The Engagement of Mid-Ventrolateral Prefrontal Cortex and Posterior Brain Regions in Intentional Cognitive Activity

Transcription

1 Human Bain Mapping 29: (2008) The Engagement of Mid-Ventolateal Pefontal Cotex and Posteio Bain Regions in Intentional Cognitive Activity Anja Dove, 1 Tom Manly, 1 Russell Epstein, 2 and Adian M. Owen 1 * 1 Medical Reseach Council Cognition and Bain Sciences Unit, 15 Chauce Road, Cambidge CB2 7EF, UK 2 Cente fo Cognitive Neuoscience, Univesity of Pennsylvania, Philadelphia, Pennsylvania Abstact: It is now widely ecognized that cognitive pocesses ae caied out by a distibuted netwok of bain aeas, some of which ae involved in peceptual pocessing of a stimulus, whilst othes ae involved in cognitive contol pocesses equied to cay out cetain tasks. In this study, diffeential contibutions of highe visual aeas and of an aea involved in cognitive contol pocesses wee investigated in a task equiing paticipants to simply look at a stimulus o to look with the intention of emembeing. Vaying the extent to which intentional cognitive pocesses wee equied and the stimulus mateial in this task allowed the analysis of top-down and bottom-up influences on these aeas, espectively. Significant inceases in the mid-ventolateal pefontal cotex (mid-vlpfc) wee only obseved when the stimuli wee viewed with an intention in mind, iespective of the stimulus type. In contast, activity in the paahippocampal place aea and the fusifom face aea, was only modulated in conditions equiing intentional contol when stimuli wee pesented that also elicited activity in these egions duing passive viewing. These findings help to claify the complimentay ole that the mid- VLPFC and posteio highe visual aeas play in contolled and elatively automatic memoy pocessing. Hum Bain Mapp 29: , VC 2007 Wiley-Liss, Inc. Key wods: pefontal; ventolateal; contol; executive; encoding; ecognition; fusifom face aea; paahippocampal place aea; anteio insula; fmri INTRODUCTION *Coespondence to: Adian M. Owen, MRC Cognition and Bain Sciences Unit, 15 Chauce Road, CB2 7EF Cambidge. adian.owen@mc-cbu.cam.ac.uk Received fo publication 6 Apil 2006; Revised 29 Novembe 2006; Accepted 18 Decembe 2006 DOI: /hbm Published online 16 Mach 2007 in Wiley InteScience (www. intescience.wiley.com). The distinction between contolled pocesses enabling us to cay out actions intentionally, with delibeate conscious contol [Noman and Shallice, 1986] and automatic pocesses not equiing such contol has been an impotant one in majo aeas of psychology (e.g. memoy: [Baddeley and Della Sala, 1996], attention: [Noman and Shallice, 1986], cognitive development: [Flavell, 1976]). It has long been agued that the pefontal cotex is involved in contol pocesses [Noman and Shallice, 1986]. In functional imaging studies, mid-ventolateal pefontal cotex (mid- VLPFC), dosolateal pefontal cotex and anteio cingulate have consistently shown activity in conditions with contol demands [Duncan and Owen, 2000]. Howeve, thee is evidence that activity in moe posteio aeas is also enhanced when contol pocesses ae equied [Dove et al., 2000]. This could be because fontal and cetain posteio egions fom pat of a netwok equied fo effotful tasks [Dehaene et al., 1998] in which case it VC 2007 Wiley-Liss, Inc.

2 Dove et al. could be difficult to establish diffeential (i.e. functionally specific) fontal lobe involvement. Altenatively, contol pocesses that ae elatively nonspecific with espect to stimulus type, which ae pedominantly fontal in oigin, may have seconday effects on posteio aeas that ae elated to the paticula task at hand. Of couse both possibilities could apply in diffeent contexts. To look at these issues in the context of a specific task we adapted a peviously epoted paadigm [Dove et al., 2006] to investigate diffeential involvement of mid-vlpfc and highe visual aeas in contol pocesses. The mid-vlpfc was chosen fo the following easons. This egion - speading fom the oute suface along the fontal opeculum to become continuous with epoted activations in the anteio insula, close to the coodinates 41, 20, 0 and 37, 20, 3, [Duncan and Owen, 2000] - has shown activity in a boad ange of tasks equiing contol pocesses, fom attention [Duncan and Owen, 2000], memoy [Owen, 2000] and task switching [Dove et al., 2000] to less fequently studied tasks such as choosing a dinne date [Tuk et al., 2004] and lying [Langleben et al., 2005], i.e. a ange of tasks with diffeent stimuli and contexts. To explain this vaiety it is necessay eithe to posit many sepaate and elatively specific pocesses in close anatomical poximity within the mid-vlpfc o a moe geneal pocess that is equied in many tasks. One example of the second view is Petides hypothesis that the mid-vlpfc may be involved in vaious executive pocesses deived fom the subject s plans and intended actions and opeate on infomation available in the posteio association cotical aeas whee peceptual and basic shot- and long-tem mnemonic pocessing occus ([Petides, 1994], p 73). Inteestingly, he also suggested that in situations in which incoming o ecalled stimuli automatically tigge stoed epesentations, without any explicit conscious contol, the mid-vlpfc will not play a majo ole ([Petides, 1994], p 73). Accoding to this hypothesis, passive viewing of stimuli should elicit little if any mid-vlpfc activity when compaed with a baseline condition. To ou knowledge, this hypothesis has not been tested yet. Unlike the mid-vlpfc, highe visual aeas such as the fusifom face aea (FFA) and the paahippocampal place aea (PPA) ae clealy modulated by stimulus type. Pevious liteatue has shown that FFA and PPA activity is elicited by faces [Kanwishe, 2000; Tong et al., 2000] and scenes [Epstein and Kanwishe, 1998], espectively, even duing passive watching of these stimuli [Epstein and Kanwishe, 1998; Kanwishe et al., 1997]. On the othe hand, activity in these egions has also been shown to be modulated by instuctions to attend to o memoize such stimuli [Vuilleumie et al., 2001; Wojciulik et al., 1998]. This suggests that, in a manne simila