Effects of emotional context on impulse control

NeuroImage 63 (2012) 434–446

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Effects of emotional context on impulse control Matthew R.G. Brown a,⁎, R. Marc Lebel b, 1, Florin Dolcos a, 2, Alan H. Wilman b, Peter H. Silverstone a, Hannah Pazderka a, d, Esther Fujiwara a, T. Cameron Wild c, g, Alan M. Carroll a, Oleksandr Hodlevskyy a, Lenka Zedkova a, Lonnie Zwaigenbaum e, Angus H. Thompson f, g, Andrew J. Greenshaw a, Serdar M. Dursun a a

Dept. of Psychiatry, University of Alberta, Canada Dept. of Biomedical Engineering, University of Alberta, Canada Addiction and Mental Health Research Laboratory, University of Alberta, Canada d CASA Child, Adolescent, and Family Mental Health, Edmonton, Alberta, Canada e Dept. of Pediatrics, University of Alberta, Canada f Insitute of Health Economics, University of Alberta, Canada g School of Public Health, University of Alberta, Canada b c

a r t i c l e

i n f o

Article history: Accepted 21 June 2012 Available online 7 July 2012 Keywords: Functional magnetic resonance imaging NoGo Emotion Valence Impulse control Distractor IAPS Response inhibition

a b s t r a c t High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo–neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo–neutral Go) and aversive emotional distractor activation (aversive Go–neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub-linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance. © 2012 Elsevier Inc. All rights reserved.

Introduction The interaction of emotion and control of impulsive behavior is important for decision making in high-risk situations such as those involving drug or alcohol use or physical fighting. The Go/NoGo task (Donders, 1868) is a classic test of response inhibition—i.e. the control of impulsive

⁎ Corresponding author. E-mail address: [email protected] (M.R.G. Brown). URL: http://www.ualberta.ca/~mbrown2 (M.R.G. Brown). 1 Now at Applied Science Laboratory, GE Healthcare, Calgary, Canada. 2 Now at Dept. of Psychology, Neuroscience Program, and the Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, USA. 1053-8119/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2012.06.056

behavior. This task presents frequent Go stimuli, which require a button press response, with rare NoGo stimuli, which require inhibition of the button press. Inferior frontal gyrus (IFG) just anterior to the insula, and in particular right IFG, is known to be involved in NoGo trial performance (Aron et al., 2004b, 2007). IFG's proposed functions include the direct inhibition of automatic but undesired motor responses (see Aron et al., 2004b, 2007; Mitchell, 2011) as well as the detection of task-relevant stimuli regardless of whether a response is generated, inhibited, or simply not required (see Hampshire et al., 2010; Mitchell, 2011). IFG has also been ascribed roles in emotion processing, specifically, representation of emotional stimuli as well as modulation (including inhibition) of emotional responses (Dolcos et al., 2011; Mitchell, 2011). Dolcos et al. (2006) investigated modulation of working memory activation by emotional distractors, and Mitchell et

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

al. (2008) examined the effects of emotional distractor images on an operant choice task. Both studies implicated IFG in regulating distracting emotional responses. IFG is a candidate for mediating interaction of response inhibition and emotion. In this study, we used a modified version of the Go/NoGo task that presented task-irrelevant, emotional distractor images simultaneously with the Go/NoGo stimuli. This emotional Go/NoGo task allowed us to examine how aspects of neural processes underlying decision-making are affected by the presence of a distracting emotional context. Several previous functional magnetic resonance imaging (fMRI) studies have combined the Go/NoGo task with emotional stimuli to explore the interaction of emotion and behavioral control. Goldstein et al. (2007) used emotional word stimuli whose font (regular vs. italic) served as the Go/NoGo signal. They found evidence for interaction of emotion and behavioral inhibition in a variety of regions including IFG. Shafritz et al. (2006) compared emotional and non-emotional versions of the Go/NoGo task. Both Goldstein et al. (2007) and Shafritz et al. (2006) used block designs optimized for detection of brain regions exhibiting inhibition and/or emotion-related activation differences. These block designs precluded strong conclusions about the precise roles played by these regions because they modulated task switching and task set as well as response inhibition requirements in the different blocks. Shafritz et al. (2006) and two other fMRI studies (Hare et al., 2005, 2008) used emotional Go/NoGo stimuli whose valence served as the Go/NoGo signal. These authors focused on participants' fMRI responses to emotional stimulus valence and on decision making (response inhibition) based on emotional stimuli. Their goal was not to separate processing related to emotional distraction from behavioral inhibition processing. Previous fMRI studies have examined the modulation of taskirrelevant emotional stimulus processing by the cognitive and/or attentional demands of a competing cognitive task (Mitchell et al., 2007; Pessoa et al., 2005). Increased cognitive/attentional load tends to decrease emotion-related fMRI responses in limbic structures such as the amygdala. In the current study, we examined modulation of response inhibition activation by task-irrelevant emotional distractors. It remains an open question how brain regions supporting response inhibition, including IFG, are affected by distracting emotional stimuli that are external to the task being performed. To explore this issue, we used high field 4.7 T rapid event-related fMRI with a Go/ NoGo task that presented emotional distractor pictures (aversive vs. neutral) simultaneously with the Go/NoGo stimuli (square vs. circle). Our fMRI study is the first to combine the Go/NoGo task with emotional distractor pictures using an event-related design. This design allowed us to separate emotion- and inhibition-related activity from task switching and task set activity. Based on the Go/NoGo literature (see Aron et al., 2004b, 2007; Mitchell, 2011; Nee et al., 2007; Wager et al., 2005), we expected that IFG would exhibit inhibition-related activity—that is, greater activation for NoGo trials paired with neutral

