ffects the chooser. Decision mking would involve the comintion of post-ttentionl sensory dt with the suject's est estimte of the outcome of ny given ction. These estimtes of environmentl contingencies would then e comined with loss function specifying the vlue of ll possile losses nd gins to the chooser, ccording to decision rule like the one originlly proposed y Arnuld nd Nichole 2 or in susequent re nements of their model 19,21,22. Physiology of sensory±motor integrtion in LIP Although neuroiologists hve not employed decision-theoretic formultions of this type, mny groups hve concluded tht numer of rin res re involved in the processes tht intervene etween senstion nd ction. Prietl re LIP hs een lelled ttentionl 26,27, decision-relted 28 nd motor-preprtory 29±31 y different groups. Our own work indictes tht decision-theoretic models my provide powerful lterntive pproch to the study of sensory±motor processing in prietl cortex 32,33. NATURE VOL 4 15 JULY

2 In one study 34, we ssumed tht ttention cn e treted s conceptully seprle from other elements of the decision-mking process. We used two tsks tht independently controlled oth the loction of sccdic trget nd the loction nd ehviourl relevnce of distrctor. In oth tsks, monkey initilly xted centrl stimulus, nd then two eccentric stimuli were illuminted, one ove nd one elow the centrl stimulus. A chnge in the colour of the centrl stimulus identi ed one eccentric stimulus s the eventul sccdic trget nd the other s distrctor. In one tsk, the distrctor ws highly relevnt ecuse c Trget onset 5 1, 1,5 ms 5 n = Expected gin rtio Regression slope * * * * * * * * * * * EV LV EC LC PR PO CH99322 CH99322 Figure 1 Modultion of neuronl ctivity y expected gin. The volume of juice delivered for ech response ws vried cross locks of d sccde trils., Firing rte of n intrprietl neuron on trils instructing gze shifts into the response eld, verged in 1 ms ins nd synchronized, t verticl line, on trget onset. Thick lck line, expected gin rtio ˆ :75 (n ˆ 48); thick grey line, expected gin rtio ˆ :25 (n ˆ 37). Rster pnels show spike times during the rst 2 high-gin (drk grey) nd rst 2 low gin (light grey) trils. Pnels show individul trils in sequentil order from top to ottom. Arrows plot, successively, men times of instruction onset, centrl xtion stimulus offset nd sccde onset during high- (lck rrow) nd low- (grey rrow) gin locks. Strs indicte 1-ms ins in which ring rte ws signi cntly different in the high-gin lock thn in the low-gin lock (t-test, P, :5)., Men ring rte (6 s.e.) during ech intervl plotted ginst expected gin rtio, for ll trils instructing gze shifts into the neuronl response eld. Lines indicte est- t liner regressions through the rw dt. c, Men (6 s.e.) regression slope for expected gin (circles) nd the instructed movement (tringles), plotted ginst time (n ˆ 4 neurons). Intervls: EV, erly ; LV, lte ; EC, erly ; LC, lte ; PR, pre-movement; PO, post-movement. offset of this stimulus signlled the niml to initite sccde to the trget; in the second tsk the distrctor ws completely irrelevnt, ecuse offset of the centrl stimulus signlled the niml to initite the sccde. Although intrprietl neurons were more ctive on locks of trils in which stimulus served s sccdic trget thn on locks of trils in which the sme stimulus served s distrctor, none of the neuronl responses distinguished etween ehviourlly relevnt nd irrelevnt distrctors. We took this nding s preliminry evidence tht ctivity in re LIP does not prticipte in sensory-ttentionl processing ut is correlted with either outcome contingencies, gin functions, decision outputs or motor plnning, ll processes tht our decision-theoretic pproch indictes re criticl in choice ehviour. Experimentl design Here we exmine whether decision-theoretic model might revel link etween the ctivity of re LIP neurons nd the choices nimls mke in n oculomotor tsk. In the rst experiment (experiment 1; Figs 1, 2), we monitored the ctivity of single intrprietl neurons while nimls performed d sccde trils, in which chnge in the colour of centrlly locted xtion stimulus instructed sujects to mke one of two possile eyemovement responses in order to receive juice rewrd. Before this stimulus chnged colour, the rewrded movement ws miguous. In successive locks of trils, we vried either the volume of