to the mid-vlpfc, activity in these aeas may be modulated by intention. It is cuently unclea whethe intentional pocessing only affects PPA and FFA activity if stimuli ae pesented that would elicit activity in these aeas duing passive viewing. Although it is unclea whethe diect anatomical connections exist between the mid-vlpfc, the PPA and the FFA in humans, in nonhuman pimates it is known that visuospatial and object vision aeas in the paietal and tempoal lobes inteact closely with the ventolateal fontal cotex (Petides, 1994). Specifically, VLPFC egions have diect long-ange pojections to and fom posteio visual association cotices, which includes both the FFA and the PPA [Petides, 1994; Ungeleide et al., 1989]. A ecent study by Petides and Pandya [2002] suggests futhe that aea 47/ 12, occupying the most vental pat of the ventolateal pefontal cotex of the macaque, has simila cytoachitectonic chaacteistics to Bodmann aea 47 in humans. It is likely, theefoe, that Bodmann aea 47 in the human has simila diect anatomical links with these infeotempoal egions, simila to those that ae known to exist in the macaque. The mid-vlpfc egion of inteest in the cuent study coesponds vey closely with Bodmann aea 47 in the human, as descibed by Petides (1994). To help claify the oles of mid-vlpfc and FFA, and PPA in conditions with high and low demands on intentional contol, we utilized a peviously epoted paadigm that elicited obust activity in mid-vlpfc [Dove et al., 2006]. Thee diffeent types of stimuli, faces, scenes, and coloful abstact paintings (i.e. not epesentational of faces o scenes) wee pesented unde the following conditions (Fig. 1). In two conditions designed to have low equiement fo contolled, intentional pocessing stimuli wee pesented with the simple instuction look at this. Within this, in the low intention encoding condition a pictue was shown fo the fist time. In low intention eviewing condition a peviously pesented pictue was shown again. The emaining two conditions wee designed to have inceased demands on contol pocesses. Hee, explicit task instuctions ( emembe this and have you seen this? ) wee given. Remembe this equied voluntees to emembe a new pictue as best they could, and have you seen this? equied them to indicate whethe a given pictue had been pesented peviously o not. Abstact paintings wee included patly to eplicate the specific effects epoted in the pevious study and patly as visual stimuli that had a simila salience level to the face and scene pictues, but wee less likely to elicit inceased activity in the FFA o PPA. We expected that the cuent expeiment would allow us to obseve diffeential involvement of mid-vlpfc and highe visual aeas depending on whethe demands to cay out intentional pocessing wee high (in the high intention conditions ) o low (in the low intention conditions ) and depending on the stimuli that wee pesented. By including encoding and ecognition conditions it was possible to investigate whethe simila pattens of activity occu in diffeent types of tasks. Moe specifically, the following set of clea pedictions could be tested: 1. Effect of intention. Regadless of stimulus o task type, mid-vlpfc activity will always show moe activity in conditions with high demands on intentional pocessing (the high intention conditions ) compaed with conditions with low demands on intentional pocessing 108

3 Engagement of VLPFC in Intentional Pocesses Figue 1. Expeimental design. Abstact paintings, faces and scenes wee pesented shotly afte an instuction. In the instuction, voluntees wee asked to look at the stimuli ( low intention encoding and low intention eviewing ), to delibeately encode the stimuli ( high intention encoding ) o to decide whethe a stimulus has been pesented peviously ( high intention ecognition ). See Mateials and Methods fo details. (the low intention conditions ). In contast, activity in PPA and FFA will only show moe activity in conditions with high demands on intentional pocessing compaed with conditions with low demands on intentional pocessing, if these aeas show activity duing passive watching of the stimuli in the low intention conditions compaed with baseline (blank sceen). 2. Effect of stimulus type. Thee will not be an effect of stimulus type on the mid-vlpfc, wheeas PPA and FFA will show most activity wheneve thei pefeed stimulus is pesented (i.e. scenes and faces, espectively). 3. Activity elicited by passive viewing. Thee will be little, if any, mid-vlpfc activity duing passive viewing of stimuli (in the low intention conditions ) compaed with baseline (blank sceen). On the othe hand, passive viewing of thei pefeed stimulus will elicit activity in the PPA and FFA compaed with baseline (blank sceen). MATERIALS AND METHODS Voluntees Seventeen ight-handed healthy young adults paticipated in the imaging study. The data of thee voluntees could not be analysed because of excessive movements duing scanning. Following the scanning session each voluntee was asked about thei pefomance of the task. One paticipant said that he had not tied to emembe the stimuli in the emembe this condition, because he thought that this was not necessay fo subsequent ecognition. His esults wee theefoe excluded fom futhe analysis. Theefoe data of 13 voluntees wee included in the analyses (nine male, fou female, yeas of age). The study eceived ethical appoval fom the Cental Oxfod Reseach Ethics Committee. Infomed witten consent was obtained fom all voluntees in accodance with the Declaation of Helsinki. Stimuli and Task Paametes In the localize scans, digitized gayscale photogaphs of faces, common objects, indoo scenes and two othe object categoies not elevant fo this expeiment wee pesented. The length of each scan was 6 min and 15 s. Each scan was divided into 20, 15-s long pictue epochs (fou fo each of the stimulus categoies) inteleaved with five epochs duing which only a fixation point was pesented. In each epoch, 20 photogaphs fom the same categoy wee pesented fo 300 ms each with an intestimulus 109