Interference Hypothesis

435

emotional distractors (neutral NoGo trials) compared to Go trials paired with neutral distractors (neutral Go trials). We also expected IFG to show emotion-related activation in the form of a larger fMRI signal magnitude for Go trials with aversive distractor pictures (aversive Go trials) than for neutral Go trials (see Dolcos et al., 2006, 2011; Mitchell, 2011). We tested three different hypotheses on how inhibition- and emotion-related processes might interact in IFG: the interference hypothesis, the additive hypothesis, and the enhancement hypothesis (also see Fig. 1). The three hypotheses made different predictions for IFG activation evoked by NoGo trials paired with aversive distractor pictures (aversive NoGo trials). The interference hypothesis (Fig. 1 left panel) predicted that inhibition- and emotion-related processes would interfere competitively with each other. This interference would result in lower activation for aversive NoGo trials compared to neutral NoGo trials or aversive Go trials. The additive hypothesis (Fig. 1 middle panel) predicted that inhibition- and emotion-related processes would operate in parallel without affecting each other or that they would modulate each other at the neuronal level without altering each other's fMRI signal magnitudes. In either case, the additive hypothesis predicted that emotional inhibition activation (aversive NoGo–neutral Go) would be approximately the sum of inhibition activation (neutral NoGo–neutral Go) and emotion activation (aversive Go–neutral Go), with no significant interaction between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractors). Finally, the enhancement hypothesis (Fig. 1 right panel) predicted that inhibition- and emotion-related processes would interact in a mutually-reinforcing or mutually-enhancing fashion. This mutual enhancement would cause aversive NoGo trial activation in IFG to be larger than the sum of inhibition activation (neutral NoGo– neutral Go) and emotion activation (aversive NoGo–neutral Go), with a significant statistical interaction between response inhibition and emotional context. We also carried out exploratory analyses to search for potential interactions between response inhibition (NoGo vs. Go) and emotion processing (aversive vs. neutral task-irrelevant distractors) in parts of the brain other than IFG. Methods This study was approved by the Health Research Ethics Board at the University of Alberta. Participants Participants were twenty young adults (13 female and 7 male, age range 18–28 years, mean age 22.5 ± 2.4 years) recruited from the University of Alberta campus population. 16 participants were righthanded, 2 were left-handed, and 2 were ambidextrous, based on the

Additive Hypothesis

Enhancement Hypothesis

0.6

0.6

0.6

0.4

0.4

0.4

0.2

0.2

0.2

BOLD

Neutral Go Aversive Go Neutral NoGo

0

0 0

4

8

Time (s)

12

Aversive NoGo

0 0

4

8

Time (s)

12

0

4

8

12

Time (s)

Fig. 1. Depiction of three hypotheses on the interaction of inhibition- and emotion-related activity in the inferior frontal gyrus (IFG): (left) interference hypothesis, (middle) additive hypothesis, (right) enhancement hypothesis. Each panel depicts predicted activation timecourses for four trial types: neutral Go, aversive Go, neutral NoGo, and aversive NoGo. Only the aversive NoGo timecourse differs among the three hypotheses; the other timecourses are identical. See Introduction for details.

436

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Edinburgh Handedness Inventory (Oldfield, 1971). All participants spoke English fluently and gave informed, written consent to participate in the study. Participants had no history or existing diagnosis of any psychiatric disorder, neurological disorder, or learning disability, based on self report. Task We used a variant of the Go/NoGo task (see Donders, 1868; Hester and Garavan, 2004) with emotional distractor pictures presented simultaneously with the Go and NoGo stimuli. In each trial, the participant was presented for 2 s with either a Go stimulus or a NoGo stimulus. Go/NoGo stimuli were a circle or a square (see Fig. 2). The shape to trial type assignment was counterbalanced across participants. Each Go and NoGo stimulus was presented superimposed over a distractor image taken from the International Affective Pictures System (IAPS) (Lang et al., 2008). Each IAPS image depicted a neutral or aversive scene. On a given trial, the Go or NoGo stimulus along with the distractor picture was presented simultaneously for one fMRI scan volume (2 s), during which the participant had either to press a button with their right index finger on Go trials or withhold the button press on NoGo trials. We presented Go and NoGo trials at a 4:1 ratio to make the Go response more automatic (prepotent). In total, we had four trial types obtained by crossing Go vs. NoGo with neutral vs. aversive distractor images: neutral Go, neutral NoGo, aversive Go, and aversive NoGo. Participants were instructed to fixate on a dot at screen center between trials (Fig. 2B). We used a rapid event-related design in which each Go or NoGo trial lasted 2 s, with inter-trial intervals of 2, 4, and 6 s (mean 4 s, distributed 30% 2 s, 40% 4 s, 30% 6 s). Trial sequences and timings were computed to ensure “separability” (linear independence, see Burock et al., 1998) of the different trial types using in-house software programmed in Python. Trial sequences were counterbalanced to avoid first-order interaction effects between adjacent trials. Each of the four trial types was preceded in equal proportions by the 2, 4, and 6 s inter-trial intervals to avoid interaction of BOLD non-linearity with inter-trial intervals and trial types. For each participant, we collected 204 trials split over four functional runs, resulting in a total of 84 neutral Go trials, 80 aversive Go trials, 20 neutral NoGo trials, and 20 aversive NoGo trials. The first trial of every run was a neutral Go trial. Run duration was 330 s. After scanning, participants rated all 204 IAPS distractor images used in the fMRI task for valence and arousal using the 9 point Likert scale described in Lang et al. (2008). MRI scanning Participants underwent magnetic resonance imaging on a 4.7 Tesla Varian Inova scanner at the Peter S. Allen MR Research Centre at the University of Alberta. We used an echo planar imaging (EPI) sequence for T2*-weighted blood oxygenation level dependent (BOLD) fMRI. EPI parameters were: volume time 2 s, single shot, repeat time (TR) 2 s,

A

echo time (TE) 19 ms, 3 mm isotropic voxels, 80× 80 in-plane grid, 240 × 240 mm in-plane field of view (FOV), 3 mm slice thickness, 36 axial slices, 108 mm through-plane coverage, interleaved slice collection order (odds then evens starting at the bottom). The sequence included partial k-space collection dropping the first 16 lines of k-space in the phase-encode direction (anterior–posterior). The fMRI scanning volume covered the entire cerebral cortex except for the ventral–posterior tip of occipital cortex in participants with larger heads. For each participant, we also collected a T1-weighted magnetization-prepared rapid acquisition gradient echo (MPRAGE) structural scan with parameters: TR 9.4 ms, TI 300 ms, TD (relaxation delay time after readout prior to inversion) 300 ms, linear phase encoding, TE 3.7 ms, matrix 240×192×128 (readout×phase encode×slice encode), FOV 240×192×192 mm3, 1×1×1.5 mm voxels, whole brain coverage.