juice delivered for ech instructed response (expected gin) or the proility tht ech possile response would e instructed (outcome proility), while holding ll sensory signls nd motorrelted vriles constnt. This llowed us to test whether ny portion of the vrition in re LIP spike rtes oserved under these conditions ws correlted with vritions in the decision vriles we mnipulted. In the second experiment (experiment 2; Figs 3, 4), nimls were rewrded for choosing either of two possile eye-movement responses. In sequentil locks of trils, we vried the gin tht could e expected from ech possile response nd then used the frequency with which the niml chose ech response s n estimte of the sujective vlue of ech option. This permitted us to test whether neurl ctivity in re LIP ws correlted with ehviourlly derived estimte of response vlue. Our dt indicte tht some of the vrition in the LIP ctivity ws, in fct, correlted with economic decision vriles nd tht these vriles in uenced the choices mde y our niml sujects nd neurl ctivity in similr mnner. Decision vriles nd LIP spike rtes Figure 1 shows the ctivity of n intrprietl neuron on ly identicl d sccde trils during which the monkey ws instructed to shift gze into the neuronl response eld for juice rewrd. When, in one lock of trils (thick lck line),.26 ml of juice ws delivered, this neuron ws more ctive thn when the sme movement ws mde in response to the sme disply ut during lock (thick grey line) in which only.9 ml of juice ws delivered. This neuron ws studied while expected gin ws systemticlly vried cross seven locks of trils, nd ehviourl performnce ws mintined t 91% correct. To quntify the effects of these mnipultions on the ctivity of this neuron, we computed verge ring rtes in six 2-ms epochs during ech tril (erly : ±2 ms fter the onset of the two response trgets; lte : 2± ms efore the centrl light-emitting diode (LED) chnged colour; erly : ±2 ms fter the centrl LED identi ed the movement tht would e reinforced; lte : 2± ms efore the commnd to initite the movement; pre-movement: ±2 ms efore sccde onset; post-movement: ±2 ms fter sccde onset). Figure 1 shows the ring rte of this neuron (men 6 s:e:) s function of the gin (in ml of juice) expected for movement into the response eld, divided y the sum of the 234 NATURE VOL 4 15 JULY

3 Tle 1 Percentges of recorded neurons showing signi cnt correltions etween ring rte nd expected gin, outcome proility or estimted vlue Decision vrile / xtion* / xtion* /* /* Pre-movement Post-movement Totl... Expected gin 27.5% 32.5% 4% 27.5% 3% 15% 62.5% (17.5%) (15%) (27.5%) (62.5%) (72.5%) (65%) (87.5%) Outcome proility 35% 35% 4% 15% 3% 15% 75% (1%) (1%) (4%) (1%) (95%) (95%) (1%) Estimted vlue 28% 17% 28% 19% 19% 25% 56% (6%) (28%) (47%) (67%) (67%) (69%) (89%)... Ech entry indictes the percentge of cells in ech experiment showing signi cnt (P, :5) modultions in ring rte during ech intervl. Entries in prentheses indicte the percentge of cells tht showed signi cnt modultions in ring rte y the movement ctully mde y the niml. Totl percentges indicte the percentge of neurons showing signi cnt modultion in ring rte during ny intervl. Asterisks identify the nmes of intervls mesured in experiment 2 (erly xtion, lte xtion, erly, lte ). gin (in ml) ville from oth possile movements, for ll those trils in which the niml shifted gze to the trget inside the response eld of the neuron. The ring rte of this intrprietl neuron ws correlted with this expected gin rtio erly in the trils (erly, r ˆ :432, P, :1; lte, r ˆ :372, Trget onset 5 1, 1,5 ms n = Outcome proility c Regression slope ** * * * * * n = 2 EV LV EC LC PR PO CH99215 CH99215 Figure 2 Modultion of neuronl ctivity y outcome proility. The proility tht ech response would e instructed ws vried cross locks of d sccde trils., Firing rte of n intrprietl neuron on trils instructing gze shift into the response eld, s in Fig. 1. Thick lck line, outcome proility ˆ :8 (n ˆ 77); thick grey line, outcome proility ˆ :2 (n ˆ 26)., Men ring rte (6 s.e.) during ech intervl plotted ginst outcome proility, for ll trils instructing gze shifts into the neuronl response eld. c, Men (6 s.e.) regression slope for outcome proility (circles) nd the instructed movement (tringles) plotted ginst time (n ˆ 2 neurons). P, :1; erly, r ˆ :217, P, :1), ut lter in