4 Dove et al. (A) Beta values obseved in the left and ight ventolateal pefontal cotex, the fusifom face aea and the paahippocampal place aea duing high intention and low intention encoding and ecognition (e-viewing) of paintings (p), faces (f), and scenes (s). The high Figue 2. intention conditions ae pesented in dak gey and the low intention conditions in light gey. Eo bas show the standad eo of the mean. (B) Examples of the stimuli used in the expeiment (note that the stimuli wee pesented in colo in the expeiment). inteval of 450 ms. The task of the voluntee was to pess a button wheneve two identical stimuli appeaed in a ow (1-back task). Thee wee two such stimulus epetitions pe epoch. Epoch ode was countebalanced as descibed peviously [Epstein et al., 1999; Epstein and Kanwishe, 1998]. In the expeimental task coloful abstact paintings, faces, and scenes wee used as stimuli (Fig. 2). The abstact 110

5 Engagement of VLPFC in Intentional Pocesses paintings wee collected fom web sites of amateu atists. Paintings wee chosen that did not contain easily ecognizable objects o faces. The face stimuli wee colo potait photogaphs of men and women taken against a white backgound ([Matinez and Benavente, 1998], vl1.ecn.pudue.edu/~aleix/aleix_face_db.html). Scenes wee colo photogaphs of landscapes. Most scenes did not contain any pominent object (such as a single tee o an animal in the foegound). Since some stimuli may be moe easily ecognizable than othes, stimuli wee andomly assigned to the high intention and low intention conditions fo each voluntee (fo instance a paticula stimulus could be pesented duing low intention encoding fo one voluntee but duing high intention encoding fo anothe voluntee). Befoe evey tial, an instuction was pesented fo 1.5 s, followed by a 0.4 s delay and the pesentation of painting, face o scene fo 3 s (Fig. 1). Afte a futhe inteval of 0.4 s the next tial began. In the low intention encoding condition the instuction was look at this. This instuction indicated that the voluntee s task was just to look at the stimulus that followed (72 tials altogethe, 24 of each stimulus type). In the high intention encoding condition voluntees eceived the instuction emembe this. The task was to emembe the stimulus that followed (72 tials altogethe, 24 of each stimulus type). In the high intention ecognition condition the instuction was have you seen this? Hee, the voluntee was equied to decide whethe he o she had seen the stimulus befoe o not. In some tials, stimuli that had been shown in the high intention encoding condition wee pesented (72 tials altogethe, 24 of each stimulus type). In this case, the coect answe was to indicate that the stimulus had been seen befoe. In othe tials new stimuli wee shown (48 tials altogethe, 16 of each stimulus type). The coect answe was to indicate that the stimulus had not been seen befoe. Note that voluntees wee only asked to ecognize old stimuli that had been shown in the high intention encoding condition to discouage the voluntees fom intentionally encoding the stimuli in the low intention encoding condition (contay to the instuction). A futhe condition was constucted to contol fo the fact that stimuli in the high intention ecognition condition wee being viewed moe than once and to examine, as fa as is possible, ecognition memoy in the absence of a specific task instuction. Thus in the low intention eviewing condition, voluntees eceived the instuction look at this. Aftewads stimuli wee pesented that had peviously been shown in the low intention encoding condition (72 tials altogethe, 24 of each stimulus type). Additionally, non-events wee pesented in which the sceen was blank fo 5.3 s (72 tials). This condition seved to assess BOLD signal intensity duing a shot esting baseline. The expeiment was 36 min long. It was pesented in two blocks of 18 min each. In all conditions, except the non-events, esponses wee made. Voluntees wee instucted to pess two buttons simultaneously with thei index and middle finges duing the low intention encoding, high intention encoding and low intention e-viewing conditions. In the high intention ecognition condition voluntees wee instucted to only pess one button with thei index finge to indicate that they had seen the painting befoe. They wee asked to pess anothe button with the middle finge, if they decided that the painting had not been pesented befoe. All tials wee pesented andomly with the following constaints: Stimuli that wee shown seveal times wee fist shown in the low intention o high intention encoding conditions and aftewads in the low intention e-viewing and high intention ecognition conditions, espectively. Stimuli that wee epeated e-occued within the next tials. Thee wee no moe than thee tials with the same instuction in a ow. Image Acquisition and Analysis Scanning was caied out at the Cente fo Functional Magnetic Resonance Imaging of the Bain (FMRIB), Oxfod, UK on a 3 Tesla MRI system diven by a Vaian Unity Inova console and equipped with an Oxfod Magnet Technology magnet, a Siemens body gadient coil and a bid-cage adio-fequency head coil built by Enzo Babei (Robats Reseach Institute, Canada). An In Focus LP1000 pojection system (Unicol Engineeing, Oxfod, UK) was used to poject the stimuli onto a white sceen located at the foot end of the scanne bed. Subjects could view this sceen by weaing a pai of pism spectacles (Waday-Pemise Engineeing, Suey, UK) duing scanning. Subjects esponses wee made using two specified buttons ( left and ight ) on a fou-button esponse box held in the ight hand. Foam padding was utilised to educe paticipant movements in the scanne within the MRI head coil. Fo functional data, an echo plana imaging (EPI) pulse sequence was implemented to acquie T2*-weighted image volumes with blood oxygen level dependent (BOLD) contast. Each volume consisted of 21 slices with a voxel size of 3 4 6mm 3 (TR ¼ 3s,TE¼ 30 ms, flip angle of 90, FOV: , matix size: 64 64). A map of the magnetic field was acquied and then used to coect fo distotion to the EPIs esulting fom inhomogeneities in the field [Cusack and Papadakis, 2002; Jezzad and Balaban, 1995]. This pocedue has been shown to impove anatomical localization and incease the powe of goup studies by achieving bette spatial egistation between the data fom diffeent subjects [Cusack et al., 2003]. The field map was always acquied diectly befoe o afte the acquisition of the functional data to ensue that the head position of the voluntee was maximally compaable. A high esolution T1 stuctual scan was acquied (voxel size: mm 3 ) eithe in the same scanning session o on a diffeent day. SPM99 softwae was used fo pepocessing and statistical analyses ( The fist five vol- 111