Analysis Behavioral data (error rates, latencies) and IAPS picture ratings were analyzed using mixed effects ANOVAs in the R statistical programming language. We used SPM8 and in-house MATLAB code for preprocessing. Preprocessing for each participant included: (1) estimation of parameters for 6 parameter rigid body motion in SPM8 without reslicing, (2) slice-timing correction on raw (not motion corrected) data using spline temporal interpolation in MATLAB, (3) spline spatial interpolation of each fMRI volume in MATLAB to effect motion correction using saved motion parameters from step (1), (4) coregistration of fMRI data to MPRAGE anatomical scan in SPM8, (5) non-linear spatial warping (estimation and interpolation) of MPRAGE anatomical volume to MNI T1 template space at 1×1×1 mm resolution in SPM8, (6) interpolation of fMRI volumes into the T1 template space at 3×3×3 mm spatial resolution using warping parameters from step (5), (7) 8 mm full width at half maximum (FWHM) Gaussian spatial filter of fMRI volumes in SPM8. Motion parameter estimation and slice time correction were done independently to prevent the two corrections from influencing each other. FMRI data were analyzed hierarchically with 20 separate withinsubjects statistical analyses followed by a between-subjects “summary statistics” mixed-effects analysis (Worsley et al., 2002). The withinsubjects analyses used a general linear model (GLM) for each subject consisting of five sets of finite impulse response (FIR) predictors, one set for each of the four trial types (neutral Go, aversive Go, neutral NoGo, aversive NoGo) and one set for error trials (collapsed across trial types). Error trials were rare (0 to 10.0% of trials, per subject, as described in the Results). The model included 10 FIR impulse predictors (corresponding to 10 functional volumes) per set. For each run, the model also included nuisance predictors: constant run offset, linear drift, cosine and sine with period equal to twice the run length, 6 rigid body motion parameters, and 6 impulses at the start of each run for spin saturation. We excluded voxels outside the brain with a manuallyconstructed mask. The mask included 54,864 voxels (size 3×3× 3 mm) inside the brain.

B

Fig. 2. Emotional Go/NoGo Task. A: Four trial types derived by combining square vs. circle Go/NoGo stimuli with neutral vs. aversive distractor pictures. (Mapping was counter-balanced across subjects.) B: Segment of two trials with 2–6 s fixation intertrial intervals (ITIs) interleaved.

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

437

Fig. 3. Main effects statistical contrast map for NoGo–Go trials, collapsed across aversive and neutral distractors. Neurological convention is used: right side of axial image represents right side of the brain. Yellow/red regions exhibited higher activation for NoGo trials. Blue regions exhibited higher activation for Go trials. Numbers above and left of each slice denote Z coordinates in MNI space in mm. All results p b 0.05 corrected for multiple comparisons (between subjects df = 19).

For each participant, we computed beta weights using correction for autocorrelated (colored) noise. Ten autocorrelation coefficients (lags of 1 to 10 volume times) were computed for each functional slice across the whole brain using the residuals from a non-corrected initial GLM fit. We pre-whitened the design matrix and each voxel's time course to compute auto-correlation-corrected beta weights as described in Burock and Dale (2000) and Worsley et al. (2002). For each subject separately, we computed three statistical contrast maps (two-tailed T statistic maps) from the GLM beta weights. To assess BOLD activity related to behavioral inhibition, we compared NoGo trials against Go trials using the contrast (aversive NoGo+neutral NoGo)– (aversive Go+neutral Go). We compared aversive picture trials with neutral picture trials using the contrast (aversive NoGo+aversive Go)–(neutral NoGo+neutral Go) to determine the effect of emotional context. To investigate the interaction of response inhibition with emotional context, we computed the interaction contrast (aversive NoGo– aversive Go)–(neutral NoGo–neutral Go). Contrasts were computed using mean activation across the 3rd and 4th time points of the FIR

timecourses. The 3rd and 4th time points correspond to 4 and 6 s from trial start, and we chose them a priori because the BOLD hemodynamic peak typically occurs around 4 to 6 s. For each of the three contrasts listed above, we combined the subject-specific statistical maps using the mixed-effects analysis of Worsley et al. (2002). Statistical maps were thresholded first voxelwise at p b 0.05 (|T| >1.984, two-tailed, df= 100) and secondly with a cluster mass threshold. Cluster mass is the sum of T values for all voxels in a cluster (see Bullmore et al., 1999; Holmes, 1994; Zhang et al., 2009), where voxels were 3 × 3 × 3 mm in our case. Because we used two-tailed T-tests, cluster mass could be negative. Only clusters whose absolute cluster mass was greater than the threshold were accepted. We used Monte Carlo simulation to derive a cluster mass threshold of 495 that controlled the group error rate at p b 0.05 for multiple comparisons not only across the voxel population but also across the three statistical contrasts we computed. The three contrasts described above could be driven by different sub-contrasts in different voxels. For example, in regions where we

438

Table 1 Region of interest (ROI) data from three statistical contrast maps. Region of interest

Centroid location (MNI coordinates in mm) X

(Go >NoGo) L pre/postcentral gyrus L dorsal pre/postcentral gyrus Bilateral cingulate gyrus R insula R insula/posterior sylvian fissure/ inferior Postcentral gyrus L insula L posterior insula L putamen/globus pallidus

Z

Neutral Go

Aversive Go

Neutral NoGo

T Values for 8 contrasts from region of interest analysis

Aversive NoGo

Localizer

NoGo– Neutral

Aversive– Interaction Neutral: Neutral NoGo–Go

44

27

−1

8100

0.09 ± 0.01

0.14 ± 0.01

0.14 ± 0.02

0.21 ± 0.02

9.2⁎⁎⁎⁎

4.2⁎⁎⁎

4.3⁎⁎⁎

−35

27

−6

1512

0.04 ± 0.02

0.12 ± 0.02

0.11 ± 0.02

0.18 ± 0.02

4.6⁎⁎⁎

3.8⁎⁎

3.0⁎⁎

38 48 −37 −19 12

48 25 10,071 21 30 5967 23 29 9585 30 −15 6831 23 28 5211

0.03 ± 0.01 0.02 ± 0.01 0.13 ± 0.01 0.18 ± 0.01 0.07 ± 0.01 0.11 ± 0.01 −0.01 ± 0.02 0.04 ± 0.02 −0.04 ± 0.02 −0.02 ± 0.02

