Sensory-motor mechanisms in human parietal cortex underlie arbitrary visual decisions

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1 Sensory-motor mechnisms in humn prietl cortex unerlie ritrry visul ecisions 28 Nture Pulishing Group Annlis Tosoni 1,2, Gspre Glti 2 4, Gin Luc Romni 1,2 & Murizio Corett 1,2,5 The neurl mechnism unerlying simple perceptul ecision-mking in monkeys hs een recently conceptulize s n integrtive process in which sensory evience supporting ifferent response options ccumultes grully over time. For exmple, intrprietl neurons ccumulte motion informtion in fvor of specific oculomotor choice over time. It is uncler, however, whether this mechnism generlizes to more complex ecisions tht re se on ritrry stimulus-response ssocitions. In tsk requiring ritrry ssocition of visul stimuli (fces or plces) with ifferent ctions (eye or hn-pointing movements), we foun tht ctivity of effector-specific regions in humn posterior prietl cortex reflecte the strength of the sensory evience in fvor of the preferre response. These regions i not respon to sensory stimuli per se ut integrte sensory evience towr the ecision outcome. We conclue tht even ritrry ecisions cn e meite y sensory-motor mechnisms tht re completely triggere y contextul stimulus-response ssocitions. Humn ecision-mking is thought to involve higher-orer tskinepenent cognitive processes, which re istinct from tsk-specific perceptul mechnisms tht provie evience in fvor of prticulr choice n from motor mechnisms tht re responsile for proucing the chosen ction 1,2. However, t lest simple visul ecisions in monkeys re meite y neurl mechnisms tht re emee in the sensory-motor pprtus. In criticl experiments with monkeys trine to iscriminte the irection of moving ots, oculomotor neurons in the lterl intrprietl re (LIP) increse their response in proportion to the level of sensory evience in fvor of sccic choice towr their receptive fiel 3,4. It is currently unknown, however, whether the propose mechnism lso generlizes to humn ecisions, which re inste chrcterize y ritrry stimulus-response ssocitions tht chnge over time ccoring to contextul fctors. To unerstn how sensory representtions re converte into the ehviorl outcome of ritrry ecisions, we trine humn sujects to ssocite ifferent visul stimuli (fces or plces) with ifferent ctions (sccic eye or hn-pointing movements). We systemticlly mnipulte the level of noise tht ws e to the visul stimuli to stuy ecision-mking s function of the quntity of sensory evience ville n to evlute, especilly for stimuli ner the psychophysicl threshol (tht is, t 5% ccurcy), ecisions etween competing response options in the sence of vli sensory evience. If ritrry humn visul ecisions re me on the sis of mechnisms tht re nlogous to those ientifie in monkey stuies 3,4, then ctivity in corticl regions responsile for the selection of the pproprite response shoul reflect the level of certinty of the ecision. We stuie specific set of regions in humn prietl n frontl cortex tht crry motor signls tht re specific for plnning or executing either hn-pointing or sccic eye movements, n we ske whether preprtory ctivity in these regions represente the level of sensory evience in fvor or ginst the motor choice for which they re selective. Criticlly, sensory evience in our proceure ws provie y visul stimuli (fces or plces) tht normlly o not sensorilly rive these regions ut h een ritrrily ssocite with specific response in the context of the ecision tsk. We foun tht two pointing-selective regions in meil prietl cortex, which o not respon to fce or plce stimuli per se, showe pttern of ctivity tht scle with the strength of the sensory evience in fvor of pointing response. A posterior intr-prietl region tht ws selective for scces showe more complex pttern, with mixture of ecision n ttention signls relte to perceptul ifficulty. RESULTS We recore loo oxygen level epenent (BOLD) signl time series with functionl mgnetic resonnce imging (fmri) uring visul ecision tsk using n event-relte fmri esign. In typicl tril (Fig. 1), either fce or plce imge ws centrlly presente with peripherl visul trget. Following ely, sujects reporte whether they h seen fce or plce y performing scce or pointing movement, respectively, towr the rememere loction of the visul trget. We e vrile mount of noise to the fce/plce imge on ech tril to mnipulte the mount of sensory evience in fvor of sccic/pointing ecision. To mtch the level of sensory evience cross sujects, ech suject performe ehviorl session in which 1 Deprtment of Clinicl Sciences n Bioimging n 2 ITAB, Institute for Avnce Biomeicl Technologies, G. Annunzio Fountion, Vi ei Vestini 31, Chieti 6613, Itly. 3 Deprtment of Psychology, Spienz University, Vi ei Mrsi 78, Rom 185, Itly. 4 Neuroimging Lortory, Snt Luci Fountion, Vi Aretin 36, Rom 179, Itly. 5 Deprtments of Neurology, Riology, Antomy & Neuroiology, Wshington University School of Meicine, 4525 Scott Avenue, St. Louis, Missouri 6311, USA. Corresponence shoul e resse to A.T. (tosoni@npg.wustl.eu). Receive 19 August; ccepte 2 Octoer; pulishe online 9 Novemer 28; oi:1.138/nn.2221 NATURE NEUROSCIENCE ADVANCE ONLINE PUBLICATION 1