the trils, round the time of the movement, ring rte nd expected gin rtio were uncorrelted. These dt indicte temporl shift in the informtion encoded y this neuron, from expected gin erly in trils to the movement mde y the niml t the end of trils. On these sme trils, movement mplitude (r ˆ 2 :55, P. :322), movement ltency (r ˆ :16, P. :767) nd movement velocity (r ˆ :2, P. :718) were uncorrelted with expected gin. Ech of 4 intrprietl neurons recorded from the rins of three monkeys ws tested in 3±7 locks of trils (men ˆ 4:7) in which the gin ssocited with ech of the two trget LEDs ws different. For ech neuron, correct trils were sorted into two groups sed on whether the d movement ws into or out of the response eld. For ll trils in which the suject shifted gze towrds the response- eld trget, we nlysed the reltionship etween ring rtes computed during ech intervl descried ove nd four vriles: expected gin; the mplitude of ech sccde; the verge velocity of ech sccde; nd the ltency of ech sccde. We used multiple regression nlysis to determine which portion of ring-rte modultion could e uniquely ttriuted to chnges in expected gin independently of chnges in ny of the three remining movementrelted vriles. For comprison, second multiple regression nlysis ws performed to determine the degree to which the ring rte of ech neuron ws uniquely in uenced y which movement the suject ws d to mke, fter correcting for the effects of expected gin, movement mplitude, movement ltency nd movement velocity. The slopes generted y the multiple regression nlyses were used s n index of how strongly chnges in expected gin modulted the ctivtion of intrprietl neurons, independently of chnges in movement mplitude, ltency nd velocity. Figure 1c shows the men regression slope (6 s.e.) for 4 intrprietl neurons for expected gin (circles); the men slopes for the instructed movement (tringles) re provided for comprison. The regression slopes for expected gin were signi cntly greter thn zero (single-smple t-test, P, :5) during the erly nd lte intervls; expected gin strongly modulted the ctivtion of the popultion of intrprietl neurons erly in trils, efore the identi ction of the rewrded movement. After the rewrded movement ws identi ed, however, the ctivtion of the intrprietl popultion ws strongly modulted y the instructed movement, ut not y expected gin. Tle 1 shows the percentges of neurons in this smple tht were signi cntly modulted y expected gin during ech intervl, with the percentges of neurons signi cntly modulted y the instructed movement in ech intervl provided in prentheses for comprison. Overll, 62.5% of prietl neurons crried sttisticlly signi cnt informtion out expected gin t some point during the tril, nd 87.5% of neurons crried sttisticlly signi cnt informtion out which movement ws ctully mde. These dt indicte tht the ctivtion of the intrprietl neuronl popultion is correlted with expected gin rtio, prticulrly during periods of uncertinty erly in trils when decision vriles might e importnt in formulting movement pln. NATURE VOL 4 15 JULY

4 Figure 2 shows the modultion of the ctivity of n intrprietl neuron y chnges in outcome proility during ly identicl d sccde trils. When sccde into the response eld ws instructed with proility of.8 (thick lck line), the neuron ws more ctive thn when n equivlent movement ws instructed with proility of.2 (thick grey line). This neuron ws studied while outcome proility ws vried cross seven locks of trils, nd ehviourl performnce ws mintined t 85% correct. Figure 2 shows the ring rte of this neuron (men 6 s:e:) s function of outcome proility during ech of the six mesured epochs, for ll trils on which the niml ws instructed to shift gze to the response eld of the neuron. During the erly (r ˆ :47, P, :1), lte (r ˆ :349, P, :1), erly (r ˆ :242, P, :1), lte (r ˆ :131, P, :12) nd pre-movement intervls (r ˆ :116, P, :27), ring rte incresed with increses in outcome proility. Movement mplitude (r ˆ :56, P. :291), ltency (r ˆ 2 :98, P. :61) nd velocity (r ˆ :7, P. :183) were not correlted with outcome proility. The ctivity of this neuron ws thus correlted with the proility tht the niml would e instructed to choose ech response, independent of the movement ctully mde y the niml. We studied the effects of vrying outcome proility cross 5±7 locks of