0.06 ± 0.01 0.16 ± 0.02 0.12 ± 0.02 0.04 ± 0.02 0.04 ± 0.02

0.07 ± 0.01 0.26 ± 0.02 0.15 ± 0.01 0.12 ± 0.02 0.05 ± 0.02

3.0⁎⁎ 6.5⁎⁎⁎⁎ 5.9⁎⁎⁎⁎ 2.0 0.3

4.3⁎⁎⁎

4.1⁎⁎⁎

3.3⁎⁎

−0.9

3.4⁎⁎

2.5⁎

4.5⁎⁎⁎

1.8

3.8⁎⁎ 3.6⁎⁎ 4.0⁎⁎⁎ 5.3⁎⁎⁎⁎ 4.5⁎⁎⁎

1.0 1.2 5.9⁎⁎⁎⁎ 1.5 −0.5 2.8⁎ 3.0⁎⁎ 0.6 0.7 −0.7

2.7⁎ 1.8 3.2⁎⁎ 2.7⁎ 3.6⁎⁎

3.3⁎⁎ 3.9⁎⁎⁎ 2.3⁎ 3.5⁎⁎ 2.8⁎

0.4 1.0

2.8⁎ 2.9⁎⁎

0.5 −0.6 −0.4 0.4 1.5

0.06 ± 0.01 0.38 ± 0.01

0.06 ± 0.01 0.46 ± 0.01

0.11 ± 0.02 0.43 ± 0.02

0.13 ± 0.02 0.53 ± 0.02

4.2⁎⁎⁎ 11.9⁎⁎⁎⁎

4.2⁎⁎⁎ 4.6⁎⁎⁎

0.7 5.9⁎⁎⁎⁎

−64 53 13,284 −53 53 19,170 −80 30 17,496 −16 −11 14,742 −48 12 19,737

0.12 ± 0.01 0.10 ± 0.01 0.29 ± 0.01 0.01 ± 0.01 0.06 ± 0.01

0.14 ± 0.01 0.12 ± 0.01 0.34 ± 0.01 0.03 ± 0.01 0.10 ± 0.01

0.16 ± 0.02 0.17 ± 0.02 0.35 ± 0.02 0.06 ± 0.01 0.11 ± 0.02

0.20 ± 0.02 0.18 ± 0.02 0.39 ± 0.02 0.09 ± 0.01 0.18 ± 0.02

5.4⁎⁎⁎⁎ 8.7⁎⁎⁎⁎ 11.1⁎⁎⁎⁎ 2.9⁎⁎ 5.7⁎⁎⁎⁎

3.6⁎⁎ 4.2⁎⁎⁎ 4.5⁎⁎⁎ 4.0⁎⁎⁎ 4.6⁎⁎⁎

1.8 0.9 4.0⁎⁎⁎ 1.5 4.4⁎⁎⁎

6993 5184 3186

−0.00 ± 0.01 0.22 ± 0.01 0.19 ± 0.01

0.02 ± 0.01 0.27 ± 0.01 0.30 ± 0.01

0.05 ± 0.02 0.25 ± 0.01 0.20 ± 0.02

0.12 ± 0.02 0.33 ± 0.01 0.41 ± 0.02

1.7 8.5⁎⁎⁎⁎ 6.2⁎⁎⁎⁎

3.9⁎⁎⁎ 5.4⁎⁎⁎⁎ 3.1⁎⁎

2.0 5.2⁎⁎⁎⁎ 7.7⁎⁎⁎⁎

−43 −19 −21 −18 −1 −4 45 3

56 24,057 72 8748 58 6912 16 4239

0.24 ± 0.01 0.14 ± 0.01 0.11 ± 0.01 0.08 ± 0.01

0.22 ± 0.01 0.13 ± 0.01 0.11 ± 0.01 0.06 ± 0.01

0.06 ± 0.01 0.02 ± 0.02 0.04 ± 0.01 0.02 ± 0.01

0.09 ± 0.01 0.04 ± 0.02 0.07 ± 0.02 0.02 ± 0.01

6.6⁎⁎⁎⁎ 3.3⁎⁎ 5.2⁎⁎⁎⁎ 4.3⁎⁎⁎

64 −11 −33 −4 −55 −22 −17 −14

42 7884 13 13,959 29 6804 12 4644

0.07 ± 0.01 0.10 ± 0.01 0.11 ± 0.01 0.09 ± 0.01

0.05 ± 0.01 0.09 ± 0.01 0.09 ± 0.01 0.10 ± 0.01

−0.00 ± 0.01 0.03 ± 0.01 0.04 ± 0.02 0.04 ± 0.01

0.02 ± 0.02 0.04 ± 0.01 0.03 ± 0.02 0.07 ± 0.01

1.9 −4.3⁎⁎⁎ 5.8⁎⁎⁎⁎ −4.0⁎⁎⁎ 6.3⁎⁎⁎⁎ 4.3⁎⁎⁎ 4.7⁎⁎⁎ −2.9⁎⁎

24 −26 −24 53 60

−56 −44 39 −53 −46 −73

From Aversive–Neutral Contrast (Aversive >Neutral) R superior frontal sulcus 31 R middle frontal gyrus 48 R inferior frontal gyrus/operculum 47 (vlPFC) L inferior frontal gyrus/operculum (vlPFC) −33 L inferior frontal sulcus −38

−1 4 15

34 7 31

50 4347 42 36,126 9 24,462

29 16

−5 20,439 23 19,710

−0.03 ± 0.01 −0.02 ± 0.01 −0.05 ± 0.01 −0.00 ± 0.01 −1.7 0.09 ± 0.01 0.12 ± 0.0.1 0.08 ± 0.01 0.16 ± 0.01 7.4⁎⁎⁎⁎ 0.09 ± 0.01 0.14 ± 0.01 0.11 ± 0.01 0.20 ± 0.01 8.1⁎⁎⁎⁎ 0.06 ± 0.01 0.05 ± 0.01