6 Dove et al. Figue 3. Peak activity in the mid-ventolateal pefontal cotex o anatomically close to the mid-ventolateal pefontal cotex in studies with diffeent cognitive demands, ovelaid onto a nomalized and aveaged stuctual image in MNI space (MNI 152 image fom the SPM distibution). The figue was ceated using MRIco by Pof. Chis Roden. Refeences 1 7 efe to Table I. umes of the EPIs wee discaded due to T1 satuation effects. Afte ealignment of the data slice timing coection was caied out. The field map infomation was used to coect fo distotions in the phase-encode diections of the EPIs using an SPM [Cusack and Papadakis, 2002; Cusack et al., 2003]. The EPIs wee nomalized by using a masked EPI to EPI template nomalization [Bett et al., 2001] and smoothed with an 8 mm Gaussian kenel. A egion of inteest (ROI) appoach was used to analyse the data. To define the ROI in the PPA and FFA, we followed the appoach developed by Kanwishe and othes [Kanwishe et al., 1997] and Epstein and Kanwishe [Epstein and Kanwishe, 1998]. ROI wee defined individually fo each voluntee using data fom the localize scans, which wee analyzed using a geneal linea model as implemented in SPM99. Fo each scan, the esponse at each voxel was modeled using an 11-egesso model in which the fist five egessos modeled the esponse to each of the five stimulus types as boxca function convolved with a canonical hemodynamic esponse function, and the next six egessos modeled motion-specific effects. Data was tempoally filteed befoe analysis to emove low-fequency confounds. Linea contasts wee used to identify clustes of contiguous voxels in the occipital tempoal egion that esponded moe to (1) scenes compaed with objects (candidate PPA voxels) and (2) faces compaed with objects (candidate FFA voxels). As we wished to distinguish between the functional esponse in egions that wee spatially vey poximate, we used a paticulaly stingent definition of the PPA and FFA, which we defined fo each voluntee by eithe choosing the voxel with peak activity o, if thee wee seveal peak voxels that wee similaly active, the voxel that was closest to the mean MNI coodinates of all voluntees in that egion. Note that because of the spatial smoothing of the functional data of the main expeiment, each peak voxel tanslates into an 8-mm-wide FWHM Gaussian ROI. Fo the mid-vlpfc, a diffeent appoach had to be taken because no established localize task exists to define paticipant-specific ROIs in these aeas. To this end, ROIs wee defined using data fom a pevious study [Dove et al., 2006]. A andom effects goup analysis was caied out contasting conditions in which paticipants wee asked to intentionally encode o ecognize abstact paintings with conditions in which the viewing of abstact paintings was passive i.e. the identical manipulation to that used in the cuent study albeit with only abstact painting stimuli. The esults showed inceased mid-vlpfc activation in the high-intention condition. ROIs fo the cuent study wee geneated by dawing 7 mm sphees aound the peaks using the MARSBAR tool [Bett et al., 2002]. These sphees wee somewhat smalle than the whole activation cluste, to ensue that only voxels with elatively high t-values would be chosen in the cuent expeiment. Note that we choose a sphee hee athe than a single voxel because the ROI could not be defined fo each voluntee individually, as in the FFA and PPA. Choosing a lage ROI makes it moe likely that the ROI of an individual voluntee contains voxels that show activity in the expeimental conditions. The MNI coodinates of the peak activation wee 36, 22, 4 in the ight mid- VLPFC and 36, 16, 4 in the left mid-vlpfc (Fig. 3). A geneal linea model was applied to the functional data of each voluntee [Fiston et al., 1995]. The model included covaiates fo sustained neuonal esponses elicited duing high intention encoding of paintings, faces and scenes. Similaly thee wee sepaate covaiates fo the thee stimulus types in the conditions high intention ecognition of peviously pesented stimuli, high intention ecognition of new stimuli, low intention encoding and low intention e-viewing of stimuli shown fo the second time. The onsets of events wee at the time the instuction was shown. The duation of the events was the whole tial duation (5.3 s). A boxca function convolved with a ca- 112

7 Engagement of VLPFC in Intentional Pocesses nonical hemodynamic esponse was used to model these events. Additionally six motion paametes deived duing ealignment wee used to coect fo esidual movement atefacts. The non-event condition was modeled implicitly. This had the advantage that the signal intensity in the nonevent condition was set to 0. A high-pass filte with a cut-off of 250 s was employed to coect fo low fequency difts in BOLD-signal. No global scaling was used. Paamete estimates fo each covaiate wee calculated fom the least mean squaes fit of the model to the data. The beta values of all covaiates wee extacted fo each ROI fo each voluntee using the MARSBAR tool [Bett et al., 2002]. Only the beta values of the covaiates fo all high intention and low intention encoding conditions, the covaiates fo high intention ecognition of peviously seen pictues and the covaiates fo low intention e-viewing wee analysed futhe. Data wee enteed into SPSS. RESULTS Behavioal Results In the task paticipants viewed abstact pictues, faces o scenes with eithe the intent to emembe them o to simply view them. They also saw again stimuli fom both