2 Time Dely 3 ms 1.5 s 8 ms Inter-tril intervl Plce responses s 1% 75% 5% 25% % % 5% 1% 5% % Unmske fces Amount of noise Unmske plces % 25% 5% 75% 1% Evience for plce Figure 1 Decision tsk. () Proceure. A centrl imge ws presente to the sujects ( photogrph of fce or plce with vrile mount of white noise superimpose) together with peripherl trget ( circle). After ely, the fixtion point chnge color (go signl) n prticipnts either move their eyes (for fces) or pointe with their right inex finger (for plces) to the memorize trget loction n then immeitely returne to the strting point. () Psychophysics n exmple of iniviul selection of evience levels. The soli curve represents the est-fitting psychometric function for representtive suject, escriing the proility of giving plce response s function of the evience level in the imge. The sctter plot shows the rw t from which the estimte ws compute. Bottom, exmples of the five noise levels selecte for this suject y interpoltion of the psychometric function to yiel %, 25%, 5%, 75% n 1% evience for pointing response. 28 Nture Pulishing Group imges were ctegorize s either fces or plces. For ech suject, responses were fitte to psychometric function 5,6,whichwsthen interpolte so s to select stimuli ctegorize s plces %, 25%, 5%, 75% n 1% of the time (Fig. 1). Action-selective n preprtory signls Becuse we preicte tht sensory evience in fvor of given choice ws represente in corticl regions tht re responsile for the selection of the corresponing response, we conucte the min nlysis on specific set of pointing- n scce-selective regions of interest (ROIs) in prietl n frontl cortex (Fig. 2). These regions were iniviully loclize in ech suject y recoring seprte set of fmri scns uring locks of memory-guie pointing or sccic eye movements to visul trgets. We ientifie two pointing-selective ROIs in the precuneus, on the meil surfce of the prietl loe, which we lele the nterior prietl rech region (PRR; Fig. 3) n the posterior prietl rech region (pprr; Fig. 4) for their reltive loctions on the sis of the loclizer scns. On the lterl surfce of the prietl loe, we ientifie scce-selective ROI in the meil nk of the posterior intrprietl sulcus (pips; Fig. 5). In frontl cortex, we ientifie three ction-selective ROIs (Fig. 6). Two were pointing-selective: left centrl sulcus region spnning sensorymotor cortex (SMC) n region in the orsl spect of the precentrl sulcus or frontl rech region (FRR, SMC; Fig. 6). The thir one ws scce-selective n ws locte t the intersection of the precentrl sulcus with the posterior en of the superior frontl sulcus (frontl eye fiels, FEF; Fig. 6). Becuse of their loction n results from previous functionl imging stuies, pointing-selective regions in posterior prietl cortex my e homologs of mcque res meil intrprietl re n V6A, which re prt of the monkey PRR 7 1, n scce-selective regions pips n FEF my e homologs of mcque res LIP n FEF, respectively For ech ROI, we verge the BOLD signl time series for ech conition of the ecision tsk cross trils in ech iniviul n then verge the time series cross sujects (see Methos). Inspection of the time series showe first pek corresponing to the presenttion of the visul stimulus (fce, plce) n the ssocite ecision, n secon pek corresponing to the execute movement. First, we etermine whether ctivity uring the first pek ws significntly moulte y the plnne response. Uner conitions in which movement selection ws esier (tht is, when the plce/fce stimulus ws clerly visile, 1% level of evience), oth PRR n pprr respone more strongly when sujects plnne pointing movement thn n eye movement (response effector (pointing, scce) y time (time points 1 6) interction; PRR: F 5,55 ¼ 8.35, P o.1; pprr: F 5,45 ¼ 4.37, P ¼.2; Figs. 3 n 4). Scce-selective signls in the pips were weker n emerge towr the en of the ely perio (response effector min effect: F 1,9 ¼ 3.59, P ¼.9; post hoc time point 5, P ¼.1; time point 6, FEF FRR SMC pips PRR pprr x = 11 y = 65 z = +54 Scce selective Pointing selective Pointing selective Figure 2 Pointing- n scce-selective regions in posterior prietl n frontl cortex. Conjunction of iniviul ROIs from loclizer scn for FEF, FRR, SMC, pips, PRR n pprr shown on orsl (on the left) n orso-meil (on the right) view of the inflte surfce of the left hemisphere of the PALS tls 42 n coronl, sgittl n trnsversl slices of the Colin rin ADVANCE ONLINE PUBLICATION NATURE NEUROSCIENCE