trils (men ˆ 6:7) on 2 intrprietl neurons in two monkeys. Overll, 75% of the intrprietl neurons in our smple crried signi cnt informtion out outcome proility t some point during the tril, while ll 2 neurons crried signi cnt informtion out which movement ws ctully mde (Tle 1). Figure 2c shows the men (6 s.e.) regression slopes for outcome proility ( lled circles) nd the instructed movement ( lled tringles) for our popultion. The regression slopes for outcome proility were signi cntly greter thn zero during the erly, lte nd erly intervls (single-smple t-tests, P, :5). The movement mde y the niml signi cntly modulted neuronl ctivity in this popultion only fter the identi ed the reinforced movement (lte, pre-movement nd post-movement intervls, single-smple t-tests, P, :5). The modultions induced y chnges in outcome proility were very similr to those evoked y chnges in expected gin nd support the ide tht outcome proility in uences decision processes efore the colour of the xtion stimulus identi es the reinforced movement. Response vlue nd LIP neurl ctivity The results of experiment 1 show tht chnges in either the gin expected from prticulr response or the proility tht prticulr response will e required modulte the ctivity of intrprietl neurons. This is true even when ll the nd motor events ssocited with ech tril re the sme. In experiment 1, however, we were limited in our ility to ssess the effects of expected gin nd outcome proility on decisionmking ecuse there ws single correct choice identi ed in ech tril, mking it dif cult to correlte ny spect of the choices mde y our niml sujects with neuronl ctivity. In experiment 2, we therefore omitted the centrlly locted colour tht identi ed only one of the responses s reinforced nd insted llowed sujects to choose either of the two responses while we systemticlly vried the gin tht could e expected from ech response cross 5±7 locks of trils (men; 5:8). The ctul choices mde y sujects were then used s n estimte of the vlution of ech response y the niml on ech tril nd neuronl dt ws relted directly to this ehviourl redout of the niml's decision process. Figure 3 shows, for ly identicl trils in which the niml chose to shift gze into the response eld of the neuron under study, the modultion in ctivity of n intrprietl neuron in this freechoice tsk. The neuron ws more ctive during lock of trils rewrded with.15 ml of juice (Fig. 3, thick lck line) thn in Trget onset 5 1, 1,5 ms 4 2 * * * * * * fixtion fixtion n = Expected gin rtio CH9834 CH9834 Figure 3 Modultion of the ctivity of single intrprietl neuron y expected gin in free-choice tsk. The volume of juice delivered for ech response ws vried cross locks of sccdic choice trils., Firing rte of n intrprietl neuron on trils in which sujects chose to shift gze into the response eld, s in Fig. 1. Thick lck line, expected gin rtio ˆ :75 (n ˆ 75); thick grey line, expected gin rtio ˆ :25 (n ˆ 11). Rster pnels plot spike times during the rst 1 trils in oth the high-gin (drk grey) nd low-gin (light grey) locks. Arrows plot, sequentilly, the men times of centrl xtion stimulus offset nd sccde onset in high- (lck rrows) nd low- (grey rrows) gin locks., Men ring rte (6 s.e.) during ech intervl plotted ginst expected gin, for movements into the response eld. nother lock of trils in which the sme movement ws rewrded with only.5 ml of juice (Fig. 3, thick grey line). In fct, during the high-gin lock the neuron ecme ctivted efore the onset of the two choice trgets, pttern of ctivtion tht cnnot e ttriuted to response to trget onset. We lso mesured the verge ring rte of this neuron during six 2-ms epochs (erly xtion, lte xtion, erly, lte, pre-movement nd post-movement). Figure 3 shows the ring rte of this neuron (men 6 s:e:) during these epochs (note tht two of these intervls, erly xtion nd lte xtion, re efore the illumintion of the trgets). Firing rte incresed with expected gin during the erly xtion (r ˆ :158, P, :25), lte xtion (r ˆ :181, P, :1), erly (r ˆ :263, P, :1) nd lte (r ˆ :187, P, :1) intervls, ut not round the time of the movement. These dt con rm the correltion etween neuronl ctivtion nd the gin tht could e expected from prticulr movement, s reported in the previous experiments. The gol of this experiment, however, ws to directly correlte neuronl ctivity with the