0.14 ± 0.01 0.09 ± 0.01

0.08 ± 0.02 0.05 ± 0.01

0.17 ± 0.02 0.11 ± 0.01

5.9⁎⁎⁎⁎ 5.2⁎⁎⁎⁎

NoGo: Go: Aversive– Aversive– Neutral Neutral

2.8⁎

55 15,417 27 14,364

37 −43 39 −57

Aversive: NoGo–Go

−5.7⁎⁎⁎⁎ 0.7 −4.0⁎⁎⁎ 0.6 −3.5⁎⁎ 1.0 −4.2⁎⁎⁎ −0.5

0.6 −0.3 −1.0 2.5⁎

0.6

−0.7 4.3⁎⁎⁎ 3.2⁎⁎ 2.3⁎ 1.6

1.2 4.3⁎⁎⁎ 1.5 2.0 0.0

3.0⁎⁎ 4.0⁎⁎⁎

0.3 5.7⁎⁎⁎⁎

0.7 4.4⁎⁎⁎

2.8⁎ 3.9⁎⁎ 3.8⁎⁎ 2.8⁎ 3.5⁎⁎

2.7⁎ 2.9⁎ 3.2⁎⁎ 3.4⁎⁎ 4.1⁎⁎⁎

2.1⁎ 1.9 4.1⁎⁎⁎ 1.3 3.6⁎⁎

1.3 0.2 2.3⁎ 1.0 3.9⁎⁎⁎

0.6 1.9 2.9⁎⁎

3.0⁎⁎ 2.2⁎ 0.3

3.1⁎⁎ 5.3⁎⁎⁎⁎ 4.1⁎⁎⁎

2.0 4.0⁎⁎⁎ 6.7⁎⁎⁎⁎

1.6 4.2⁎⁎⁎ 6.7⁎⁎⁎⁎

2.3⁎ 1.4 1.2 0.6

−6.7⁎⁎⁎⁎ −4.6⁎⁎⁎ −4.1⁎⁎⁎ −3.5⁎⁎

−4.3⁎⁎⁎ −3.1⁎⁎ −2.1⁎ −2.9⁎⁎

−1.3 −0.6 −0.1 −1.3

1.8 1.2 1.3 0.0

1.7 0.7 0.5 1.4

−5.0⁎⁎⁎⁎ 4.3⁎⁎⁎ −4.3⁎⁎⁎ −3.5⁎⁎

−2.3⁎ −0.3⁎⁎ −2.8⁎

−1.0 −1 −2.0 2.3⁎

1.3 0.2 −0.4 2.2⁎

−1 −1.2 1.2

0.3 0.9 3.0⁎⁎

3.3⁎⁎ 6.7⁎⁎⁎⁎ 6.3⁎⁎⁎⁎

2.1 3.2⁎⁎ 2

2.7⁎ 1.5

4.3⁎⁎⁎⁎ 4.6⁎⁎⁎

0.2 1.2

1.8 0.4

−1.6

1.4 2.6⁎ 3.8⁎⁎

1.5 3.6⁎⁎ 4.7⁎⁎⁎

3.0⁎⁎ 5.5⁎⁎⁎⁎ 5.2⁎⁎⁎⁎

1.8 1.8

6.0⁎⁎⁎⁎ 4.2⁎⁎⁎

3.0⁎⁎ 3.4⁎⁎

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

From NoGo–Go contrasts (NoGo > Go) R inferior frontal gyrus/operculum (VlPFC) L inferior frontal gyrus/operculum (VlPFC) R anterior superior frontal sulcus R inferior frontal sulcus L inferior frontal sulcus L orbitofrontal cortex Bilateral medial orbitofrontal cortex R anterior intraparietal sulcus R posterior intraparietal sulcus R dorsal parieto-occipital sulcus/ posterior Intraparietal sulcus L anterior intraparietal sulcus L posterior intraparietal sulcus R anterior middle temporal gyrus R posterior middle temporal gyrus/angular gyrus L middle temporal gyrus R inferior temporal cortex L lateral occipital sulcus

Y

Volume BOLD amplitude (% ± standard deviation) (mm3)

From Interaction Contrast R frontal eye fields R precentral sulcus R central sulcus R postcentral sulcus L dorsal precentral gyrus/postcentral gyrus R cingulate gyrus L cingulate gyrus/superior frontal gyrus R anterior insula R insula R caudate/putamen R putamen L caudate R posterior middle temporal gyrus/ angular gyrus L posterior middle temporal gyrus L deep posterior middle temporal gyrus