of these conditions but wee only asked to make an explicit judgement concening thei ecognition of stimuli shown in the high-intention ( emembe this ) conditon. In this espect, the accuacy of thei esponses wee tansfomed into d -measues fo each voluntee [Macmillan and Ceelman, 1991]. This gives a measue of pefomance that is independent of esponse bias. Data wee then aveaged ove paticipants. The esulting values in the high intention ecognition condition wee 2.73 (paintings), 2.86 (faces) and 2.97 (scenes). One-tailed t-tests testing against 0 showed that pefomance was significantly geate than chance in all thee conditions (paintings: t(12) ¼ 12.06, P < ; faces: t(12) ¼ 15.72, P < ; scenes: t(12) ¼ 13.09, P < ). A epeated measues analysis of vaiance was conducted with the facto stimulus mateial. This test showed that thee was no significant effect of mateial type (F(2,24) ¼ 1.18, P ¼ 0.32). By definition no behavioal data fom the low intention memoy conditions wee available fom the fmri study. Howeve, an initial pilot expeiment using abstact paintings only [Dove et al., 2006] showed that, as pedicted, high intention encoding leads to significantly bette subsequent ecognition than low intention encoding. Recognition fo pictues was howeve well above chance even if the stimuli wee pesented once in the low intention encoding condition suggesting as might be expected that some encoding was taking place. Localize task FMRI Results PPA could be identified in 13 out of 13 voluntees in the ight hemisphee and FFA could be identified in 11 out of 13 voluntees in the ight hemisphee. 1 The mean MNI coodinates in the ight PPA wee 30, 46, 10 and in the ight FFA 42, 52, 20. In addition, the PPA could be identified in the left hemisphee in 13 out of 13 voluntees. The mean coodinates in the left PPA wee 26, 49, 10. Note that ou finding that PPA could be identified bilateally and FFA in the ight hemisphee only is consistent with the liteatue [Kanwishe et al., 2001]. Main expeiment Fo each ROI an ANOVA was computed with the factos intention, stimulus type, and task. The significance level was Futhemoe we examined whethe the b-values in the six low intention conditions diffeed significantly fom 0. Since the baseline level of activity was set to 0, these tests could establish whethe thee was any activity in a given low intention condition compaed with the baseline task (looking at a blank sceen). Because 6 tests wee caied out, the coected significance level of was used (Bonfeoni coection) fo all ROIs except the left and ight mid-vlpfc. In this aea we expected no significant activity in the low intention conditions compaed with baseline, and theefoe wished to use the moe libeal significance level of Left mid-vlpfc As can be seen in Figue 2, signal intensity in the left mid-vlpfc was highe when paticipants viewed stimuli with the intention of emembeing and with the intention of ecognizing compaed with paallel conditions in which they wee asked to passively view the stimuli. Accodingly, the main effect of the facto intention eached significance (F(1,12) ¼ 35.32, P < 0.05) in the ANOVA. Thee wee no othe significant main effects o inteactions. Notably, theefoe, activity in this egion was not sensitive to stimulus type. In line with ou pedictions, thee was no significant activity in the low intention conditions compaed with baseline at the 0.05 significance level (t(12) < 1.608, P > 0.05) with the exception of the low-intention eviewing of scenes (t(12) ¼ 2.721, P < 0.05). A t-test against 0 fo all low-intention conditions combined was not significant at the 0.05 significance level (t(12) ¼ 1.79, P ¼ (two-tailed)). 1 The MNI-coodinates of the ROIs of each voluntee wee as follows: , , , , , , , , , , in the ight FFA, , , , , , , , , , , , , in the ight PPA and , , , , , , , , , , , , in the left PPA. 113

8 Dove et al. Right mid-vlpfc The esults in the ight mid-vlpfc wee vey simila (Fig. 2). Again signal intensity was highe in the high intention condition compaed with the low intention conditions. In the ANOVA thee was a main effect of intention (F(1,12) ¼ 27.92, P < 0.05). Again activity in this egion was not sensitive to stimulus type. Thee was no activity in any of the six low intention conditions compaed with baseline (t(12) < 1.627, P > 0.05). A t-test against 0 fo all low-intention conditions combined was not significant (t(12) ¼ 0.55, P ¼ 0.59 (twotailed)). Right FFA As expected, the main effect of stimulus type in the ANOVA was significant (F(2,20) ¼ 41.36; P < 0.05, Fig. 2). Faces elicited moe activity in this aea than paintings and scenes. Two othe main effects eached significance: intention (F(1,10) ¼ 7.35, P < 0.05) and task (F(1,10) ¼ 10.88; P < 0.05): Thee was moe activity in the FFA in the high intention conditions compaed with the low intention conditions, and moe activity in the encoding conditions compaed with the ecognition/e-viewing conditions. A significant inteaction of intention and task was obseved (F(1,10) ¼ 7.36, P < 0.05). To explain this inteaction, data of the stimulus type conditions wee combined. Two posthoc t-tests wee caied out, Bonfeoni coected fo multiple compaisons at (two-tailed). High intention encoding elicited moe activity than low intention encoding (t(10) ¼ 2.87; P < 0.025), wheeas activity duing high intention ecognition did not diffe fom low intention eviewing (t(10) ¼ 1.90; P > 0.025). Thee was activity in each of the six low intention conditions compaed with looking at a blank sceen (t(10) > 3.280; P < ), Fig. 2). Thus, FFA showed activity duing low intention encoding and e-viewing of faces, as pedicted, but also duing low intention encoding and eviewing of paintings and scenes. Left PPA Figue 2 shows that, as pedicted, signal intensity in the left PPA was highest wheneve scenes wee pesented. Thus, thee was a main effect of stimulus type (F(2,24) ¼ 39.56, P < 0.05) in the left PPA. In addition the facto task eached significance (F(1,12) ¼ 7.31, P < 0.05) activity duing encoding was on the whole highe than duing ecognition/e-viewing. Thee wee two