Effects of Anterior Cingulate Fissurization on Cognitive Control During Stroop Interference

Transcription

1 Human Bain Mapping 30: (2009) Effects of Anteio Cingulate Fissuization on Cognitive Contol Duing Stoop Intefeence Rene J. Huste, 1,2,3 * Casten Woltes, 2 Andeas Wollbink, 2 Elisabeth Schweige, 1 Wene Wittling, 1 Chisto Pantev, 2 and Makus Junghofe 2 1 Cente fo Neuopsychological Reseach, Univesity of Tie, Tie, Gemany 2 Institute fo Biomagnetism and Biosignalanalysis, Univesity of Münste, Münste, Gemany 3 Depatment of Psychiaty and Psychotheapy and Intedisciplinay Cente fo Clinical Reseach (IZKF), Univesity of Münste, Münste, Gemany Abstact: The midcingulate cotex, as pat of the moe anteioly located cingulate egions, is thought to play a majo ole in cognitive pocesses like conflict monitoing o esponse selection. Regading midcingulate fissuization, the occuence of a second o paacingulate sulcus is moe common in the left than in the ight hemisphee and has been shown to be associated with an advantageous pefomance on tests of executive functions. Howeve, the cognitive mechanisms undelying such behavioal diffeences ae completely unknown. The cuent study addessed this issue by compaing subjects with a low and a high degee of left hemispheic midcingulate fissuization while collecting behavioal as well as electophysiological coelates of Stoop intefeence. A high degee of fissuization was associated with deceased behavioal Stoop intefeence accompanied by a stonge and polonged fontal negative potential to inconguent tials stating aound 320 ms. This inceased fontal negativity is assumed to eflect an enhanced activity of a conflict monitoing system located in the midcingulate cotex. In contast and stating aound 400 ms, subjects with low fissuization evealed an inceased positivity ove paieto-occipital egions suggesting a compensatoy need fo enhanced effotful cognitive contol in this goup. These esults contibute to the undestanding of the neuonal implementation of individual diffeences egading attentional mechanisms. Hum Bain Mapp 30: , VC 2008 Wiley-Liss, Inc. Key wods: dacc; stoop; paacingulate; conflict monitoing; cognitive contol; fissuization INTRODUCTION As the most pominent stuctue of the human medial wall, the cingulate cotex has been subject to emakable investigation egading its contibution to cognitive pocesses. As it tuned out, especially dosal anteio potions of the cingulate cotex seem to be elated to pocesses such *Coespondence to: R.J. Huste, Institute fo Biomagnetism and Biosignalanalysis, Malmedyweg 15, Münste, Gemany. huste@uni-muenste.de Received fo publication 15 Octobe 2007; Revised 13 Mach 2008; Accepted 21 Mach 2008 DOI: /hbm Published online 20 June 2008 in Wiley InteScience (www. intescience.wiley.com). as cognitive contol [Fan et al., 2003], conflict monitoing [Botvinick et al., 2004b], esponse selection [van Veen and Cate, 2005], eo pocessing [Mathalon et al., 2003] o ewad based decision making [Bush et al., 2002]. Paticulaly, the conflict monitoing view and its computational implementation by Cohen and colleagues [see Bogacz et al., 2006; Cohen et al., 2004] offe a poweful tool to the undestanding of anteio cingulate functioning. Although the cingulate cotex seems to be a unitay stuctue at fist sight, ecent eseach shows a high degee of functional as well as stuctual vaiability [Devinsky et al., 1995; Huste et al., 2007; Paus et al., 1996a; Vogt et al., 1992, 1995, 2003; Yucel et al., 2001]. With espect to the anteioly located cingulate egions, a functional distinction between an affective and a cognitive subdivision has been put fowad [e.g. Bush et al., 2000] with the latte VC 2008 Wiley-Liss, Inc.