−31 1 6

−3 64 11

21 −5 4 −58 −29 32 25 −25 −23

60 61 15 −9 7 −43 −83 −80 −46

−46 28 −91 28 −24 −27 23 25 2

7.4⁎⁎⁎⁎ −0.9 1.3 0.6 4.6⁎⁎⁎ 0.5

5.3⁎⁎⁎⁎ 3.4⁎⁎ 2.9⁎⁎

1.8 1.2 0.8

−2 −0.4 0.1

0.2 1.3 0.9

4.2⁎⁎⁎ 3.4⁎⁎ 2.1

4.0⁎⁎⁎ 2.7⁎ 2.5⁎

4.1⁎⁎⁎ 4.8⁎⁎⁎ 3.3⁎⁎

1.5 −0.2 −0.2 −3.0⁎⁎

2.7⁎ 1.4 1.4 1 0.9 3.2⁎⁎ 3.0⁎⁎ 2.9⁎⁎

4.0⁎⁎⁎ 3.8⁎⁎ 3.1⁎⁎

3.7 4.0⁎⁎⁎ 3.4⁎⁎ 4.7⁎⁎⁎ 5.7⁎⁎⁎⁎ 3.9⁎⁎⁎

0.7 1.1 1.3 2.8⁎ 0.5 0.9 0.8 0.2 1

2

1 4.1⁎⁎⁎ 2.7 3.8⁎⁎ 5.4⁎⁎⁎⁎ 4.2⁎⁎⁎

2.8⁎ 3.4⁎⁎ 2.5⁎ 3.6⁎⁎ 2.3⁎ 2.6⁎ 3.2⁎⁎ 3.4⁎⁎ 2.8⁎

0.8 2.6⁎ 3.4⁎⁎

5.5⁎⁎⁎⁎ 4.8⁎⁎⁎ 6.4⁎⁎⁎⁎ 4.7⁎⁎⁎ 3.6⁎⁎ 7.8⁎⁎⁎⁎

1.2 0.5 0.8 1.5 1.4 2.9⁎⁎

1.3 1.4 1.3 −0.1 0.7 0.9

3.1⁎⁎ 2.7⁎ 1.9 1.1 2.9⁎ 4.2⁎⁎⁎

5.5⁎⁎⁎⁎ 4.9⁎⁎⁎⁎ 5.9⁎⁎⁎⁎ 4.7⁎⁎⁎ 3.6⁎⁎ 5.9⁎⁎⁎⁎

4.3⁎⁎⁎ 3.0⁎⁎ 4.2⁎⁎⁎ 3.7⁎⁎ 2.8⁎ 7.3⁎⁎⁎⁎

0.26 ± 0.02 0.16 ± 0.02 0.15 ± 0.02 0.17 ± 0.02 0.17 ± 0.02 0.15 ± 0.02 0.15 ± 0.02 0.30 ± 0.02 0.21 ± 0.02

4.9⁎⁎⁎ 2.9⁎⁎ 6.8⁎⁎⁎⁎ 1.1 6.3⁎⁎⁎⁎ −0.1 5.5⁎⁎⁎⁎ 0.3 7.4⁎⁎⁎⁎ 0.6 ⁎⁎⁎⁎ 5.6 2 3.2⁎⁎ 2 8.3⁎⁎⁎⁎ 1.1 5.4⁎⁎⁎⁎ −0.1

6.8⁎⁎⁎⁎ 5.8⁎⁎⁎⁎ 6.6⁎⁎⁎⁎ 4.1⁎⁎⁎ 5.2⁎⁎⁎⁎ 5.8⁎⁎⁎⁎ 4.1⁎⁎⁎ 4.5⁎⁎⁎ 4.3⁎⁎⁎

2.4⁎ 1.3 1.4 1.2 1.2 0.7 1.7 1.7 1.6

0.5 −0.2 −0.9 −0.3 −0.4 1.2 0.7 −0.1 −1

3.7⁎⁎ 1.6 0.7 0.8 1.1 1.9 2.4⁎ 2.3⁎ 1

6.2⁎⁎⁎⁎ 5.3⁎⁎⁎⁎ 5.9⁎⁎⁎⁎ 4.1⁎⁎⁎ 4.8⁎⁎⁎⁎ 5.6⁎⁎⁎⁎ 3.5⁎⁎ 3.1⁎⁎ 3.2⁎⁎

5.8⁎⁎⁎⁎ 3.9⁎⁎ 4.4⁎⁎⁎ 3.3⁎⁎ 3.7⁎⁎ 3.5⁎⁎ 3.1⁎⁎ 4.0⁎⁎⁎ 3.8⁎⁎

0.08 ± 0.02 0.02 ± 0.02

0.15 ± 0.02 0.09 ± 0.02

6.4⁎⁎⁎⁎ −0.1 3.8⁎⁎ −0.6

3.8⁎⁎ 4.1⁎⁎⁎

0.8 1.3

−0.5 −1.3

0.5 0.1

4.9⁎⁎⁎⁎ 3.8⁎⁎

2.7⁎ 3.0⁎⁎

−1.6 2.6⁎ −0.6 4.2⁎⁎⁎ −1.4 2.1⁎ −3.9⁎⁎⁎ 0.0 −5.0⁎⁎⁎⁎ −2.0

0.09 ± 0.01 0.00 ± 0.02 0.08 ± 0.01

0.11 ± 0.01 0.06 ± 0.02 0.12 ± 0.01

0.06 ± 0.01 −0.02 ± 0.02 0.08 ± 0.02

0.11 ± 0.01 0.08 ± 0.02 0.14 ± 0.02

2619 2970 18,738 6102 2106 7398 10,962 14,985 22,464

−0.5 ± 0.02 −0.07 ± 0.02 0.08 ± 0.01 0.10 ± 0.01 0.04 ± 0.01 0.07 ± 0.01 0.50 ± 0.01 0.24 ± 0.01 0.02 ± 0.01

0.02 ± 0.02 0.00 ± 0.02 0.11 ± 0.01 0.11 ± 0.01 0.08 ± 0.01 0.10 ± 0.01 0.55 ± 0.01 0.30 ± 0.01 0.05 ± 0.01

−0.01 ± 0.03 −0.07 ± 0.03 0.08 ± 0.01 0.06 ± 0.02 0.05 ± 0.02 0.11 ± 0.01 0.53 ± 0.02 0.29 ± 0.02 0.03 ± 0.01

0.09 ± 0.03 0.6 2.6⁎ 0.04 ± 0.03 −0.9 0.8 0.14 ± 0.01 6.7⁎⁎⁎⁎ 0.7 0.13 ± 0.02 6.8⁎⁎⁎⁎ −1.2 0.11 ± 0.02 3.4⁎⁎ 0.9 0.16 ± 0.01 4.8⁎⁎⁎ 3.2⁎⁎ 0.60 ± 0.02 11.8⁎⁎⁎ 3.1⁎⁎ 0.35 ± 0.02 10.3⁎⁎⁎⁎ 3.7⁎⁎ 0.09 ± 0.01 3.1⁎⁎ 1.5

−20 15,093 −10 2565 −20 4671 −19 7236 −6 3024 21 39,636

0.05 ± 0.01 0.04 ± 0.01 0.05 ± 0.01 0.04 ± 0.01 0.02 ± 0.01 0.20 ± 0.01

0.13 ± 0.01 0.09 ± 0.01 0.11 ± 0.01 0.10 ± 0.01 0.06 ± 0.01 0.27 ± 0.01

0.07 ± 0.02 0.07 ± 0.02 0.07 ± 0.02 0.04 ± 0.02 0.03 ± 0.02 0.21 ± 0.01

0.18 ± 0.02 0.14 ± 0.02 0.15 ± 0.02 0.13 ± 0.02 0.11 ± 0.02 0.34 ± 0.01

6.8⁎⁎⁎⁎ 4.3⁎⁎⁎ 7.1⁎⁎⁎⁎ 4.9⁎⁎⁎⁎ 2.4⁎ 9.5⁎⁎⁎⁎

−68 15 18,198 −5 −7 11,799 −8 −4 9585 3726 −19 −1 −22 −5 3537 −2 −14 3888 −61 59 11,502 −45 7 11,961 −58 12 30,753