3 28 Nture Pulishing Group Sujects Decision Decision Pssive Pssive PRR 16, 5, , 6, +51 Plces Fces e Pointing contr 5% Pointing 5% Scce Pointing ipsi P ¼.4; Fig. 5). Roust effector-selective intentionl signls in posterior prietl cortex contrste with reltively wek effectorselective preprtory ctivity in frontl regions. The SMC region showe only wek pointing selectivity uring the ely, wheres we oserve no selectivity for pointing in the frontl FRR region (Fig. 6c) or for scces in FEF (Fig. 6). However, ll of these regions showe roust effector selectivity uring the response phse of the tril. Accumultion of sensory evience in prietl cortex We next consiere whether the level of ctivity covrie with the level of sensory evience. Inspection of the BOLD signl time series on trils in which sujects selecte pointing response showe tht the mgnitue of the first pek vrie with the strength of the sensory evience in oth PRR n pprr (1% 4 75% 4 5% evience; evience y time interction; PRR: F 1,11 ¼ 2.71, P ¼.5; pprr: F 1,9 ¼ 3.4, P ¼.2; Figs. 3c n 4c). In the pips region, moultion y the sensory evience emerge reltively lte in the course of the ely, similr to wht we oserve for scce selectivity (evience y time interction: F 12,18 ¼ 2.8, P ¼.24; Fig. 5c). Notly, this moultion pprr ws not evient uring the secon pek for the movement execution in ny of the three regions. This is consistent with the ie tht ecisions were me erly on fter Sujects stimulus presenttion n tht the qulity of 1 6 sensory informtion oes not ffect the execution of movement once threshol for ecision is reche. 7, 75, +45 Bolstering the notion of n ccumultor.4 Decision mechnism tht integrtes sensory evience into premotor pln, we looke for the presence of moultion y negtive sensory evience (tht is, fvoring the nonpreferre response). At lest in PRR (Fig. 3f)npPRR (Fig. 4f), the wekest pek response ws Pssive Plces Pssive c f % Plce pointing 75% Plce pointing 5% Pointing 1% Fce scce 5% Scce Figure 3 PRR. () Left n right ntomicl loction of PRR. Color scle inictes overlp of iniviul ROIs selecte on the sis of the loclizer scns isplye on the inflte surfce of the PALS tls 42.() BOLD signl time series for pointing or sccic eye movements to contrlterl or ipsilterl trgets. (c) Time series for trils in which sujects selecte pointing movement to plce stimuli with ifferent levels of positive sensory evience (1%, 75% or 5%). () Percent signl chnge to fce n plce stimuli uring pssive stimultion efore trining on the ecision tsk (pssive) n uring the ecision tsk (ecision). Error rs represent the s.e.m. (e) Time series for trils in which stimuli provie no useful informtion (5% evience) n sujects selecte either pointing or eye movements. (f) Time series for trils in which sujects selecte n eye movement to fce stimuli t ifferent levels of sensory evience (1%, 75% or 5%). oserve when 1% fce stimuli, strongly linke to sccic eye movement, were presente. This qulittive oservtion ws vlite y n ANOVA compring the level of sensory evience for the preferre effector over time points. For exmple, in pointing-selective regions, we compre responses to 1% plce, 75% plce (25% fce), 25% plce (75% fce) n % plce (1% fce) stimuli. We oserve significnt interction of level of sensory evience y time (PRR: F 15,165 ¼ 3.51, P ¼.1; pprr: F 15,135 ¼ 1.95, P ¼.23), which ws significnt t the pek of the response (time point 4) (post hoc t tests, PRR: 1% plce 4 75% plce, P o.1; 4 25% plce, P o.1; 4 % plce, P o.1; pprr: 1% plce 4 75% plce, P ¼.11; 4 25% plce, P ¼.42; 4 % plce, P o.1). In the sccic region pips (Fig. 5f), we lso foun n interction of level of sensory evience y time (F 15,135 ¼ 1.88, P ¼.3), which ws significnt t the en of the ely (time point 6), similr to wht we foun for scce selectivity n positive sensory evience (post hoc t tests, 1% fce 4 25% fce, P ¼.4; 4 % fce, P o.1). These results inicte tht ll of the effector-specific regions in posterior prietl cortex re moulte y oth positive n negtive sensory evience. Overll, these finings strongly suggest tht ritrry ecisions rely on n ccumultor mechnism tht integrtes sensory evience towr motor response. To rule out the possiility tht this moultion y sensory evience reflecte low-level perceptul effect, such s stronger response to clerly visile stimuli (1% fce or plce) thn to noisy ones (5% fce/plce), or ifferentil specificity of pointing or scce regions to these stimulus ctegories, we compre sensory responses to fce n plce stimuli efore n fter sujects were expose to the ecision tsk. We rn locks of trils involving the pssive presenttion of fce n plce stimuli efore the sujects were ever expose to the visul ecision tsk. Before trining, the pssive sensory responses to plce or fce imges were generlly wek in posterior prietl cortex. However, uring the ecision tsk (tht is, fter trining), responses ecme strong n selective. This ifference, t lest in PRR, cnnot e Pointing contr Pointing ipsi c +13, 75, +45 Decision Fces e Figure 4 pprr. f. Dt is presente s in Figure 3. 5% Pointing 5% Scce.1 f % Plce pointing 75% Plce pointing 5% Pointing 1% Fce scce 5% Scce NATURE NEUROSCIENCE ADVANCE ONLINE PUBLICATION 3