2 Huste et al. Figue 1. Midcingulate cotex and its suface topogaphy. (a) This figue schematically depicts the suface mophology of the human medial wall. Accentuated in light gay is the midcingulate cotex (MCC), situated ight above the copus callosum (dak gay). (b) These sagittal and coonal views of a subject show a gyal doubling in the left- (occuence of cingulate and paacingulate gyi) and a single cingulate gyus only in the ight-hemispheic midcingulate egion. being stongly associated with those pocesses descibed above. This specific aea anatomically likely coesponds to the midcingulate cotex (MCC; see Fig. 1a fo a depiction) as descibed by the fou-egion model of Vogt et al. [2003] and is also often efeed to as the dosal anteio cingulate cotex (o dacc). In Vogt s model, the MCC is diffeentiated fom the anteio cingulate cotex (ACC, fomely also denominated peigenual ACC o pacc). This division of the cingulate cotex, on the contay, seems to match the affective subegion o vental ACC (vacc). One vey appaent patten egading egional mophological vaiability is the doubling of gyi and sulci fequently found in the MCC and the (peigenual) ACC. In these cases, the supeio gyus/sulcus is usually temed the paacingulate gyus/sulcus (PCG/PCS), wheeas the infeio elements ae efeed to as cingulate gyus/sulcus (CG/CS). Please efe to Figue 1 (panels a and b) fo an illustation. The fist quantitative evaluation egading vaiations in anteio cingulate folding was done by Paus et al. [1996a]. By manually tacing the PCS in the midcingulate egion, the degee of egional fissuization was opeationalized. In a lage sample of 247 subjects, they found hemispheic diffeences in PCS occuence and extension, as the PCS was moe often pesent and moe extended in the left as compaed to the ight hemisphee. In a study of Yucel et al. [2001], a leftwad hemispheic asymmety was futhe cooboated by computing individual asymmety metics showing a highe degee of asymmety in ight-handed males as compaed to ighthanded female subjects. This gende diffeence in ighthanded subjects has ecently been confimed [Huste et al., 2007], but a evesal was found in left handes, theeby indicating an inteaction of gende and handedness. Howeve, the leftwad asymmetic patten in MCC folding was dominating in all goups. Sepaate analyses pe hemisphee additionally indicated that these vaiations in asymmety ae likely diven by the left athe than the ight hemisphee. Theoetical accounts suggest that the degee of egional fissuization may be associated with vaiations in local cytoachitectue and neual connectivity [see Too and Bunod, 2005 fo a thoough discussion]. In accodance with this notion, inteindividual diffeences in midcingulate fissuization wee shown to be coelated with vaieties concening othe neuoanatomical attibutes of this egion. Fo example, the pesence of a PCS seems to be indicative of a elative expansion of cytoachitectual aea 32 0 [Vogt et al., 1995]. Similaly, Paus et al. [1996b] found a negative association of the intasulcal gay matte volumes of the PCS and the CS. In moe ecent studies, Fonito et al. found the occuence of a PCS to affect the oveall volume and those of cingulate subegions (2004; 2008). Moeove, subjects with a leftwad PCS asymmety seem to exhibit a distinct pofile of bilateal changes in cotical thickness [Fonito et al., 2007]. Tuning back to the functional chaacteistics of the MCC, most of the data obtained in neuoimaging and event-elated potential (ERP) studies seem to be explainable by viewing this egion as a conflict monitoing system [see, fo example, van Veen and Cate, 2002a]. It is boadly accepted that the MCC is specifically esponsive to the occuence of conflict in elevant pocessing pathways. This egion then signals the need fo an incease in attentional contol, likely exeted by pefontal cotical aeas. It is not supising, theefoe, that the so called intefeence tasks consistently lead to activations in the MCC. A well-known example fo this kind of task is given by the Stoop paadigm [e.g. Pado et al., 1990]. In a metaanalytic evaluation of Stoop fmri data [Laid et al., 2005], two diffeing methodological appoaches yielded simila pattens of activation pedominantly in the infeio fontal gyus and the MCC associated with the pocessing of intefeence. Notably, these data indicate the focus of midcingulate activations to be in the paacingulate egion. Taken togethe, diffeences in behavioal pefomance on tasks tapping executive contol o conflict monitoing pocesses ae to be expected with subjects exhibiting diffeences with espect to asymmeties of midcingulate fissuization. This assumption is based on the association of mophological diffeences in MCC fissuization with undelying neuoanatomical chaacteistics on one hand 1280