inteactions: intention and stimulus type (F(2,24) ¼ 7.94, P < 0.05) and stimulus type and task (F(2,24) ¼ 5.85, P < 0.05). Thee post-hoc t-tests wee caied out to explain the intention and stimulus type inteaction. Data fom the high intention encoding and ecognition conditions and the low intention encoding and e-viewing conditions wee combined fo each stimulus type and task condition. Only when scenes wee shown, signal intensity in the high intention conditions (high intention encoding and ecognition combined) was highe than in the low intention conditions (low intention encoding and e-viewing combined), as pedicted (t(12) ¼ 4.09; P < one-tailed). Left PPA signal intensities duing high intention and low intention pocessing of faces (t(12) ¼ 1.01, P > 0.017) and high intention and low intention pocessing of paintings (t(12) ¼ 0.49; P > 0.017) did not diffe significantly. Thee futhe post-hoc tests wee caied out to explain the stimulus type and task inteaction. Data of high and low intention encoding and high and low e-viewing/ecognition wee combined fo each stimulus type and task condition. Activity duing encoding and ecognition of scenes diffeed significantly fom each othe (t(12) ¼ 3.39; P < 0.017); but this was not the case fo paintings (t(12) ¼ 2.26; P > 0.017) and faces (t(12) ¼ 0.68; P > 0.017). All low intention conditions in which scenes wee pesented diffeed significantly fom baseline (t(12) > 4.469; P < (one-tailed), Fig. 2), as pedicted. None of the othe low intention conditions eached significance in the one-sample t-tests (t(12) < 1.621; P > 0.008). Right PPA The esults of the ight PPA wee vey simila to the esults in the left PPA (Fig. 2). Thee was a main effect of stimulus type (F(2,24) ¼ 65.28; P < 0.05) and task (F(1,12) ¼ 9.75; P < 0.05), an intention * stimulus type inteaction (F(2,24) ¼ 7.30, P < 0.05) and a task * stimulus type inteaction (F(2,24) ¼ 9.26; P < 0.05). The intention * stimulus type inteaction can be explained by a significant diffeence in activity between high intention and low intention pocessing of scenes, as pedicted (t(12) ¼ 3.22, P < (one-tailed)), and no diffeence between high and low intention pocessing fo faces (t(12) ¼ 0.28; P > 0.017) o paintings (t(12) ¼ 0.78; P > 0.017). Regading the task * stimulus inteaction, it was again the case that signal intensity in the ight PPA was significantly highe duing encoding of scenes compaed with ecognition of scenes (t(12) ¼ 4.33; P < 0.017). Thee was no such effect fo faces (t(12) ¼ 0.90; P > 0.017) and paintings (t(12) ¼ 1.76; P > 0.017). As pedicted, low intention encoding and e-viewing of scenes elicited significant activity compaed with baseline (t(12) > 5.79; P < (one-sided)). Futhemoe thee was activity duing low intention encoding of paintings compaed to baseline (t(12) ¼ 3.64; P < 0.008). None of the othe conditions eached significance in the one-sample t-test (t(12) < 2.68; P > 0.008). DISCUSSION Summay In a egion of inteest analysis, the patten of activity in the mid-vlpfc egion was clealy distinguishable fom 114

9 Engagement of VLPFC in Intentional Pocesses the pattens of activity in the analysed posteio bain egions. Fistly, this bain aea was only significantly active in the high intention conditions compaed with the low intention conditions, wheeas the PPA and FFA showed significant activity in low intention conditions in which voluntees wee simply asked to just look, compaed with baseline. Secondly, the task instuction was the only facto that modulated activity in this aea, wheeas othe factos such as stimulus type, task type o stimulus epetition did not show any effect. In contast to the patten of activity in the mid-vlpfc, FFA and PPA activity was not only modulated by the task instuction but also by stimulus and task type. FFA and PPA showed most activity wheneve faces and scenes wee pesented espectively. Both FFA and PPA showed less activity when stimuli wee shown duing ecognition compaed with encoding. FFA and PPA activity was only modulated in conditions equiing intentional contol if the stimuli pesented wee of a type that elicited activity in these egions duing passive viewing. Mid-VLPFC Activity In functional imaging, it is statistically difficult to demonstate convincingly that an aea is not active and, pehaps as a esult of this, eseach on pefontal aeas has focussed on conditions that activate these egions athe than those that do not. Howeve, the conditions unde which a egion is not active ae potentially as infomative in consideing its function(s) as those in which it is. Theefoe we wished to investigate whethe thee is mid-vlpfc activity in the low intention conditions compaed with baseline. In a whole bain analysis thee may be insufficient powe to detect eal activity in an aea, due to coected thesholds fo multiple compaisons. Thus it can always be agued that thee may be sub-theshold activity. To maximize the possible sensitivity of this study in this espect, we employed an ROI appoach. The esults suggest that the mid-vlpfc was no moe engaged by the pesentation of faces, scenes o abstact paintings than simply looking at a blank sceen - despite othe egions being highly activated by these stimuli (see below) - when thee was no specific instuction to do something with those stimuli. This is consistent with the agument that this mid-vlpfc egion is not involved in situations in which stimuli automatically tigge stoed epesentations, without the necessity fo explicit conscious contol pocesses ([Petides, 1994, p 73). A simila point has been made moe ecently by Bunge [2004]. Accoding to this famewok VLPFC is involved in pocessing ules that guide ou behavio and is not needed wheneve wellleaned ules can be etieved automatically ([Bunge, 2004], p 575). The mid-vlpfc showed highe signal intensity in the high intention conditions compaed with the low intention conditions. Whilst this finding could be due to diffeences in esponse selection duing ecognition (voluntees have to select a esponse in the high intention ecognition condition, but pess two buttons duing the low intention