4 28 Nture Pulishing Group pips c Sujects , 63, , 6, Decision Decision Pssive Pssive Plces Fces ccounte for y vrition in rousl or ttention, s the ctivtion ecme not only stronger ut lso more selective, for the stimulus ctegory ssocite with the preferre response (experiment (pssive, ecision) y stimulus (fce, plce) interction: F 1,1 ¼ 8.13, P ¼.17; Fig. 3). In pprr, we oserve the sme tren, lthough it ws not significnt (F 1,8 ¼.96, P ¼.35; Fig. 4), wheres the response to oth types of stimuli increse uring the ecision tsk in the pips region (Fig. 5). In summry, the response in these regions is not the result of low-level sensory fctors ut is proly the prouct of lerning the ritrry visuo-motor ssocition. Sptil n ecision signls in prietl cortex Activity in posterior prietl cortex ws not only moulte y the strength of the sensory evience ut lso y the irection of movement or sptil loction of the trget. In fct, the pointing PRR (Fig. 2), pointing pprr (Fig. 3) n sccic pips regions (Fig. 4) showe stronger responses for trgets/movements towr the contrlterl visul spce (visul fiel y time interction, PRR: F 5,55 ¼ 5.69, P o.1; pips: F 5,45 ¼ 5.21, P o.1; visul fiel min effect, pprr: F 1,9 ¼ 12.17, P ¼.6). This sptil selectivity ws inepenent of motor plnning signls, s inicte y the lck of significnt interction of response effector y visul fiel (response effector y visul fiel y time, PRR: F 5,55 ¼.11, P ¼.987; pprr: F 5,45 ¼ 1.64, P ¼.167; pips: F 5,45 ¼.32, P ¼.894). We lso nlyze the response in PRR, pprr n pips regions when the stimuli provie no useful informtion (5% evience) s function of whether sujects selecte pointing or eye movements. This is n importnt test of whether these regions ctully coe for the motor ecision inepenently of the qulity of sensory informtion. Notly, lthough PRR ws not moulte y motor choice (Fig. 3e), preprtory signls in oth pprr (Fig. 4e) n pips regions (Fig. 5e) preicte the suject s ecision. In e Pointing contr Pointing ipsi 5% Pointing 5% Scce Figure 5 pips region. f. Dt is presente s in Figure 3. c e f FRR 28, 6, +54 Pointing contr Pointing ipsi pprr, the erly prt of the time course 1% Fce scce (incluing the pek) i not istinguish etween pointing n eye movements, consistent with n ongoing competition etween the 5% Scce two response outcomes; however, ifferentition emerge lter in the course of the ely (time point 5), which is consistent with reltive ely in reching the ecision when the sensory evience ws poor (response effector y time interction, pprr: F 5,45 ¼ 2.73, P 1% Plce pointing 75% Plce pointing 5% Pointing ¼.31; post hoc t tests on time point 5, P ¼.1). In the pips region, the ecision to mke scce moulte ctivity fter the pek towr the en of the ely perio (response effector min effect: F 1,9 ¼ 6.35, P ¼.3), consistent with the lte emergence of other selective signls uring the ely. In summry, lthough ll regions were sensitive to the effector, the qulity of sensory informtion n the sptil loction of the trget, pprr n pips were lso moulte y the ctul choice to move. Sensory evience n ecision in frontl cortex In contrst with the prietl regions, the FRR (Fig. 6e) n the FEF scce-selective region (Fig. 6f) were not moulte y the level of sensory evience uring the ecision ely (evience y time interction, FRR: F 1,11 ¼.75, P ¼.667; FEF: F 1,8 ¼.59, P ¼.812). Even though these regions were clssifie s pointing- n scceselective on the sis of the loclizer scns n mnifeste effectorspecific ctivity uring execution (Fig. 6c,), they i not show strong selective plnning ctivity n i not preict the outcome of the ecision when the stimuli were miguous. Sujects SMC 1% Plce pointing 75% Plce pointing 5% Pointing.1 Sujects f FEF 34, 3, , 3, +57 Pointing contr Pointing ipsi 1% Fce scce 5% Scce Figure 6 FRR, SMC n FEF. (,) Left hemisphere ntomicl loction of FRR, SMC (pointing) n FEF (scce) regions. (c,) BOLD signl time series for pointing or eye movements to contrlterl or ipsilterl trgets. (e) Time series for trils in which sujects selecte pointing movement to plce stimuli t ifferent levels of sensory evience (1%, 75% or 5%). (f) Time series for trils in which sujects selecte n eye movement to fce stimuli t ifferent levels of sensory evience (1%, 75% or 5%). 4 ADVANCE ONLINE PUBLICATION NATURE NEUROSCIENCE

5 28 Nture Pulishing Group c z = +66 z = +6 z = +54 z = +48 z = +42 PRR SMC 1% Plce pointing 75% Plce pointing.3 5% Pointing These negtive results uring the ely, vis-à-vis the selectivity of responses uring execution n the pttern in posterior prietl cortex, suggest tht the premotor regions FRR n FEF were more involve in lte motor selection n/or execution thn in the trnsformtion of sensory informtion into motor plns. In SMC, however, there ws some evience for ccumultion of sensory evience n specificity for rm motor plnning (Fig. 6c,e). The response uring the ecision ely ws stronger for 1% thn for 75% or 5% plce stimuli (sensory evience min effect, F 2,22 ¼ 7.17, P ¼.3). There ws lso stronger ely ctivity for pointing thn for scces (response effector min effect, F 1,11 ¼ 8.22, P ¼.15). Sensory evience outsie ction-selective regions Although our results strongly suggest tht posterior prietl cortex is preominntly influence y the ccumultion of sensory evience n ensuing motor ecisions, two importnt questions remin unnswere y the min ROI nlysis. First, re