niml's estimte of the vlue of the two possile movements. Figure 4 presents the choices the suject mde cross ll locks of trils during this recording session. Consistent with Herrnstein's mtching lw 14 for choice ehviour, there ws liner reltionship etween the proportion of trils on which the niml chose the trget inside the response eld nd the proportion of totl juice ville for gze shifts to tht trget (r ˆ :96, P, :8) 35,36. Across 36 dt sets, there ws high correltion etween the frequency with which monkeys shifted gze to trget nd the proportion of totl juice ville for gze shifts to tht trget (men r ˆ :89, men P ˆ :3, men slope ˆ 1:86, men intercept ˆ 2 :45). Thus, the choice ehviour of our sujects relily re ected the gin 236 NATURE VOL 4 15 JULY

5 Proportion of trils into RF Expected gin rtio 4 2 fixtion n = Estimted vlue fixtion CH9834 ssocited with ech movement. In susequent nlyses, we therefore used choice frequencies s n estimte of the suject's reltive vlution of the two reinforced responses. To nlyse the reltionship etween the tril-y-tril ctivity of this neuron nd the vlution of ech choice y the suject, on ech tril we computed ehviourl estimte of the sujective vlue of movement into the response eld, sed on Herrnstein's meliortion theory 23, y computing the difference in the rte of reinforcement the niml hd otined from ech of the two possile choices over the preceding 1 trils (estimted vlue). Figure 4 shows the men ring rte of the neuron s function of this estimted vlue, during ech mesured intervl, for ll trils on which the niml shifted gze into the response eld. The ring rte of this neuron incresed s the estimted vlue of movement into the response eld incresed during the erly xtion (r ˆ :24, P, :4), lte xtion (r ˆ :152, P, :31), erly (r ˆ :18, P, :1) nd pre-movement (r ˆ :144, P, :4) intervls. The ring rte of this neuron ws uncorrelted with sccde mplitude, velocity nd ltency during ll six mesured intervls, nd thus these motor vriles cnnot ccount for the reltionship etween ring rte nd the sujective vlue of movement into the response eld. We recorded the ctivity of 36 intrprietl neurons from two monkeys performing this free-choice tsk. Overll, the regression slopes for estimted vlue were signi cntly greter thn zero, t some point during trils, for 56% of the neurons in the prietl popultion, while the regression slopes for the chosen movement were signi cntly greter thn zero for 89% of the popultion (Tle 1). Figure 4c shows the men (6 s.e.) regression slope for the estimted vlue of movement into the response eld (circles) during ech epoch, s well s the men (6 s.e.) regression slope for the chosen movement (tringles). The estimted vlue of movement into the response eld signi cntly modulted ctivity in our intrprietl neuronl popultion during the erly xtion, lte c Regression slope n = 36 EF LF EV LV PR PO Figure 4 Correltion of ring rte with ehviourl estimte of the sujective vlue of the two movements., Proportion of trils on which the monkey chose the trget inside the neuronl response eld plotted ginst expected gin. Line indictes est- t liner regression., Men ring rte (6 s.e.) during ech intervl plotted ginst ehviourl estimte of the sujective vlue of ech response, computed on ech tril from the difference in the reinforcement rtes otined from the two possile movements during the preceding 1 trils 24. c, Men (6 s.e.) regression slope for estimted vlue ( lled circles) nd the chosen movement ( lled tringles) plotted ginst time (n ˆ 36 neurons). Intervls s in Fig. 1c, except: EF, erly xtion; LF, lte xtion. xtion nd erly epochs (single-smple t-tests, P, :5). The movement chosen y the niml signi cntly modulted ctivity in this sme popultion of neurons during the lte xtion, erly, lte nd pre-movement epochs. Thus, when n niml is presented with choice etween two possile sccdic gze shifts, the niml's estimte of the reltive vlue of these two movements is correlted with the ctivtion of intrprietl neurons. The ctivtion of intrprietl cortex therefore ppers to re ect the decision processes nimls use to guide ehviour. Discussion Our results indicte tht decision-theoretic model of the sensory± motor process my provide powerful lterntive pproch to trditionl sensory nd motor neurophysiologicl models of response selection. Experiment 1 indictes tht oth the gin