eviewing condition), this hypothesis cannot explain the esults duing encoding. Theefoe, we suggest that this patten of activity eflects diffeences in cognitive contol pocesses between the conditions. In addition to the wok of Petides [1994] and othes, this esult ties in well with the view that the mid-vlpfc is activated unde a wide vaiety of conditions that equie contol pocesses (Fig. 3 and Table I; [Bave et al., 2003; Bunge et al., 2001; Cadoet et al., 2001; Cools et al., 2002; Dove et al., 2000, 2006; Duncan and Owen, 2000; Houde et al., 2000; Jenkins et al., 1994; Kostopoulos and Petides, 2003; Langleben et al., 2005; Tuk et al., 2004]). Note that the coodinates epoted in these studies ae anatomically vey close to the cente of ou egions of inteest in the mid-vlpfc (Fig. 3 and Table I). As pointed out in the intoduction, mid-vlpfc activity as defined in this pape speads fom the oute suface of the fontal opeculum to become continuous with epoted activity in the anteio insula [Duncan and Owen, 2000]. One of ou ROI, in the ight mid-vlpfc is moe clealy located in the fontal opeculum, wheeas the othe ROI is somewhat close to the anteio insula. Both ROIs, howeve, show the same patten of esults. One account is that activation that may appea to be in the anteio insula could in fact be slightly misplaced fontal opeculum activity. This would confom to mid-vlpfc, accoding to Duncan and Owen s definition [Duncan and Owen, 2000]. An altenative account is that the activity stems fom the anteio insula, which is showing the same modulatoy patten as the mid-vlpfc. It would be inteesting to claify this question in futue studies. In contast to findings in the FFA and PPA, mid-vlpfc activity was not modulated by stimulus type o task. This obsevation is consistent with findings in the liteatue (see eviews by [Bunge, 2004; Duncan and Owen, 2000; Owen, 2000]) and with the view that the VLPFC subseves athe geneal contol functions that may be needed in quite diffeent task contexts [Bunge, 2004; Duncan and Owen, 2000; Petides, 1994; Thompson-Schill et al., 2005]. In all conditions in which the mid-vlpfc was active the high intention conditions - thee was also a modulation of activity in the FFA o PPA, if the stimulus was of a type to which that egion was paticulaly sensitive. The act of paying paticula attention o attempting to encode appeas theefoe to be eflected in - o possibly patly enacted by - inceased activity in egions tuned to those stimuli even unde passive viewing conditions. This is consistent with the view that the VLPFC may modulate activity in posteio egions [Petides, 1994; Bunge, 2004]. Whilst it is difficult to specify these functions any moe clealy at pesent, it seems likely that the mid-vlpfc acts by biasing o tuning attentional pocessing between competing epesentations in modality-specific posteio egions in ode to maintain thei elevance to cuent behavioal goals [Dove et al., 2006]. Activity in posteio 115

10 Dove et al. TABLE I. Studies with peak activity in the mid-vlpfc o anatomically close to the mid-vlpfc. The table includes a task desciption, the coodinates in Talaiach and Tounoux (1988) o MNI space and a efeence numbe efeing to Figue 3 Task Study Coodinates Refeences Intention High intention encoding and etieval Based on Dove et al. 2006, 36, 16, 4 (MNI) 1 cente of ROIs in cuent study High intention encoding and etieval 36, 22, 4 (MNI) 2 Encoding Woking memoy load Bunge et al , 30, 4 (TAL) 2 Woking memoy load Bunge et al , 20, 4 (TAL) 5 Woking memoy load Bunge et al , 24, 4 (TAL) 6 Aay of two spatial Smith et al 1995 a 32, 18, 1 (TAL) 4 positions followed by ecognition pobe Retieval Retieval Cadoet et al , 28, 1 (TAL) 4 Retieval phase Kostopoulos and Petides , 22, 2 (TAL) 4 Reasoning Logical easoning/ovecome peceptual matching bias Houde et al , 16, 12 (MNI) 7 Decision making/pesonal choice Choosing dinne date Tuk et al , 23, 1 (TAL) 3 Choosing dinne date Tuk et al , 23, 1 (TAL) 4 Lying Concealing the identity of a cad Langleben et al , 22, 8 (TAL) 2 Concealing the identity of a cad Langleben et al , 19, 1 (TAL) 4 Novelty Eight-movement finge sequence Jenkins et al a 36, 20, 4 (TAL) 6 Response conflict Respond to lette with its own o diffeent lette name Taylo et al a 37, 17, 2 (TAL) 4 Taylo et al a 39, 17, 2 (TAL) 3 Task switching Task switching/esponse evesal Dove et al , 23, 8 (TAL) 6 Final evesal eo Cools et al , 24, 2 (MNI) 4 Task switching Bave et al , 30, 0 (TAL) 3 a Studies cited afte Duncan and Owen (2000). egions may eithe be enhanced in conditions equiing intentional contol, o, as suggested by Houde and colleagues [Houde et al., 2000], it may be necessay to inhibit peceptual biases oiginating in posteio cotex in ode to activate intentional contol pocesses. FFA and PPA Activity As expected, FFA showed most activity when faces wee pesented [Kanwishe et al., 1997] and PPA when scenes wee shown [Epstein et al., 1999]. This was the case when paticipants had a paticula activity to pefom with the stimulus and, as would be pedicted fom pevious wok, unde moe passive viewing conditions [Epstein and Kanwishe, 1998; Kanwishe et al., 1997]. PPA showed a significant incease in signal intensity compaed with baseline fo scenes (and duing low intention encoding of paintings compaed with baseline in the ight PPA) but not fo faces, wheeas the FFA exhibited above-baseline esponse fo all stimuli. PPA activity has mostly been epoted fo scenes o houses, with weake but eliable esponse fo objects [Epstein, 2005]. The fact that PPA esponse to abstact paintings was lowe than its esponse to scenes is inteesting, as it suppots the hypothesis, poposed by Epstein and Kanwishe [1998], that the PPA pocesses infomation about the geometic layout of local space. Although the abstact paintings ae as complex and inteesting as the scenes and cove the same section of the visual field, they do not depict ealistic thee-dimensional envionments and thus would be pedicted by the spatial layout hypothesis to engage the PPA less stongly than the scenes, as we obseved. The FFA, in line with pevious findings [Gauthie et al., 1999; Ta and Gauthie, 2000; Tong et al., 2000; Xu, 2005] while esponding most stongly to faces, also esponded moe to othe nonface stimuli than to the blank-sceen baseline. FFA and PPA activity was also modulated by intentional task instuctions, suggesting that activity in these aeas can eflect both the executive demands of a condition as well as the stimulus chaacteistics. Howeve, in contast to pattens of activity in the mid-vlpfc, it was not the case that all high intention conditions elicited moe activity than low intention conditions. As discussed, FFA and PPA activity was only modulated by intention, if stimuli the 116