3 Effects of Anteio Cingulate Fissuization and the cited findings fom the functional neuoimaging liteatue on the othe hand. Thee aleady is some indication fo the appopiateness of this assumption. Fonito et al. [2004, 2007] contasted goups with vaying degees of PCS asymmety in solely behavioal tasks engaging executive cognitive pocesses and contol conditions. Hee, subjects showing a leftwad asymmetic patten of MCC folding did bette in vebal as well as nonvebal executive tasks when compaed to subjects with ightwad asymmetic o symmetic midcingulate fissuization. Howeve, the cognitive mechanisms diving such behavioal diffeences need futhe investigation. One aim of the pesent study was to gathe futhe evidence fo an association of egional midcingulate fissuization and behavioal pefomance in an intefeence task. A vesion of the Stoop paadigm [MacLeod, 2005] was chosen fo this pupose as the intoduced intefeence effect appeas to be highly obust. Specifically, when subjects ae asked to indicate the colo of a wod, a elative incease in eaction times to inconguent stimuli (wod meaning and font-colo do not match) as compaed to conguent ones (both stimulus dimensions give analog infomation) can eliably be seen. Secondly, to elucidate the tempoal dynamics and inteactions of cognitive pocesses tapped by the task at hand that might undelie such expected behavioual diffeences between fissuizational goups, ERPs wee ecoded fo late spatio-tempoal analysis. Pio ERP studies eliably found two Stoop-elated effects in the stimulus-locked bain activity indicating diffeences in the pocessing of conguent and inconguent tials [Liotti et al., 2000; Makela-Leenc et al., 2004; van Veen and Cate, 2002b; West, 2003]. Fist, moe negative going waves can be seen at fonto-cental electodes between 300 and 500 ms fo inconguent stimuli. This elative negative deflection has been shown to have a main neuonal geneato situated in the MCC [Liotti et al., 2000; Makela- Leenc et al., 2004; West, 2003] and is thought to eflect the detection of conflict. Late on in time, a highe positivity in the inconguent as compaed to the conguent condition develops ove posteio aeas. In spite of some ageement that this late elative positivity stems fom an incease in cognitive contol eflecting the adaptation to task demands, the exact sites and souces fo this effect ae still a matte of debate. Based on these findings and in addition to the behavioal expectations, we assumed diffeences in the pocessing of conflict between subjects showing a high degee as opposed to those with a lowe degee of MCC fissuization to occu pedominantly between 300 and 500 ms egading measued ERPs. MATERIALS AND METHODS Subjects A total of 16 subjects (8 females) paticipated in the study as outlined below. These subjects wee ecuited accoding to thei MCC mophology afte sceening of 90 individual anatomical T1-weighted MRI scans ( mm) fom the institutes subject pool (Institute fo Biomagnetism and Biosignalanalysis, Univesity of Münste, Gemany). Only ight handes wee included and the Edinbugh Handedness Inventoy [Oldfield, 1971] was used to psychometically validate nominal hand pefeence. None of the subjects epoted a histoy of psychiatic o neuological disodes. Due to stongly deviating signal to noise atio in the ERP data, one female subject had to be excluded fom futhe analysis. Thus, the final sample consisted of 15 subjects with a high (HF; male 5 4, female 5 3) and a low (LF; male 5 4, female 5 4) degee of fissuization of the MCC. The paticipants age anged fom 22 to 39 (mean yeas) and HF/LF goups wee matched fo age and education. All subjects had completed high school education with a minimum of 10 yeas of schooling. Paticipants wee tested fo nomal visual acuity as well as colo vision. Witten infomed consent was obtained pio to study paticipation. MCC Classification Potocol In accodance with pevious studies [Huste et al., 2007; Paus et al., 1996a; Yucel et al., 2001] the degee of individual MCC fissuization was quantified by measuing the occuence and extension of the PCS. The appoach taken hee is based on a pio study and poofed to achieve high coefficients with espect to both inte- and inta-ate eliability [fo a detailed desciption see Huste et al., 2007]. The MCC was specified fo each of the 90 individuals within the subject pool on the elevant anatomical T1- weighted image. Wheeas the ostal bode was defined by a line at the most anteio extension of the callosal genu, the posteio delineation was given by a line unning 10 mm caudally to the anteio commissue; both lines wee pojected pependicula onto the AC-PC plane. The PCS was defined as a fissue unning dosal and paallel to the CS. It had to be visible on the midsagittal plane and on at least thee moe lateal slices. If pesent, the extension of the PCS was taced voxelwise to yield a esolution in millimetes. Inteuptions o gaps in the sulcal couse wee disegaded. These continuous measuements wee tansfomed to a categoical vaiable fo each hemisphee by gouping them in steps of 15 mm. Accoding to this pocedue, individual scoes pe hemisphee egading the PCS occuence ae epesented in five categoies anging fom 0 (absent; no evidence fo a gyal doubling o a supposed PCS shows a length of less than 15 mm) to 4 (pominent; moe than 60 mm length of an estimated PCS). In this study, subjects fom the LF goup did not show a PCS in eithe hemisphee (categoy 0). To be included in the HF goup the paticipants PCS had to be pominent (categoy 4) in the left but completely absent (categoy 0) in the ight hemisphee. By aanging these goups, subjects with an exteme fom of the most common leftwad asymmetic patten of MCC fissuization [Huste et al., 2007; Yucel et al., 2001] wee compaed to 1281