expected from prticulr response nd the proility tht prticulr response will e required systemticlly increse the ctivtion of neurons in posterior prietl cortex. Furthermore, this in uence is seprle from the effects of the immedite environment nd from the neurl events tht govern movement dynmics. The effects of expected gin nd outcome proility were strongest efore the time t which the niml knew which of the two possile responses would e rewrded. Experiment 2 shows tht when n niml is free to choose etween lterntive responses, the gin expected from ech possile ction exerts correlted in uence on oth the choice ehviour of the niml nd the ctivtion of posterior prietl neurons. In our free-choice tsk, oth monkeys nd posterior prietl neurons ehved s if they hd knowledge of the gins ssocited with different ctions. These ndings support the hypothesis tht the vriles tht hve een identi ed y economists, psychologists nd ecologists s importnt in decision-mking re represented in the nervous system. Our dt re, however, dif cult to reconcile with trditionl sensory-ttentionl or motor-physiologicl models. For exmple, sensory-ttentionl models typiclly ttriute modultions in the ctivity of ly responsive neurons to chnges in the ehviourl relevnce of stimuli 26 nd, sed on these models, it could e rgued tht our mnipultions of expected gin nd outcome proly merely ltered the ctivity of intrprietl neurons. This interprettion seems unlikely for two resons. First, when n niml is instructed to pln gze shift to one of two simultneously presented eccentric stimuli, intrprietl neurons re insensitive to chnges in the ehviourl relevnce of either stimulus when it is not the trget of sccde 34. Second, in experiment 2 we showed tht intrprietl neuronl ctivity ws modulted y chnges in the estimted vlue of ech response during the xtion intervls efore the onset of the response trgets, when sujects were xting the centrl LED in otherwise totl drkness. We nd this pttern of ctivtion dif cult to ttriute to n ttentionl modultion of ly evoked ctivity. It might lso e suggested tht the modultions in neuronl ctivity we evoked y chnges in expected gin, outcome proility nd estimted vlue re ect chnges in the degree to which nimls pln prticulr movements. Choice ehviour, such s tht shown y sujects in experiment 2, might thus re ect the outcome of covert competition etween movement plns weighted y the estimted vlue of ech possile ction. However, ecuse such model must include n estimte of response vlue it is essentilly equivlent to decision-theoretic model. Although the decision vriles we hve exmined here systemticlly modulted the ctivity of intrprietl neurons in our tsks, these effects were, for most neurons, con ned to the erly portions of ech tril. in ech tril, intrprietl neurons were more strongly modulted y the niml's movement pln thn y expected gin, outcome proility or the niml's estimte of response vlue. This my indicte tht intrprietl cortex lies close to the motor output stges of the sensory±decision±motor process. NATURE VOL 4 15 JULY

6 These dt my lso indicte tht other rin res elieved to prticipte in decision-mking, such s prefrontl cortex 37, might represent decision vriles throughout the tril. In conclusion, our results indicte tht neuroiologicl frmework for the study of choice sed upon the sme clssicl decision theory tht hs guided ehviourl studies of the choices humns nd nimls mke my provide powerful prdigm for studying the sensory±decision±motor process. Moreover, this frmework indictes tht mny of the modultory in uences ttriuted to sensory ttention or motor plnning might e more precisely descried s re ection of decision processes. The in uence of these vriles on the ctivity of posterior prietl cortex, rin re elieved to prticipte in the trnsformtion of sensory signls into motor commnds, indictes tht decision-theoretic frmework might e useful tool for understnding the neurophysiology of sensory-guided ehviour. M... Methods Single intrprietl neurons were studied in the rins of three rhesus monkeys trined to perform eye movements, in response to s, for fruit juice rewrd. Stndrd electrophysiologicl, ehviourl nd histologicl techniques were employed, s descried 34. All procedures were pproved y the New York University Animl Cre nd Use Committee nd were in complince with the Pulic Helth Service's