11 Engagement of VLPFC in Intentional Pocesses stimuli wee of a type favoed by that egion. In the PPA, this modulation was only obseved fo scenes. The FFA, which was activated by all stimuli duing the passive condition elative to baseline, showed inceased activity in the high-intention conditions fo all stimulus categoies. Seveal studies in the memoy liteatue suggest that PPA and FFA activity may be modulated by executive demands of the task [Duzgal and D Esposito, 2003; Jha et al., 2004; Ranganath et al., 2004]. Fo instance, Ranganath and othes [Ranganath et al., 2004] showed that FFA and PPA exhibited geate encoding-elated activity when thei pefeed stimulus was elevant to the ecognition task. Othe studies have demonstated inceased FFA and PPA activity when attention is diected towads thei pefeed stimuli [Vuilleumie et al., 2001; Wojciulik et al., 1998]. Taken togethe these findings suggest that, simila to findings in the mid-vlpfc, activity in posteio egions such as the FFA and PPA can be modulated by contol pocesses equied in diffeent cognitive domains, athe than by specific attentional o mnemonic pocesses. Both FFA and PPA showed less activity when stimuli whee shown duing ecognition compaed with encoding (main effect of task ). These findings could be explained by stimulus epetition effects. Such effects have been obseved in the PPA [Epstein et al., 1999, 2005; Menon et al., 2000] and the FFA [Ege et al., 2004; Ishai et al., 2004; Soon et al., 2003; Vuilleumie et al., 2003], although the opposite finding has also been obseved [Henson, 2003]. Inteestingly, these epetition effects wee specific to scenes in the PPA, but wee not specific to faces in the FFA. The specificity of the epetition effect in the PPA contasts with an ealie study by Avidan and colleagues [Avidan et al., 2002], in which epetition eductions wee found fo both houses and faces in this egion. Diffeences between the expeimental paadigms may explain these discepant esults; fo example, the ealie study measued signal eductions caused by pesentation of a stimulus twelve times within a block, while hee we measued signal eductions caused by pesentation of a stimulus twice in diffeent tials sepaated by intevening items. In the cuent study the FFA and PPA wee localized using a 1-back task. This could have led to the selection of egions within the FFA and PPA involved in memoy as well as peceptual pocesses - although thee ae othe findings which suggest that the 1-back technique poduces simila esults to passive viewing [Kanwishe et al., 2001]. CONCLUSION The mid-vlpfc was diffeentially activated unde conditions duing which voluntees wee asked to have a paticula intention towads the stimuli. This esult is consistent with the idea that cetain aeas within the pefontal cotex ae involved in contol pocesses, i.e. pocesses that enable us to cay out actions intentionally, with delibeate conscious contol [Duncan and Owen, 2000; Noman and Shallice, 1986]. Novel aspects of ou appoach include the testing of specific hypotheses about a specific aea within the mid- VLPFC [Duncan and Owen, 2000], instead of focusing on the pefontal cotex o VLPFC as a whole, as in many pevious studies. Futhemoe we aimed to diffeentiate pattens of activity in the mid-vlpfc and in highe visual aeas. The esults showed that not only the mid-vlpfc, but in fact all investigated aeas wee diffeentially activated unde conditions duing which voluntees wee asked to have an intention towads the stimulus. Thus all aeas wee sometimes involved in o at least activated by intentional instuctions- o, moe boadly speaking, some contol pocess. The esults ae cetainly consistent with the idea of modulation of activity in posteio aeas by the mid-vlpfc [Petides, 1994] although othe outes leading to coactivation ae possible. Anothe finding is consistent with this idea: FFA and PPA activity was only modulated in conditions equiing intentional contol, if stimuli wee pesented that elicited activity in these egions duing passive viewing compaed with baseline. Pehaps intentional pocessing leads to a modulation of activity in those posteio egions that pocess a stimulus duing passive viewing. Futhemoe the esults suggest that the mid-vlpfc was the aea that was the least influenced by the actual stimuli and most clealy influenced by the task goal o by what was intended to be done with the stimulus. In fact, just pesenting stimuli unde passive viewing conditions, in the absence of a paticula intention what to do with them, elicited as much activity as looking at a blank sceen fo the same amount of time. In contast to the mid- VLPFC, FFA, and PPA wee active duing passive viewing conditions compaed with baseline, if the stimulus was the ight kind fo that aea. ACKNOWLEDGMENTS The authos thank the staff at the Cente fo Functional Magnetic Resonance Imaging of the Bain (FMRIB), Oxfod, UK, fo thei assistance with the pesent study. We thank all the voluntees who took pat. We thank Matthew Bett fo assistance with the data analysis and Tom Nielsen and Rhodi Cusack fo pogamming the task. We thank Simon Lewis fo helpful discussions on this wok. REFERENCES Avidan G, Hasson U, Hendle T, Zohay E, Malach R (2002): Analysis of neual selectivity undelying low fmri signals. Cu Biol 12: Baddeley A, Della Sala S (1996): Woking memoy and executive contol. Philos Tans R Soc Lond B 351:

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