there other effector-specific regions tht lso show ecision signls? Secon, re there ny rin regions tht ccumulte sensory evience inepenently of motor pln or response type? In other wors, is there evience for neurl correlte of generl ecision-mking moule? Two recent fmri stuies report tht ctivity in left superior orso-lterl prefrontl cortex is comptile with such mechnism 15,16. We investigte these two questions y running voxel-wise ANOVA on the whole rin, with response effector, sensory evience n time s fctors. An interction of response effector y sensory evience y time woul ientify voxels in the rin tht re sensitive to oth response selection n sensory evience. Conversely, significnt interction of sensory evience y time woul e inictive of voxels tht re moulte y sensory evience inepenently of the specific motor response n my thus represent more generl ecisionmking mechnism PRR % Fce scce 5% Scce Figure 7 Whole rin nlysis: sensory evience n effector selectivity. () Color scle inictes overlp of iniviul PRR ROIs on the sis of loclizer scn mppe onto trnsverse slices of the Colin rin 43. () Multiple-comprison correcte z mp of the interction of response effector y sensory evience y time. (c) BOLD signl time series from PRR region in for trils in which sujects selecte either pointing or n eye movement to stimuli t ifferent levels of sensory evience. z score Sujects Consistent with the ROI nlysis, we foun n interction of response effector y sensory evience y time in meil prietl region in the precuneus tht completely overlppe with PRR (Fig. 7,). This re respone more strongly to pointing thn to sccic movements uring the ecision ely n showe moultion y sensory evience in the expecte irection (1% 4 75% 4 5% evience; Fig. 7c). The only other significnt region ws loclize in the left centrl sulcus n it ws lso entirely inclue in the SMC region (multiple comprison correcte z mp significnt t the cluster level of P ¼.5). These nlyses strongly n inepenently confirm the specificity of posterior prietl cortex n SMC in the ccumultion of sensory-motor evience. Next, we consiere whether ny region in the rin revele n effect of sensory evience irrespective of response effector. Severl nterior regions, incluing ventrl (left: 35, +43, +1; right: +43, +26, +24) n lterl prefrontl cortex (left: 36, 5, +25; right: +36,, +36), ilterl insul (left: 3, +18, +6; right: +36, +15, +2), presupplementry motor re (pre-sma, +14, +43), n nterior cingulte ( 4, +46, +1), showe significnt min effect of sensory evience (Fig. 8 c). Time series inspection revele stronger ctivtion for more ifficult stimuli (5% n 75% evience) thn for esier stimuli (1% evience). Notly, this effect ws inepenent of the response effector (scce or pointing). This pttern of results is consistent with role for these prefrontl regions in perceptul nlysis or lloction of ttention resources ut not in ccumultion of sensory evience or ecision-mking. We lso oserve min effect of sensory evience ilterlly in the IPS (left: 29, 63, +47; right: +3, 61, +46), which overlppe with the sccic region pips n similrly isplye sccic-selective motor ctivity (Fig. 8). Therefore, this prt of posterior prietl cortex contins mixture of perceptul-ttention, sensory evience n motor-ecision signls. Finlly, severl other rin regions showe ectivtion tht ws inepenent of stimuli n responses. The ectivtion increse with stimulus ifficulty: tht is, stronger for 5% n 75% thn for 1% evience. These regions inclue posterior cingulte, ventro-meil prefrontl cortex n ngulr gyrus, the min noes of the so-clle efult system 17,18, functionl network tht is consistently ectivte uring gol-irecte ehvior when compre with rest (see c Right insul (+36, +15, +2) Right VPFC (+43, +26, +24) % Plce pointing 1% Fce scce 75% Plce pointing 3 5 5% Pointing z score 5% Scce PreSMA (, +14, +43) Left pips ( 29, 63, +47) Figure 8 Whole rin nlysis: sensory evience. ( ) Multiple-comprison correcte z mp of the min effect of sensory evience is superimpose on selecte trnsverse slices of the Colin rin 43. BOLD signl time series for pointing n eye movements s function of sensory evience. presma, pre-supplementry motor re; VPFC, ventro-meil prefrontl cortex. NATURE NEUROSCIENCE ADVANCE ONLINE PUBLICATION 5

6 28 Nture Pulishing Group Supplementry Fig. 1 online for the loction n time series of these regions in reltion to the topogrphy of the efult network). The negtive moultion of these regions s function of tsk ifficulty is comptile with previously reporte lo- or ttention-epenent moultions of the efult network 19,2 ut not with role of these regions in the ccumultion of sensory evience. Notly, the region in orso-lterl prefrontl cortex tht hs een propose to e generl ecision-mking moule 16 flls in the orers of the efult network n, not surprisingly, showe signl ectivtion (see Supplementry Fig. 1). In conclusion, we foun no prefrontl region with positive moultion relte to sensory evience inepenent of the motor response. DISCUSSION Sensory evience n ecision signls in prietl cortex