Guide for the Cre nd Use of Animls. Ech experiment egn with the electrophysiologicl isoltion of single intrprietl neuron. Animls were then instructed to mke series of 5±2 eye movements from centrl strting position to successively illuminted LEDs rndomly selected from mong severl hundred LEDs locted t different peripherl positions. We used these movements to identify n eccentric LED tht elicited movement for which the neuron ws mximlly ctive ( movement into the response eld) nd n eccentric LED tht elicited movement for which the neuron ws minimlly ctive ( movement out of the response eld). Experiment 1. For experiment 1, this mpping procedure ws followed y series of d sccde trils in totl drkness. Ech of these trils egn with the illumintion of yellow LED locted directly in front of the niml. A rndom intervl (2±5 ms) fter the suject hd ligned his gze (62 8) with this LED, the two eccentric yellow response LEDs identi ed y our mpping procedure were illuminted. After nother rndom intervl (2±8 ms), the centrl LED chnged colour to either red or green, instructing the suject tht sccde ligning gze with either the upper or lower eccentric LED, respectively, would e rewrded with drop of juice. After nl rndom intervl (2± 8 ms), the centrl LED ws extinguished nd the monkey ws rewrded if he shifted gze into lignment with (64 8) the correct eccentric LED. We then determined whether the ctivtion of intrprietl neurons ws modulted y systemtic chnges in the gin expected from ech possile movement or the proility tht ech of the two possile movements would e instructed. Animls typiclly performed this tsk correctly on out 9% of trils. Expected gin. While ech of 4 neurons ws studied we vried, in 3±7 sequentil locks of out 1 trils ech, the mount of juice rewrd the nimls received oth for movements into nd movements out of the response eld (expected gin). Across locks, the sum of the juice ville from these two possile movements ws held constnt, nd the proility tht either response would e instructed on given tril (outcome proility) ws held constnt t.5. An experiment typiclly egn with lock in which ech movement ws reinforced eqully, nd then pirs of locks of complementry high gin/low gin conditions were rndomly interleved. Outcome proility. While ech of 2 neurons ws studied we vried, in 5±7 sequentil locks of out 1 trils ech, the proility tht ech of the two responses would e instructed while the gin expected from ech movement ws held constnt. A lock in which ech movement ws instructed eqully often ws typiclly run rst, nd then pirs of locks with complementry high proility/low proility conditions were rndomly interleved. Experiment 2. Thirty-six neurons were studied in two rhesus monkeys performing sccdic choice trils, which were similr to d sccde trils ut hd no centrlly locted colour. Ech of these trils egn with the illumintion of yellow LED locted directly in front of the niml. 5 ms fter the suject hd ligned his gze (62 8) with this LED, the two eccentric yellow response LEDs identi ed y our mpping procedure were illuminted. After rndom intervl (5±8 ms), the centrl LED ws extinguished nd the monkey ws rewrded if he shifted gze into lignment with (64 8) either eccentric LED. The gin tht could e expected from ech movement ws vried systemticlly cross 5±7 locks of out 1 trils ech. A lock in which ech movement ws reinforced eqully ws typiclly run rst, nd then pirs of locks of complementry high gin/low gin conditions were rndomly interleved. Received 3 April; ccepted 25 My Descrtes, R. Tretise on Mn (trns. Hll, T. S.) (Hrvrd Univ. Press, Cmridge, Msschusetts, 1662:1972). 2. Sherrington, C. The Integrtive Action of the Nervous System (Yle Univ. Press, New Hven, 196). 3. Pvlov, I. P. Conditioned Re exes: An Investigtion of the Physiologicl Activity of the Cererl Cortex (trns. Anrep, G. V.) (Oxford Univ. Press, Oxford, 1927). 4. Pen eld, W. The Mystery of the Mind: A Criticl Study of Consciousness nd the Humn Brin (Princeton Univ. Press, Princeton, 1975). 5. Asnum, H. & Skt, H. Functionl orgniztion of corticl efferent system exmined with focl depth stimultion in cts. J. Neurophysiol. 3, 35±54 (1967). 6. Glimcher, P. W. & Sprks, D. L. Movementselection indvnceof ction. Nture 355, 542±545 (1992). 7. Schll, J. D. & Hnes, D. P. Neurl sis of sccde trget selection in the frontl eye eld during serch. Nture 366, 467±469 (1993). 