0.09 ± 0.01 0.08 ± 0.01 0.08 ± 0.01 0.10 ± 0.01 0.10 ± 0.01 0.04 ± 0.01 0.04 ± 0.02 0.23 ± 0.01 0.14 ± 0.01

0.17 ± 0.01 0.13 ± 0.01 0.13 ± 0.01 0.15 ± 0.01 0.15 ± 0.01 0.10 ± 0.01 0.09 ± 0.02 0.27 ± 0.01 0.19 ± 0.01

0.10 ± 0.02 0.07 ± 0.02 0.06 ± 0.02 0.09 ± 0.02 0.09 ± 0.02 0.06 ± 0.02 0.05 ± 0.02 0.22 ± 0.02 0.11 ± 0.02

0.09 ± 0.01 0.05 ± 0.01

0.14 ± 0.01 0.09 ± 0.01

44 19 36 12 35 0 11 −41 −59 −17 49 −65

−1 −17 −2 −21

52 14,580 39 29,754 64 18,738 12 7 42 33 −7 58 23 30 58

11 17,712 −3 3456

3.1⁎⁎ 2.6⁎ 2.3⁎

0.3 2.2⁎ 1.8 2.8⁎ 0.5

41 1 47 16 53 −2 58 −17 −24 −26

54 39 40 42 61

6912 2592 1485 3942 6399

0.05 ± 0.01 0.15 ± 0.01 0.05 ± 0.01 0.08 ± 0.01 0.10 ± 0.01

0.07 ± 0.01 0.20 ± 0.01 0.07 ± 0.01 0.07 ± 0.01 0.10 ± 0.01

0.03 ± 0.01 0.14 ± 0.02 0.03 ± 0.01 0.02 ± 0.02 0.02 ± 0.01

0.10 ± 0.01 0.27 ± 0.02 0.10 ± 0.01 0.07 ± 0.02 0.06 ± 0.01

3.8⁎⁎ 0.6 6.8⁎⁎⁎⁎ 2.3⁎ 3.8⁎⁎ 0.3 3.3⁎⁎ −2.7⁎ 4.8⁎⁎⁎ −3.9⁎⁎

5.0⁎⁎⁎⁎ 7.1⁎⁎⁎⁎ 4.5⁎⁎⁎ 2.0 1.9

3.7⁎⁎ 3.9⁎⁎ 2.7⁎ 2.8⁎ 2.6⁎

18 −1 −12 5 37 31 38 8 26 24 34 −11 −21 −24 52 −61

58 2592 47 3996 16 837 28 1350 11 5697 16 459 23 2133 18 13,743

0.04 ± 0.01 0.08 ± 0.01 0.07 ± 0.01 0.09 ± 0.01 0.04 ± 0.01 0.06 ± 0.01 0.03 ± 0.01 0.16 ± 0.01

0.04 ± 0.01 0.08 ± 0.01 0.09 ± 0.01 0.10 ± 0.01 0.03 ± 0.01 0.04 ± 0.01 0.02 ± 0.01 0.24 ± 0.01

0.02 ± 0.01 0.05 ± 0.01 0.07 ± 0.01 0.07 ± 0.01 −0.00 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.16 ± 0.01

0.05 ± 0.01 0.11 ± 0.01 0.13 ± 0.01 0.12 ± 0.01 0.05 ± 0.01 0.05 ± 0.01 0.04 ± 0.01 0.32 ± 0.01

2.5⁎ 7.9⁎⁎⁎⁎ 5.4⁎⁎⁎⁎ 4.2⁎⁎⁎ 2.4⁎ 2.3⁎

−0.2 0.1 1.8 −0.3 −0.7 −1.1 1.9 0.1 8.8⁎⁎⁎⁎ 3.4⁎⁎

2.0 3.9⁎⁎⁎ 3.3⁎⁎ 2.6⁎ 2.8⁎ 1.4 1.3 9.0⁎⁎⁎⁎

3.0⁎⁎ 3.1⁎⁎ 2.7⁎ 2.4⁎ 3.6⁎⁎ 2.8⁎ 2.4⁎ 4.8⁎⁎⁎

−2.0 −1.9 −0.1 −1.9 −3.1⁎⁎ −2.5⁎ −1.5 −07

−44 −68 −32 −63

16 24

0.14 ± 0.01 0.02 ± 0.01

0.24 ± 0.01 0.01 ± 0.01

0.12 ± 0.02 −0.01 ± 0.01

0.33 ± 0.02 0.02 ± 0.02

2.4⁎ 6.4⁎⁎⁎⁎ 0.6 −0.4

7.8⁎⁎⁎⁎ 1.9

4.4⁎⁎⁎ 3.4⁎⁎

−1.5 −2.7⁎

5400 5832

1.7 2.9⁎⁎ 2.2⁎ −0.7 −0.6

5.1⁎⁎⁎⁎ 6.4⁎⁎⁎⁎ 4.0⁎⁎⁎ 2.8⁎ 2.5⁎

1.3 1.9 3.1⁎⁎ 1.3 1.9 0.6 1.5 6.0⁎⁎⁎⁎

−0.9 0.9 1.4 0.7 −1.3 −1.1 −0.9 6.3⁎⁎⁎⁎

2.7⁎ 4.0⁎⁎⁎ 3.4⁎⁎ 2.9⁎⁎ 3.7⁎⁎ 2.3⁎ 2.0 9.9⁎⁎⁎⁎

4.5⁎⁎⁎ 1.9

6.6⁎⁎⁎⁎ −0.9

7.2⁎⁎⁎⁎ 3.4⁎⁎

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

L frontal eye fields Bilateral anterior medial frontal gyrus Bilateral posterior medial frontal gyrus Bilateral inferior medial frontal cortex L medial gyrus Bilateral anterior cingulate cortex L inferior precentral gyrus L insula R anterior intraparietal sulcus R posterior intraparietal sulcus L posterior intraparietal sulcus L posterior cingulate gyrus/intraparietal sulcus R temporal pole R temporal pole R medial temporal L temporal pole L superior temporal sulcus R posterior middle temporal gyrus/ angular gyrus L posterior middle temporal gyrus R amygdala/anterior hippocampus L amygdala/anterior hippocampus R hippocampus L hippocampus/entorhinal cortex L entorhinal cortex R precuneus R ventral parieto−occipital sulcus Bilateral anterior medial occipital cortex/ posterior cingulate gyrus Bilateral striatum/thalamus Bilateral mesencephalon