4 Huste et al. the less common case of symmety without a PCS in eithe hemisphee. Although planned, a ightwad asymmetic goup matched to the HF goup egading the degee of folding explicitness could not be deived fom the subject pool. Stimuli and Pocedue A andomly mixed-tial vesion of the Stoop task was used. Subjects wee instucted to indicate the font-colo in which the colo-wods ed, blue, geen o yellow wee pesented by manually esponding with the left o ight index finge. The font-colos blue and geen wee assigned to one, wheeas ed and yellow wee matched to the othe index finge. The specific font-colo to finge mapping was balanced acoss gende and fissuizational goups. With stimuli of the conguent condition, font-colo and colowod wee identical (e.g. blue witten in blue). In case of the inconguent condition stimuli wee not only semantically at conflict but the colo of font and wod also pointed to diffeent esponse finges (e.g. blue pinted in ed). The inconguent condition employed in ou study was based on the diffeentiation of semantic and esponse conflict as descibed by van Veen and Cate [2005]. Accoding to thei obsevations, a highe difficulty, and theefoe a maximal effect, can be achieved by combining conflict at both the semantic and the esponse level. The expeimental task began with an acquisition phase to familiaize the subjects with the elevant esponse assignments. Hence, subjects wee pesented with 16 tials duing which coloed boxes wee shown and the coect esponse had to be made. Feedback, whethe the esponse was accuate, was given immediately afte the button pess. Then, anothe block of 16 taining tials encompassing the genuine Stoop stimuli was pesented, again with feedback afte each sepaate tial. This time, feedback was also given when the esponse was too slow (eaction time >1,350 ms). The actual expeimental phase consisted of six blocks with 64 tials each (50% conguent and 50% inconguent). The paticipants wee instucted not to emphasize speed ove accuacy o vice vesa. A blockwise feedback was shown on the sceen. Subjects wee encouaged to poceed as in the peceding block as long as thei aveage eaction time was faste than 700 ms and the eo ate was below 10%. Othewise, subjects wee instucted to speed up esponding and/o to eact moe accuately, espectively. At the beginning of a tial a fixation coss was shown with a andomized duation of ms, followed by a taget pesentation of 500 ms. A tial teminated afte anothe 950 1,350 ms, meanwhile displaying a fixation coss. Tials wee sepaated by a vaiable intetial inteval of 800 1,200 ms duing which a blank sceen was pesented. Stimuli wee pojected onto a sceen in a dimly lit oom via a beame system while the exact physical taget onset was measued by a photo diode. The Pesentation softwae package (Pesentation 9.90, Neuobehavioal Systems, Albany; USA) was used to opeate the expeimental pocedue and to ecod behavioal esponses. Stimuli wee displayed against a black backgound in the cente of the sceen with a distance of 60 cm and an aveage visual angle of ERP Acquisition and Paameteization Electophysiological as well as neuomagnetic esponses wee ecoded in a magnetically shielded oom, using a CTF Omega system fo concuent measuements of EEG and MEG (VSM MedTech, Coquitlam, Canada). As the integation of infomation fom both the EEG and the MEG modality fo individual neual souce analyses is still in pogess, the emainde of this aticle will exclusively focus on ERP data. Electophysiological indices of bain activity wee ecoded fom 63 sinteed Ag/AgCl electodes mounted on a flexible lyca-electocap (easycap, Falk Minow Sevices, Munich, Gemany) accoding to the system fo electode placement [Chatian et al., 1985]. The vetical and hoizontal electooculogams (EOG) wee ecoded fom fou electodes placed on the oute canthi of both eyes and fom the infa- and supa-obital idges of the ight eye. EEG and EOG ecodings wee taken continuously fom DC up to 200 Hz, at a sampling ate of 600 Hz. Impedances wee kept below 5 kx and matched fo homologous sites with a maximum deviation of 500 X. Cz was used as online efeence and a gound electode was placed on the foehead. Offline, all electodes wee eefeenced against the common aveage efeence and filteed fom 0.1 to 15 Hz to incease the signal-to-noise atio. Ocula (blinks and eye movements), muscula, as well as technical, atefacts wee ejected offline by visual inspection. The continuous EEG was then segmented into epochs fom 200 ms pestimulus to 800 ms poststimulus and baseline coected to the mean of the pestimulus inteval. Aveages wee computed sepaately fo both the conguent and inconguent conditions excluding tials with eoneous esponding as well as posteo tials. Offline pocessing of the EEG data was done using the Bain Electical Souce Analysis pogam (BESA, Vesion 5.1.7, Megis Softwae, Heidelbeg, Gemany) and the ElectoMagnetic EncaphaloGaphy Softwae (EMEGS, Vesion 2.1). Statistical Analyses A epeated-measue Analysis of Vaiance (ANOVA) with goup (LF/HF) and condition (Conguent/Inconguent) was computed to assess the behavioal effects egading mean eaction times on tials with coect esponding, also excluding post-eo tials. Regading the accuacy data, Mann Whitney U tests wee calculated fo both conditions to assess diffeences between HF and LF subjects. In addition, a sepaate 1282

5 Effects of Anteio Cingulate Fissuization Wilcoxon-test fo each goup was used to test fo diffeential accuacy between conditions. The so called posteo slowing, an incease in eaction times to stimuli following an eo tial, which is believed to eflect an adaptation in cognitive contol, was evaluated, too. To this end, an ANOVA was computed with goup as between facto and compaing eaction times fom coect esponses not peceded by an eo and esponses following tials with eoneous pefomance. The actual tials enteing the analysis wee conguent only as to avoid confounding with goup-specific diffeences in the pocessing of conflict. Afte visual inspection of the ERPs and in accodance with pio findings fom the liteatue, aithmetic means of the voltage amplitudes fom the following time intevals wee computed: ms, ms and ms. ERP data fo these effects wee analyzed by two sepaate epeated-measues ANOVAs fo each time window. The fist analysis included the topogaphic