8. Bsso, M. A. & Wurtz, R. H. Modultion of neuronl ctivity y trget uncertinty. Nture 389, 66±69 (1997). 9. Dorris, M. C. & Munoz, D. P. Sccdic proility in uences motor preprtion signls nd time to sccdic initition. J. Neurosci. 18, 715±726 (1998). 1. von Holst, E. The Behviorl Physiology of Animls nd Mn. Selected Ppers of Eric von Holst (Univ. of Mimi Press, Corl Gles, Florid, 1973). 11. Bernstein, N. in Humn Motor Actions: Bernstein Ressessed (ed. Whiting, H. T. A.) 77±119 (Elsevier, New York, 1984). 12. Weiss, P. Self-differentition of the sic ptterns of coordintion. Comp. Psych. Monogrphs 17, vol. 4, 1±96 (1941). 13. Gllistel, CR. Forging for rin stimultion: towrd neuroiology of computtion. Cognition 5, 151±17 (1994). 14. Herrnstein, R. J. Reltive nd solute strength of response s function of frequency of reinforcement. J. Exp. Anl. Behv. 4, 267±272 (1961). 15. DeVilliers, P. A. & Herrnstein, R. J. Towrd lw of response strength. Psych. Bull. 83, 1131±1153 (1976). 16. Stddon, J. E. R. & Motherl, S. On mtching nd mximizing in opernt choice. Psych. Rev. 85, 436± 444 (1978). 17. Pyke, G. H., Pullim, H. R. & Chrnov, E. L. Optiml forging: selective review of theory nd tests. Q. Rev. Biol. 52, 137±154 (1979). 18. Stephens, D. W. & Kres, J. R. Forging Theory (Princeton Univ. Press, Princeton, 1986). 19. von Neumnn, J. & Morgenstern, O. The Theory of Gmes nd Economic Behvior (Princeton Univ. Press, Princeton, 1944). 2. Arnuld, A. & Nichole, P. The Art of Thinking: Port-Royl Logic (trnsl. Dickoff, J. & Jmes, P.) (Bos- Merrill, Indinpolis, 1562:1982). 21. Bernoulli, D. The Works (Birkhuser, Boston, 1738:1982 trnsl. D. Speiser). 22. Khnemn, D., Slovic, P. & Tversky, A. Judgement Under Uncertinty (Cmridge Univ. Press, New York, 1982). 23. Herrnstein, R. J. & Vughn, W. Jr in Limits to Action: The Alloction of Individul Behvior (ed. Stddon, J. E. R.) 143±176 (Acdemic, New York, 198). 24. Schoener, T. W. Theory of feeding strtegies. Ann. Rev. Ecol. Syst. 2, 369±44 (1971). 25. Kres, J. R., Kcelnik, A. & Tylor, P. Test of optiml smpling y forging gret tits. Nture 275, 27±31 (1978). 26. Golderg, M. E., Coly, C. L. & Duhmel, J.-R. Representtionof visuomotorspcein the prietl loe of the monkey. Cold Spring Hr. Symp. Qunt. Biol. 55, 729±739 (199). 27. Gottlie, J. P., Kusunoki, M. & Golderg, M. E. The representtion of slience in monkey prietl cortex. Nture 391, 481±484 (1998). 28. Shdlen, M. N. & Newsome, W. T. Motion perception: Seeing nd deciding. Proc. Ntl Acd. Sci. USA 93, 628±633 (1997). 29. Gndt, J. & Anderson, R. A. Memory relted motor plnning ctivity in posterior prietl cortex of monkey. Exp. Brin Res. 7, 216±22 (1988). 3. Snyder, L. H., Bttist, A. P. & Andersen, R. A. Coding of intention in the posterior prietl cortex. Nture 386, 167±17 (1997). 31. Brcewell, R. M., Mzzoni, P., Brsh, S. & Andersen, R. A. Motor intention ctivity in the mcque's lterl intrprietl re. II. Chnges of motor pln. J. Neurophysiol. 76, 1457±1464 (1996). 32. Pltt, M. L. & Glimcher, P. W. Representtion of prior proility nd movement metrics y re LIP neurons. Soc. Neurosci. Astr. 23, 16 (1997). 33. Pltt, M. L. & Glimcher, P. W. Neurons in re LIP crry informtion correlted with movement proility nd rewrd mgnitude. Invest. Ophthlmol. Vis. Sci. 39, 326 (1998). 34. Pltt, M. L. & Glimcher, P. W. Responses of intrprietl neurons to sccdic trgets nd distrctors. J. Neurophysiol. 78, 1574±1589 (1997). 35. Ctni, A. C. Concurrent performnces: seline for the study of reinforcement mgnitude. J. Exp. Anl. Behv. 6, 299±3 (1963). 36. Dvenport, J. W., Goodrich, K. P. & Hgguist, W. W. Effects of mgnitude of reinforcement in Mcc specios. Psych. Sci. 4, 187±188 (1966). 37. Bechr, A., Dmsio, H., Trnel, D. & Anderson, S. Dissocition of working memory from decision mking within humn prefrontl cortex. J. Neurosci. 18, 428±437 (1998). Acknowledgements. We thnk J. Mones nd S. Corthers for technicl ssistnce; W. T. Newsome, E. M. Brnnon, M. Gzznig, A. Hndel nd J. A. Movshon for comments on the mnuscript nd experiments; nd M. N. Shdlen nd W. T. Newsome for dvice on nlysis. This projectws fundedy thenei (M.L.P.) nd the McKnight Foundtion (P.W.G.). Correspondence nd requests for mterils should e ddressed to M.L.P. (e-mil: mpltt@cns.nyu.edu). 238 NATURE VOL 4 15 JULY