The min fining of our stuy ws tht ritrry visul ecisions involving the ssocition of stimulus to response i not involve generl ecision-mking moule ut rther epene on specific sensory-motor mechnisms tht ccumulte sensory informtion n pln motor ctions. Severl regions in humn posterior prietl cortex tht re specific for plnning n executing either pointing or sccic eye movements respone more strongly to stimuli tht provie more sensory evience towr motor ecision n tht were linke to the preferre response in the context of the ecision tsk. The moultion y sensory evience cnnot e expline y ifference in the sensory response to highly visile (1% evience) versus noisy stimuli (5% evience) ecuse these regions i not respon to highly visile plce or fce stimuli efore they ecme relevnt s prt of the ecision proceure. Rther, prietl cortex ecme strongly responsive to the relevnt stimulus ctegory (fce or plce) in the context of the ecision tsk. Although higher rousl or ttention my prtly ccount for n increment in the sensory rive of these regions, the enhncement ws specific for the stimulus ctegory (plces) ssocite with the preferre movement (pointing), t lest in the region PRR. Higher responsiveness to tsk-relevnt stimuli is consistent with reports of neurons in prietl cortex flexily coing stimulus fetures instructing selective tsk set Aitionl support for the ie tht prietl cortex functions s n ccumultor of sensory informtion is the moultion y oth positive (tht is, relte to the preferre response) n negtive sensory evience (tht is, relte to the nonpreferre response) (for exmple, scce responses to fce stimuli in pointing region). In ll three prietl regions (PRR, pprr n pips), the response scle with evience for oth preferre n nonpreferre responses (for exmple, 1% plce, 75% plce, 25% plce (75% fce) n % plce (1% fce) in pointing-selective PRR n pprr). This control is importnt ecuse it rgues ginst premotor interprettion. A highly visile (high evience) relevnt stimulus les to quicker ecision n thus potentilly les to n erlier n stronger uil-up of premotor ctivity for the preferre movement. Conversely, noisy stimulus (low evience) les to elye ecision n possily to elye n weker motor uil up. A premotor interprettion, however, preicts no moultion y negtive evience linke to the nonpreferre response. In contrst, we foun tht prietl cortex ctivity scle s function of oth positive n negtive evience, which is more consistent with sensory mechnism tht weights the ville sensory informtion 3,4. Prietl cortex contins not only sensory evience signls ut lso motor signls relte to the ecision. This conclusion is se on three oservtions. First, these prietl regions were selecte on the sis of their specificity for motor effectors in loclizer tsk tht comine plnning n execution, n, uring the ecision tsk, ll three of the regions showe effector-specific plnning ctivity. A functionl suivision of posterior prietl cortex in ction-specific regions (eye, fce n rm) is consistent in humns n monkeys. The loction of the pointing-selective regions PRR n pprr, extening from the precuneus to the superior prietl loule, mtches the locliztion of pointing-selective ctivity in other neuroimging stuies 7,8, s well s the reltive position of puttively homologous reching-specific regions in the mcque monkey (PRR, meil intrprietl re n re V6A) 24. Similrly, the loction of the scce-selective region pips, in the posterior spect n meil nk of the intrprietl sulcus, is consistent with the locliztion of topogrphiclly selective region tht is responsive to eye movements n sptil ttention in humns 7,11, This region shows, consistent with previous work, weker scce-specific preprtory signls 7 ut strong selectivity uring execution. This region represents the puttive homolog of mcque LIP, which lso show similr response properties 1,12. Secon, two out of three regions (pprr n pips) respone more strongly when sujects selecte the preferre response uner conitions in which the stimulus i not provie ny useful informtion (5% sensory evience). Therefore, ctivity in these regions preicts motor ecision inepenently of ny sensory evience. This is consistent with recent reports of monkey s PRR neurons responing to spontneous choice of rm movements in the sence of instructing cues 28. Thir, these regions were sptilly selective in reltion to the trget loction or movement irection; tht is, the response uring the ecision ely ws stronger for contrlterl thn for ipsilterl trgets/movements. A sptilly selective response unerlies either selection of the trget stimulus or plnning of movement irection. Notly, effector n sptilly selective signls were inepenent n itively contriute to the response in these regions. This is consistent with results from oth the PRR n LIP regions in the monkey, in which sptil n effector-specific signls re lso lrgely inepenent from one nother 29,3. In summry, the comine functionl properties of our posterior prietl regions strongly inicte tht they contin the right mixture of signls (sensory evience, motor n