facto midline with Fz, Cz and Pz as electode locations. This appoach eflects the standad way of analyzing the effects of inteest as the condition-specific diffeentiations in the Stoop paadigm seem to be most ponounced ove the hemispheic midline. Nevetheless, given the exploatoy natue of this analysis, a second ANOVA was conducted to moe thooughly assess topogaphic effects. Hemisphee (left/ ight), egion (anteio/cental/posteio) and eccenticity (inne/oute adius; F3 F4, C3 C4, P3 P4 vs. F7 F8, T7 T8, P7 P8) wee used to descibe ERP scalp amplitude distibutions moe specifically. Both ANOVAs included goup (LF/HF) and condition (Conguent/Inconguent) as futhe factos of inteest. Lowe-ode effects ae epoted only if the natue of highe-ode inteactions allow fo thei intepetation. Geenhouse Geisse epsilon coections wee computed when appopiate. The softwae package SPSS (SPSS, Chicago, USA) was used fo statistical evaluations. Fishe LSD tests wee calculated fo post-hoc assessments of elevant statistics but will explicitly be mentioned only when of special inteest fo the intepetation. In addition to statistical significance testing, effect size estimates wee computed using the pocedues descibed in Rosenthal [1994] and Kline [2004]. Hee, 2 and x 2 wee computed fo nonpaametic and paametic statistical compaisons, espectively. These measues ae an estimate fo the explained vaiance and ange fom zeo to one. Fo vaiance-analytic pocedues, x 2 is compaable to R 2 with both measues indicating the popotion of the vaiance that is attibutable to the effect. Howeve, R 2 [also called estimated h 2 ; see Kline, 2004] descibes the amount of vaiance accounted fo in the sample, wheeas x 2 is an estimate of the amount of vaiance accounted fo in the population theefoe, x 2 tends to be lowe than R 2. This appoach was chosen due to the exploatoy natue of this study. Futhemoe, the sample size was constained due to the limited availability of suited subjects, which may lessen the powe of the statistical analyses. Because of the high numbe of statistical tests, effect size estimates o the degee of systematic vaiance will be epoted only in addition to elevant test statistics o when othewise of impotance fo the intepetation of obsevations. RESULTS Behavioal Data The analysis on eaction times appoved the existence of behavioal Stoop intefeence. A significant main effect of condition evealed substantially deceleated esponses to inconguent as opposed to conguent tials (F (1,13) , P < 0.001, x ). Affiming ou expectations, LF subjects showed a moe ponounced Stoop intefeence when compaed to the HF goup as evealed by an inteaction of goup and condition (F (1,13) , P < 0.05, x ; mean intefeence effects: LF ms, x ; HF ms, x ). Post hoc tests indicated the souce fo this inteaction to stem fom diffeences between goups in the inconguent but not the conguent condition (with x 2 s 0.09 and <0.01, espectively). Means and standad deviations of these effects ae depicted in Figue 2a. With espect to accuacy scoes, nonpaametic tests suggested an oveall lowe pecentage of eos in the conguent as compaed to the inconguent condition (Z , P < 0.01, ). Assessing these diffeences between conditions sepaately fo both goups, the compaison eached significance fo HF subjects only (HF: Z , P < 0.03, ; LF: Z , P < 0.21, ), theeby indicating a moe ponounced effect in these subjects. Howeve, when testing fo vaieties between goups fo each condition sepaately, no statistically significant effects wee found ( 2 < 0.02 and <0.01 fo the conguent and inconguent condition, espectively). A depiction of mean accuacy scoes can be found in Figue 2b. The analysis of posteo eaction times evealed a substantial slowing when compaed to coect esponses not peceded by an eo (F (1,12) 5 5.1, P < 0.05, x ; mean posteo slowing: ms, SD ). Goups did not diffe significantly in thei degee of posteo adjustment (see Fig. 3). Inteval ms ERP Data Both ANOVAs indicated significantly moe negative going potentials to inconguent than to conguent tials. As was expected based on pio findings, this diffeentiation was most ponounced ove the fonto-cental egion (F (2,12) , P < 0.05, x ; inteaction of factos condition and midline) and at inne electodes (F (2,26) , P < 0.03, x ; thee-way inteaction of condition, egion and eccenticity). See Figue 4 fo a depiction 1283

6 Huste et al. Figue 2. Behavioal Stoop intefeence and accuacy scoes pe goup and condition. (a) Mean eaction times and standad eos (backets) of the high (HF) and low fissued (LF) goups to conguent (CO) and inconguent (IC) stimuli. Note the attenuated degee of behavioal Stoop intefeence in HF as compaed to LF subjects. (b) Mean accuacy scoes and standad eos (backets) of HF and LF subjects in the CO and IC conditions. of Stoop intefeence in fonto-cental ERPs between 320 and 600 ms. Inteval ms The statistical analyses evealed goup-specific diffeences in the pogession of the ERPs. Only the HF goup showed an ongoing diffeentiation between conguent and inconguent tials, again with a highe elative negativity in the inconguent condition (condition by goup inteaction; F (2,26) , P < 0.02, x ) and at Fz and Cz (condition by midline inteaction; F (2,26) , P < 0.05, x ; posthoc tests egading the diffeentiation of conditions eached significance fo the HF goup only). The moe detailed topogaphic analysis again showed evidence fo the symmety of this goup-specific effect at inne electodes (thee-way inteaction of condition, goup and eccenticity; F (2,26) , P < 0.04, x ) and in the fonto-cental egion (condition by egion by eccenticity inteaction; F (2,26) , P < 0.02, x ; statistically elevant in HF subjects only as indicated by post hoc compaisons). A visualization can again be found in Figue 4. Beyond this, a main effect of goup in the analysis of the hemispheic midline indicated a global offset between HF and LF subjects with moe positive going waves in the LF goup (F (1,13) , P < 0.04, x ). Inspecting the topogaphy of the diffeence wave fom HF and LF subjects, the synopsis stongly suggests a paieto-occipital oigin of this effect (see Figs. 4 and 5). Inteval ms Figue 3. Posteo slowing. Shown ae mean eaction times and standad eos (eo bas) of subjects exhibiting a high (HF) and a low (LF) degee of midcingulate fissuization. Deceleated esponses on coect posteo tials (PERR) as compaed to coect tials not peceded by an eo (CORR) define the so called posteo slowing. Fo this late time window, a condition by midline inteaction appoached significance due to a diffeentiation of ERPs between the inconguent and the conguent condition (F (2,26) , P < 0.001, x ). Hee, bain waves evoked by inconguent tials eached moe positive amplitudes with a maximum of this effect seen at Pz and an invesion at Fz. The topogaphic factos suggest the effect to be slightly moe ponounced at lateal electodes ove the left hemisphee (thee-way inteaction of condition, eccenticity and hemisphee; F (1,13) , P < 0.01, x ) and in the paietal egion (F (2,26) , P < 0.01, x ; thee-way inteaction of condition, egion and hemisphee). A depiction of this effect is given in Figue

7 Effects of Anteio Cingulate Fissuization Fonto-cental intefeence effect between 320 and 600 ms. ERPs to conguent (CO) and inconguent (IC) stimuli aggegated ove fonto-cental electodes (Cz, C1, C2, FCz, FC1, FC2). Note the moe ponounced o polonged diffeentiation seen in high fissued (HF) as compaed to low fissued (LF) subjects. The topogaphy of the diffeence wave fo the elevant time Figue 4. windows (gay) can be seen in the uppe ight cone; dak colos indicate negativity wheeas bight colos indicate positive amplitudes. Obsevable as well is a global offset between goups, with moe positive going waves fo LF as compaed to HF subjects, stating to develop at about 400 ms (efe to Fig. 5 fo the topogaphy of the diffeence wave). Again, a global offset between goups was indicated by a main effect in both analyses with moe positive going waves fo LF subjects (midline: F (1,13) , P < 0.04, x ; topogaphic: F (1,13) 5 6.3, P < 0.03, x ). The Figue 5. Topogaphy of the positive offset with LF as compaed to HF subjects. The figue depicts the topogaphy of diffeence waves fo the time windows fom 400 to 600 and 600 to 800 ms indicating a highe positivity in low (LF) as compaed to high fissued (HF) subjects. scalp topogaphy of the diffeence wave can again be seen in Figue 5. DISCUSSION The obtained esults foste the notion that diffeences in the degee of midcingulate fissuization ae of impotance egading neuocognitive functioning as captued in tasks tapping executive pocesses. Subjects with a ponounced egional doubling of gyi in the left midcingulate aea eveal a faste pocessing of intefeence-laden stimuli as compaed to subjects exhibiting a low degee of MCC fissuization. Electophysiological data suggest these goup diffeences in Stoop intefeence to eflect diffeent pedispositions egading the eliance on fast and elatively automatic vesus moe effotful and contolled attentional pocesses. Specifically, the behavioal data indicate a maked diffeence between both fissuization goups in the degee that incompatible infomation intefees with appopiate esponding accoding to task demands. Paticipants with a ponounced PCS/PCG coped bette with inconguent tials as manifested in faste esponding, although they did not show a simila tend towads a elevant gain in the conguent condition. These esults undescoe the specificity of this effect egading the pocessing of conflict within this paadigm. An augmented ability fo the pocessing of conflicts in the high fissued goup would also be in 1285

8 Huste et al. Figue 6. Intefeence effect ove posteio bain egions. ERPs to conguent (CO) and inconguent (IC) stimuli aggegated ove left- and ight-hemispheic electodes (P3, P5, P7, PO3, PO7 vs. P4, P6, P8, PO4, PO8). The topogaphy of the diffeence wave fo the elevant time window (gay) can be seen in the uppe ight cone; dak colos indicate negativity wheeas bight colos indicate positive amplitudes. accodance with the study of Fonito et al. [2004, 2007] who found a leftwad asymmetic folding of the MCC to be associated with bette pefomance acoss both vebal and nonvebal executive tasks, wheeas no effect was found in paadigms depending to a lowe degee on executive functions. In the study at hand, accuacy data as well pointed to slight diffeences between HF and LF subjects with a highe accuacy diffeentiation between conguency conditions in the HF goup. Howeve, assessing vaieties between goups fo each condition sepaately, effect size estimates did not suppot the elevance of this phenomenon. Wheeas the effect size fo the compaison of HF and LF subjects in eaction times to the inconguent condition was quite lage (x 2 > 0.09), simila contasts fo eos in the conguent and inconguent conditions explain less than 2% of vaiance. It can theefoe be concluded that the attenuated eaction time to inconguent stimuli with HF subjects does not oiginate fom an extensive shift towads less accuate esponding (aguing against diffeential speed-accuacy tade-offs between goups). Futhemoe, behavioal adaptation to conflict o eos, as measued via the degee of post-eo slowing seemed to be