᭜HumanBrainMapping12:131–143(2001)᭜ Error-RelatedBrainActivationduringa Go/NoGoResponseInhibitionTask V.Menon,1,3* N.E.Adleman,1 C.D.White,1 G.H.Glover,2 andA.L.Reiss1,3 1DepartmentofPsychiatryandBehavioralSciences,StanfordUniversitySchoolofMedicine, Stanford,California 2DepartmentofRadiology,StanfordUniversitySchoolofMedicine,Stanford,California 3PrograminNeuroscience,StanfordUniversitySchoolofMedicine,Stanford,California ᭜ ᭜ Abstract:Inhibitorycontrolandperformancemonitoringarecriticalexecutivefunctionsofthehuman brain.Lesionandimagingstudieshaveshownthattheinferiorfrontalcortexplaysanimportantrolein inhibitionofinappropriateresponse.Incontrast,specificbrainareasinvolvedinerrorprocessingand theirrelationtothoseimplicatedininhibitorycontrolprocessesareunknown.Inthisstudy,weuseda randomeffectsmodeltoinvestigateerror-relatedbrainactivityassociatedwithfailuretoinhibitresponse duringaGo/NoGotask.Error-relatedbrainactivationwasobservedintherostralaspectoftheright anteriorcingulate(BA24/32)andadjoiningmedialprefrontalcortex,theleftandrightinsularcortexand adjoiningfrontaloperculum(BA47)andleftprecuneus/posteriorcingulate(BA7/31/29).Brainactiva- tionrelatedtoresponseinhibitionandcompetitionwasobservedbilaterallyinthedorsolateralprefrontal cortex(BA9/46),parstriangularisregionoftheinferiorfrontalcortex(BA45/47),premotorcortex(BA 6),inferiorparietallobule(BA39),lingualgyrusandthecaudate,aswellasintherightdorsalanterior cingulatecortex(BA24).Thesefindingsprovideevidenceforadistributederrorprocessingsysteminthe humanbrainthatoverlapspartially,butnotcompletely,withbrainregionsinvolvedinresponse inhibitionandcompetition.Inparticular,therostalanteriorcingulateandposteriorcingulate/precuneus aswellastheleftandrightanteriorinsularcortexwereactivatedonlyduringerrorprocessing,butnot duringresponsecompetition,inhibition,selection,orexecution.Ourresultsalsosuggestthatthebrain regionsinvolvedintheerrorprocessingsystemoverlapwithbrainareasimplicatedintheformulation andexecutionofarticulatoryplans.Hum.BrainMapping12:131–143,2001. ©2001Wiley-Liss,Inc. Keywords:prefrontalcortex;cingulatecortex;fMRI;inhibition;Go/NoGo ᭜ ᭜ INTRODUCTION Cognitivetheoriesofthehumanbrainpositthat executivetaskcontrolandperformancemonitoring arecriticalfunctionsoftheprefrontalcortex(PFC) Contractgrantsponsor:NIH;Grantnumbers:MH50047,MH01142, [Logan,1985;Luria,1966].Animportant,butlesswell andHD31715.Grantsponsor:TheM.I.N.D.Institute. studied,aspectofprefrontalcortexfunctionisperfor- *Correspondenceto:V.Menon,Ph.D,DepartmentofPsychiatryand BehavioralSciences,401QuarryRoad,StanfordUniversitySchool mancemonitoring,whichincludeserrordetectionand ofMedicine,Stanford,CA94305-5717.E-mail:[email protected] errorcorrectiontoenableimprovedtaskaccuracy Receivedforpublication28April2000;accepted10October2000 [Reason,1990].Anumberofindirectfindingssuggest ©2001Wiley-Liss,Inc. ᭜ Menon et al. ᭜ that humans can monitor actions and detect and com- Gemba, 1986] and cognitive [Jonides et al., 1998] pro- pensate for errors [Rabbitt 1966a, 1966b]. For example, cesses. These and other similar findings have led to the subjects tend to slow down on trials subsequent to proposal that inhibitory control is a central function of errors [Rabbitt, 1966b]. The strongest evidence for the the PFC [Fuster, 1997; Roberts et al., 1998]. Based on existence of a neural system that implements error primate lesion studies, it was originally hypothesized processing has come from the recent discovery of a that inhibitory control was a function localized to the component of event-related potentials (ERPs). These ventral (orbitofrontal) PFC [Fuster, 1997; Rolls, 1996]. studies have shown that when subjects make an error, However, more recent lesion, neurophysiological, and an error-related negativity (ERN) occurs 100 msec af- brain imaging studies have implicated other regions of ter response onset. The ERN is maximal at fronto- the PFC, including the dorsolateral prefrontal cortex central recording sites on the human scalp with a peak (DLPFC) [Shimamura, 1995; Dias et al., 1997], the in- voltage of up to 10uV [Gehring et al., 1993; Falkenstein ferior frontal cortex [Konishi et al., 1998; Garavan et et al., 1995a]. al., 1999] and the AC cortex [Taylor et al., 1997; Posner, Brain areas that contribute to error processing, par- 1998] in response inhibition. The role of these regions ticularly in relation to executive functions such as in error processing, if any, is poorly understood. inhibitory control, remain poorly understood. Based The Go/NoGo task provides a simple paradigm on dipole modeling of the ERP, the anterior cingulate with which to investigate brain activation during op- (AC) has been considered a putative source of the erations such as error processing, as well as response ERN [Dehaene et