sptil) for implementing simple ecision-mking mechnism on the sis of the continuous trnsformtion of sensory informtion into motor ecisions. In this cse, the ssocition etween stimuli n responses ws entirely ritrry n ws not tune to the sensory properties of n re. This result generlizes sic mechnism tht ws previously ientifie in mcques uring simpler perceptul ecisions 3,4 to more complex humn ecisions. However, the limite sptil resolution of fmri oes not llow us to istinguish whether these signls converge on the sme neuronl popultion or whether they re istriute over ifferent neuronl types or lyers in the sme region. Prietl versus frontl cortex In contrst with the strong ecision-relte signls in posterior prietl cortex, we foun reltively wek evience for ccumultion of sensory evience in frontl cortex. The pointing-selective FRR n the scceselective FEF region in premotor cortex were not moulte y either sensory evience levels or ecision outcome. The SMC showe wek effects of sensory evience n motor plnning ut no ecision outcome or sptilly selective moultion. Furthermore, in voxelwise nlysis to exmine the interction of sensory evience n response effector, we still foun significnt moultion (multiple comprison correcte z mp significnt t the cluster level of P ¼.5) of the pointing-selective PRR in posterior prietl cortex n of the primry SMC ut no effect in premotor or prefrontl cortex. This 6 ADVANCE ONLINE PUBLICATION NATURE NEUROSCIENCE

7 28 Nture Pulishing Group negtive fining must e weighe ginst single-unit evience of sensory ccumultion in orsolterl prefrontl cortex 31 n the limite sptil resolution of fmri in etecting iniviul neuronl popultions in the sme re. In contrst, prefrontl regions incluing ventrl n orsolterl cortex, nterior insul, n nterior cingulte showe strong moultion y sensory informtion inepenent of effector. However, this effect ws result of stronger responses for ifficult (for exmple, 5% evience) thn for esy (for exmple, 1% evience) stimuli, which cn e ttriute to either perceptul ifficulty or ttention lo ut not to sensory evience ccumultion. In summry, within the resolution of the fmri methos tht were use in this stuy, we cn conclue tht sensory-motor ecision mechnisms seem to e specific to posterior prietl cortex. Furthermore, the moultion of preprtory ctivity in SMC y sensory evience is consistent with continuous flow moels of ecision-mking in which sensory evience continuously flows from sensory to motor regions of the rin 32. Sensory-motor versus generl ecision-mking mechnisms The fct tht ecision signls were loclize in effector-specific regions, n tht no region in the rin showe positive moultion y level of sensory evience inepenent of response, rgues ginst the ie of generl strct ecision-mking mechnism postulte in tritionl psychologicl moels 1. Apreviousstuy 16 reporte signls tht scle with the level of sensory evience inepenently of motor responses in left superior prefrontl region. Sujects performe motion-iscrimintion tsk on isplys contining ifferent levels of coherent motion, similr to the originl monkey experiments 3,4, n reporte their ecision using either n eye movement or key press. The superior prefrontl region showe stronger response to high thn to low evience stimuli n no specificity for the type of movement. The positive moultion y sensory evience n the inepenence from motor plns were thought to support the evelopment of more generl ecision-mking moule to ccommote the roer rnge n greter flexiility of humn ecisions 2. This hypothesis conflicts with current evience in nonhumn primtes tht perceptul ecisions re closely tie to motor plns 3,4,31. With the limittion of compring responses cross stuies, we foun tht this prefrontl region is prt of more istriute network incluing lterl prietl cortex, posterior cingulte-precuneus n ventro-meil prefrontl cortex. This network correspons to the so-clle efult network 17,18, which is commonly ectivte uring gol-irecte ehvior n suppresse uring ifficult perceptul or ttentionl emning tsks 19,2. As the ectivtion is more profoun for ifficult (or low evience) thn for esier (or high evience) stimuli, irect contrst etween these two conitions (s in ref. 16) my yiel n pprent positive moultion y sensory evience. Conclusions To the est of our knowlege, this is the first report to show tht humn posterior prietl cortex contins sensory-motor mechnism for ritrry visul ecisions. Activity in posterior prietl cortex, specific for plnning effector-specific movements, ws moulte t the moment in which ecisions were eing forme y the level of sensory evience, the position of the trget n the outcome of the ecision in the sence of helpful sensory informtion. These signls represent the neurl correlte of mechnism, completely trine y the experimentl ssocition, y which sensory evience ccumultes towr the ehviorl outcome of n ritrry ecision. Moreover, in our hns, visul ecisions in humn sujects o not necessrily involve high-level representtions inepenent of sensory-motor systems 2,16. Rther, ecision processes