athe simila in both MCC fissuization goups. With espect to ERPs associated with the pocessing of conflict, both goups demonstated a dissociation of conditions with a highe elative negativity to inconguent tials between 320 and 400 ms at fonto-cental electodes. Notewothy, HF subjects exhibited a polongation of this effect that lasted until 600 ms afte stimulus pesentation. Thus, ERPs evealed the expected diffeence between HF and LF subjects in a time window fom 400 to 600 ms. The fonto-cental elative negativation to inconguent tials, often also efeed to as N400 o N450, has now eliably been found in seveal studies fom diffeent goups [e.g., Liotti et al., 2000; Makela-Leenc et al., 2004; West, 2003]. The cited suveys, applying souce econstuction techniques using equivalent cuent dipoles, confimed the MCC as one majo neuonal geneato undelying this effect. In accodance with this notion and given ou expeimental manipulation, it is easonable to assume that the obseved patten of ERPs stems fom vaying degees of midcingulate activation. One might ague that diffeences in the oientation of undelying geneatos might cause the obseved diffeences in ERP amplitudes as well. If this was a tenable explanation topogaphic diffeences between goups concening the fonto-cental negativity ae also to be expected. Impotantly, topogaphic analyses did not indicate vaieties between HF and LF paticipants egading the scalp distibutions of this elative negative potential, undescoing the assumption that neual geneatos did not vay substantially between time windows and goups. Howeve, a study combining both fmri and EEG measuements meant to diectly addess this issue is aleady on its way. Accoding to the conflict monitoing hypothesis [Botvinick et al., 2004a,b], the MCC esponds to the occuence of conflict duing infomation pocessing, theeby signaling the need fo adjustments in cognitive contol to pevent an oveall dop in task pefomance. It is hypothesized that this cognitive pocess may specifically be situated in cytoachitectual aea 32 0 as this egion has eliably been shown to be activated duing conflict laden tials [e.g. Laid et al., 2005]. Thee is some evidence 1286

9 Effects of Anteio Cingulate Fissuization indicating a stonge expansion of this aea with pesons exhibiting a ponounced paacingulate gyus as compaed to subjects showing a cingulate gyus only [Vogt et al., 1995]. In accodance with such a notion is the obsevation of Cosson et al. [1999], who found activations duing a wod geneation paadigm to be esticted to the cingulate gyus and sulcus in cases without a pope paacingulate gyus. With subjects exhibiting a paacingulate gyus the activations aely extended into the cingulate but wee meely found in the paacingulate egion. Nevetheless, the exact neuoanatomical undepinnings of behavioal and electophysiological effects in the context of fissuizational diffeences need futhe eseach. Despite these open issues, it seems easonable to conclude that the moe ponounced dissociation of ERPs to conguent and inconguent tials found between 320 and 600 ms in HF subjects indicates a diffeential and likely highe ability in conflict monitoing. Late in time, both goups exhibited moe positive going waves fo inconguent as compaed to conguent tials. This finding, most ponounced ove left posteio electodes, again fits well with effects obseved in pio ERP studies on the Stoop paadigm. Nevetheless, the exact neual geneatos as well as the cognitive pocesses eflected in this diffeentiation have not unequivocally been claified yet. West and Alain [2000] suggested this diffeence in positive slow waves to be due to an amplified pocessing of peceptual level colo infomation tiggeed by stimuli belonging to the inconguent condition. On the othe hand, Liotti et al. [2000] intepeted this effect as stemming fom a vaying degee of semantic pocessing, likely eflecting a suppession of conceptual infomation on inconguent tials. At least thee seems to be an ageement that this late diffeentiation mainly eflects an incease in cognitive contol tiggeed by conflict-laden stimuli. This intepetational ambiguity might be augmented by the obstacles associated with the intepetation of EEG scalp topogaphies. Inspecting the topogaphy of the diffeence wave fo this effect, contibutions fom paietal as well as geneatos in the occipital cotex ae to be assumed. Howeve, an involvement of fontal egions can not be uled out. Indeed, when contasting inconguent and conguent conditions in intefeence tasks, functional imaging studies commonly show activations in bain egions likely acting as souces (e.g. dosolateal pefontal cotex, DLPFC) and as sites (visual pocessing steam including extastiate-occipital egions) of attentional contol [e.g., Liu et al., 2004]. In a Stoop study using face stimuli while ecoding hemodynamic esponses, Egne and Hisch [2005] could show that mechanisms of cognitive contol ae associated with an amplified pocessing of task-elevant stimulus dimensions athe than the suppession of ielevant featues. This amplified cotical activation to stimulus featues, obseved in egions of the visual cotex, was accompanied by an augmented functional inteaction with the DLPFC. In accodance with these studies, it can be concluded that the obseved diffeentiation with moe positive going waves to inconguent tials pesumably eflects the activation of a boad netwok exeting cognitive contol. The amplified pocessing of task-elevant stimulus dimensions seems to be the functional equivalent to this phenomenon. Given the delayed onset of this effect when compaed to stimulus pesentation