al., 1994]. However, given the inher- inhibition and response competition. ERP studies ent indeterminacy of dipole source localization, dipole have shown the presence of distinct components re- sources cannot be used to make conclusive inferences lated to response inhibition and error-related signals about neural generators of the ERN [Miltner et al., during the Go/NoGo [Roberts et al., 1994; Falkenstein 1997]. Two recent functional magnetic resonance im- et al., 1995b; Kiefer et al., 1998]. We used a Go/NoGo aging (fMRI) studies of error processing have been task in an fMRI study to investigate brain regions conducted using different paradigms. Carter et al. involved in error processing following failure to in- [1998] used a continuous performance task (AX-CPT) hibit response. Previous imaging studies of the Go/ and they reported that the dorsal AC was activated NoGo task have focused exclusively on response in- during error processing as well as during tasks with hibition and competition. Konishi et al. [1998] used an increased response competition. In exploratory analy- event-related design with equiprobable Go and NoGo sis they also reported that the left and right dorsolat- events and found activation in the right inferior fron- eral prefrontal cortex were activated during error pro- tal sulcus during correctly inhibited NoGo events. cessing but not during response competition. Kiehl et However, this study only used five subjects, sampled al. [2000] used a Go/NoGo paradigm that is more a limited area of the PFC, and did not involve the closely related to electrophysiological studies of the establishment of a prepotent response that the subjects ERN. They reported that the anterior rostral but not had to inhibit. Two recent developmental fMRI stud- the dorsal AC, and the left but not the right dorsolat- ies of the Go/NoGo used a paradigm that involved eral prefrontal cortex were involved in error process- buildup of a significant level of prepotent response, ing. Thus, the precise role of the AC in error process- and reported diffuse activation of the PFC [Casey et ing and response inhibition is not known, and it is not al., 1997; Vaidya et al., 1998]. Limitations of these clear whether the AC makes a unique contribution to studies include the use of prespecified ROIs and the error processing. Furthermore, the contribution of restricted brain area evaluated, often not including the other brain areas, if any, to error processing is un- entire PFC. Using an event-related fMRI design, Ga- known. ravan et al. [1999] found greater activation in the PFC, Inhibitory control mechanisms are a critical compo- as well as the inferior parietal lobe, during response nent of the response selection processes that contrib- inhibition. To our knowledge, only one study has ute to accurate performance [Roberts et al., 1998] and examined whole-brain event-related activity during as such may or may not be related to error processing. error processing [Kiehl et al., 2000], and only one Lesion and imaging studies have shown that the PFC study has examined whole-brain activation during re- plays a critical role in inhibition of perseverative be- sponse inhibition [Garavan et al., 1999]. havior [Iversen and Mishkin, 1970], inhibition of dis- The aims of our study were twofold: first, investi- tracting sensory information [Chao and Knight, 1998], gate which brain areas are involved in error process- and inhibition of inappropriate prepotent response ing over and above response inhibition and competi- tendencies in motor [Konishi et al., 1998; Sasaki and tion; and second, determine the extent to which this ᭜ 132 ᭜ ᭜ Brain Activation During Error Processing ᭜ network overlaps with brain regions underlying re- thus requiring response to half the trials (Go trials) sponse inhibition and competition on the one hand, and response inhibition to the other half (NoGo trials). and motor response execution on the other. We used a At the beginning of each epoch, a 2-sec instruction standard blocked design [Casey et al., 1997] in this warned the subject about the new task condition. study as a way to provide and maintain a high level of prepotent response. Randomly presenting an equal fMRI acquisition number of Go and NoGo stimuli would have elimi- nated buildup of a prepotent response. Further, alter- Images were acquired on a 1.5T GE Signa scanner ing the proportion of Go and NoGo stimuli would with Echospeed gradients using a custom-built whole have invoked processes unrelated to either response head coil that provides a 50% advantage in signal to inhibition or error processing [Menon et al., 1997; Milt- noise ratio over that of the standard GE coil [Hayes ner et al., 1997; Posner, 1998]. Weighted mean images and Mathias, 1996]. A custom-built head