seem to e emoie in the irect trnsformtions etween relevnt sensory n motor representtions, with premotor circuitries weighting sensory evience towr lerne ehviorl choices, consistent with n intentionl rchitecture of informtion flow 33. More generlly, these finings support the emerging ie of emoie cognition 34, in which strct cognitive functions o not epen on specilize moules ut re uilt on simpler sensory-motor processing mechnisms. More simply si, to see n ecie is, in effect, to pln motor response 35. METHODS Sujects. We otine written informe consent from the 12 helthy right-hne volunteers (8 femles, men ge 24.2) who prticipte in the stuy. The experimentl protocol ws pprove y the G. D Annunzio University of Chieti s institutionl ethics committee. Ech prticipnt complete psychophysicl clirtion session (performe insie the mgnetic resonnce scnner to ensure stle stimultion conitions) for iniviul selection of levels of sensory evience to e use in the ecision tsk, n fmri session of two loclizer scns to loclize effector-specific regions n two pssive view scns to mesure pssive sensory responses to fce n plce stimuli in these sme regions, 1-h trining session on the ecision tsk to lern the stimulus-response ssocition, n t lest two fmri sessions to perform the ecision tsk. Loclizer n pssive view scns. During ech loclizer scn, prticipnts lternte eight locks of elye pointing movements, sccic eye movements n fixtion every 16 s. During ech pssive view scn, prticipnts viewe eight lternting locks (16 s) of unmske fces n plces presente for 3 ms every 5 ms, interleve with fixtion perios of 15 s on verge. Psychophysicl clirtion. During the psychophysicl clirtion session (Fig. 1), fce/plce imge ppere centrlly for 3 ms every 2 s, with vrile mount of white noise superimpose, in squres of 8 8 pixels. Fce/ plce imges were pixel gry-scle igitize photogrphs selecte from lrger set evelope y N. Cohen (University of Illinois) n use in previous experiments Sujects respone y pressing one key for fces n one key for plces. We rnomly presente 2 trils for ech of 35 eqully spce noise levels, forming continuous rnge from unmske fces through pure noise to unmske plces. A proit nlysis of inomil responses se on mximum likelihoo estimtion 5,6 provie the threshol n slope of the psychometric function escriing the proility of giving plce response s function of the evience level in the imge. Interpoltion of the iniviul psychometric function llowe us to select five noise levels for ech iniviul, yieling %, 25%, 5%, 75% n 1% plce responses. Decision tsk. The ecision tsk (Fig. 1) inclue 2 scns of 24 trils ech. A fce/plce imge (t one of the five noise levels selecte uring clirtion) ws presente long with peripherl visul trget, fille white circle (.9-eg imeter) ppering in one of eight ril loctions (1/8, 3/8, 5/8, 7/8, 9/8, 11/ 8, 13/8 or 15/8 p) t 4 eg eccentricity. After ely, sujects reporte whether they h seen fce or plce y performing n eye or pointing movement, respectively, towr the rememere position of the peripherl trget. Dt nlysis. Functionl imges were nlyze on voxel y voxel sis ccoring to the generl liner moel. ROIs were ientifie from single suject z mps of contrsts 39 from the loclizer scns n use for inepenent time series nlysis uring the ecision experiment. Hemoynmic responses in the ecision experiment were estimte without ny shpe ssumption t the voxel level using the generl liner moel 4 n verge cross ll the voxels of ech ROI to generte regionl time series. Iniviul time points of ech estimte hemoynmic response, either on the regionl t or t the single voxel, were entere into group nlyses conucte through rnom-effect ANOVAs juste for correltions cross time points 41, in which the experimentl fctors, incluing sensory evience, response effector n visul fiel, were crosse with the time fctor. Seprte ANOVAs were conucte on the ely NATURE NEUROSCIENCE ADVANCE ONLINE PUBLICATION 7

8 28 Nture Pulishing Group n execution phses of the ecision tsk (six time points ech). Aitionl etils re given in the Supplementry Methos online. Note: Supplementry informtion is ville on the Nture Neuroscience wesite. ACKNOWLEDGMENTS We re grteful to E. Lomri for her ssistnce in t collection. We lso thnk C. Lewis n C. Sestieri for technicl support on t nlysis, n A. Snyer, M. McAvoy n E. Akuk for softwre n hrwre evelopment. This work ws supporte y the EU FP6-MEXC-CT project (Investigtions in Brin Sciences Euction Network), US Ntionl Institute of Mentl Helth grnt R1MH n US Ntionl Institutes of Helth grnt NS4813 to M.C., y Itlin Ministry of University n Reserch grnt PRIN _4 to G.G., n y the 3r Ph.D. Interntionliztion Progrm of the Itlin Ministry of University n Reserch. AUTHOR CONTRIBUTIONS A.T., G.G. n M.C. were involve in experimentl esign. A.T. ws responsile for t cquisition n t nlysis, n A.T., G.G., G.L.R. n M.C. were involve in t interprettion n writing the mnuscript. 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Vision Res. 41, (21). 8 ADVANCE ONLINE PUBLICATION NATURE NEUROSCIENCE