and mean eaction times, it seems adequate to assume that this late positivity to inconguent tials mainly eflects an adaptive pocess acoss tials, leading to enhanced taget pocessing on the following tial [Gatton et al., 1992]. Statistical compaisons also indicated the occuence of a distinct positive ERP offset in LF as compaed to HF subjects stating at about 400 ms afte stimulus pesentation. Again, the topogaphy of this effect denotes the involvement of a athe boad netwok, with emphasis ove the occipital egion becoming even moe evident fo the late time ange. The similaities in appeaance to the phenomenon descibed in the pevious paagaph ae obvious. In accodance with the peceding intepetation, this esult likely eflects an inceased need fo a sustained andintensifiedevaluationofstimuluschaacteistics.the obseved patten of esults suggest, that LF subjects can ely to a lesse extent on the conflict monitoing pocess, which is believed to take place in a elative automatic way. Theefoe, in these subjects, the signalling of intefeence at hand, associated with the occuence of inconguent stimuli, seems to opeate less effective as compaed to the HF goup. To pevent eithe an intense incease of eaction times and/o significant loss of accuacy, the pocessing of stimuli pincipally has to be biased towads the task-elevant stimulus dimension, hee fontcolo. This augmented degee of attentional contol in LF subjects is than eflected as a moe ponounced positive wave oiginating at about 400 ms ove posteio bain egions. The onset of this effect likely eflects the enhanced pocessing of the task featue of the given taget. With espect to the adaptation of cognitive contol afte situations of conflict, no electophysiological o behavioal evidence fo stong vaieties between goups was found: late positive slow waves elicited fom both conditions did not inteact with the facto goup and both goups showed a simila degee of posteo slowing. These findings foste the assumption that both goups use quite diffeing global stategies to esolve this kind of intefeence task, although thei adaptations in cognitive contol to the occuence of inconguent stimuli on a tial by tial basis seem to be athe alike. We suggest that the obseved patten of behavioal and electophysiological data eflect diffeences in the weighting of two majo attentional pocesses between HF and LF subjects. Because of an inceased ability in conflict monitoing as eflected in moe ponounced midcingulate esponding to inconguent tials, subjects with a high degee of MCC fissuization seem to esolve conflicts in infomation pocessing faste fo a tial at hand. Recent eseach suggests that phasic elease of noepinephine 1287

10 Huste et al. fom the locus coeuleus, eventually diectly tiggeed by MCC signals, may be the mediating facto [Aston-Jones and Cohen, 2005]. LF subjects on the othe hand, due to thei elatively poo conflict monitoing abilities, need to moe stongly ely on athe effotful pocesses of cognitive o attentional contol. This intepetation is based on a global offset of positive slow waves (stating at about 400 ms) ove posteio bain egions in these subjects. In accodance with functional imaging studies, this effect is pesumably caused by the activity of bain egions associated with the augmented pocessing of stimulus featues, such as colo [Egne and Hisch, 2005]. This is one of the few attempts addessing the impotant and often disegaded issue of neuoanatomical stuctuefunction associations. Although the obsevations made ae vey pomising and suggest elevance by itself, futhe eseach is needed to claify some concens tapped by this study. Fo example, one might ague that the loweed degee of behavioal intefeence, as eflected in mean eaction times with HF as compaed to LF subjects, comes at the cost of highe eo ates especially with inconguent tials. The obtained esults thus could meely eflect diffeences between goups concening a speed-accuacy tadeoff. In this context, seveal points ae woth consideing. Fist, even when accepting such an intepetation one still has to wonde why these goups should spontaneously diffe in this espect although a feedback was implemented to confine such effects. Beyond this, the tem speed-accuacy tade-off aleady eflects that this concept is puely behavioally defined and does not tell us much egading undelying cognitive pocesses and theefoe does not hampe ou intepetations. Second, as is aleady laid out in the Discussion section, effect size estimates fo behavioal goup diffeences pe condition each a elevant degee in eaction times fo the inconguent condition only. In addition, when coelating the diffeence scoes between conditions fo both eaction times and accuacy data, one would expect a speed-accuacy tade-off to be eflected in a elevant positive coelation of these indices. Howeve, the computed coelation did not foste the existence of a shift in pocessing stategies ( ). Summaizing, ou esults povide evidence fo an association of MCC fissuization on one and the neuocognitive oganization with espect to pocesses of executive contol on the othe side. Subjects displaying a well developed PCS/PCG did show a deceased Stoop intefeence effect when compaed to a goup exhibiting a low degee of egional folding. Electophysiological ecodings suggest that subjects with a high left hemispheic MCC fissuization can bette ely on fast o automatic attentional pocesses while subjects without a paacingulate gyus need to compensate fo thei weake attentional filte contast by moe contolled and effotful attentional mechanisms. 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