⁎

p b 0.05 mixed effects T-test, 19 df. p b 0.01 mixed effects T-test, 19 df. p b 0.001 mixed effects T-test, 19 df. ⁎⁎⁎⁎ p b 0.0001 mixed effects T-test, 19 df. ⁎⁎

⁎⁎⁎

439

440

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

NoGo - Go Contrast

Right IFG Time courses

BOLD (%)

0.3 Neutral Go Aversive Go Neutral NoGo Aversive NoGo

0.2 0.1 0 −0.1

0

5

10

15

20

Time (s)

NoGo - Go Contrast

2002) nor cluster-mass thresholding for the ROI analysis, as these steps do not make sense in this context. Spatial regularization and cluster thresholding utilize the spatial aspect of three-dimensional data. By averaging timecourses across voxels within each region in the ROI analysis, we removed the spatial aspect of the data.) In addition to the three contrasts described above, we computed five additional statistical contrasts for the ROI analysis: (neutral Go+neutral NoGo+aversive Go+aversive NoGo), (neutral NoGo–neutral Go), (aversive NoGo–aversive Go), (aversive Go–neutral Go), and (aversive NoGo–neutral NoGo). Because these were post-hoc tests designed only to give insight into what was driving the primary, voxel-wise statistical results, we did not correct the ROI results for multiple comparisons.

Left IFG Timecourses Results

BOLD (%)

0.3

Neutral Go Aversive Go Neutral NoGo Aversive NoGo

0.2 0.1 0 −0.1

0

5

10

15

20

Time (s) Fig. 4. Left panels: Two slices from response inhibition statistical contrast map (aversive NoGo+neutral NoGo)–(aversive Go+neutral Go). Yellow and blue regions showed greater activation for NoGo and Go trials, respectively. All results pb 0.05 corrected for multiple comparisons. Neurological convention used. Color bars indicate scaling for T values. Numbers in upper left corners denote the slices' Z coordinates in MNI space in mm. Right panels: Deconvolved timecourses for four trial types from the right and left inferior frontal gyrus (IFG) regions outlined in green on the left column panels. The right IFG and left IFG did not exhibit significant interaction effects, that is, no significant NoGo vs. Go by aversive vs. neutral distractors interaction contrast (see Table 1).

observed a significant interaction contrast, this could potentially have been caused by a large (aversive NoGo–aversive Go) difference combined with a small (neutral NoGo–neutral Go) difference. Alternatively, a significant interaction contrast could be caused by a large (neutral Go–neutral NoGo) difference combined with a small (aversive NoGo–aversive Go) difference. Other combinations of activity patterns could also drive the interaction contrast. To tease apart these effects, we followed the statistical map analysis with a region of interest (ROI) analysis that tested more focused contrasts among the four trial types. For each of the three maps described above, from all of the clusters that passed the multiple comparison threshold, we defined regions of interest using an automated algorithm that we coded in MATLAB. This algorithm grew a region around each statistical peak voxel, with the constraint that each seed peak voxel had to be 30 mm away from the nearest seed peak voxel. Each region had to contain at least 20 functional voxels (implying 540 mm3 minimum ROI volume). Regions smaller than 20 voxels were absorbed into the nearest larger region if possible. If not possible because the small region was separate from and did not abut any larger region, it was left alone. For those significant clusters (from one of the three statistical maps) that contained only a single statistical peak, the ROI extraction algorithm defined the entire cluster as one region of interest. Some of the larger significant clusters contained multiple statistical peaks (further than 30 mm from each other), and in these cases, the ROI extraction process split these large clusters into several smaller regions of interest. For each region of interest, we computed mean time courses across the region's voxel population for each participant. We then did a hierarchical analysis on these mean time courses similar to the voxel-wise analysis described above. (We did not do spatial regularization (Worsley et al.,

Behavior Rates of commission errors on NoGo trials were low but significantly above zero with a mean and standard deviation of 3.5± 3.8% (significantly greater than 0, p b 0.0001, t = 4.17, df = 19). Commission error rates for individual participants ranged from 0.0% to 10.0%. Commission error rates for neutral NoGo trials (3.0 ± 3.4%) and aversive NoGo trials (4.0 ± 5.3%) did not differ significantly (p = 0.36, t = 0.94, df= 19). 18 participants made no omission errors on Go trials, while two participants had omission error rates of 4.3% and 0.6%. Response latencies (mean ±between-subjects standard deviation) were: correct neutral Go trials 624±136 ms, correct aversive Go trials 640±150 ms, commission error neutral NoGo trials 557±132 ms, commission error aversive NoGo trials 600±277 ms. Mixed effects ANOVA found a significant main effect on latency with error NoGo trial latencies being shorter than correct Go trial latencies (p=0.002, F= 9.33, effect df=1, residual df=3212). The main effect on latency for neutral vs. aversive distractors was not significant (p=0.21, F=1.56, effect df=1, residual df=3212), nor was there a significant interaction effect (p=0.47, F=0.52, df =1,3212). Participants rated IAPS distractor picture valences lower for aversive distractor images (3.19 ±0.62) compared to neutral distractor images (5.30± 0.23). This main effect was significant (mixed effects ANOVA, p b 0.0000000001, F = 183.78, df= 1,19). There was no significant main effect on valence ratings for Go vs. NoGo trials (p = 0.59, F = 0.31, df= 1,19), nor a significant interaction (p = 0.46, F = 0.56, df= 1,19). Arousal ratings were significantly higher for aversive distractor trials (4.92 ±1.17) compared to neutral distractor trials (2.07 ± 0.91). Main effect of aversive vs. neutral distractors on arousal ratings was significant (mixed effects ANOVA, p = 0.000000001, F = 143.06, df= 1,19). Main effect on arousal for Go vs. NoGo trials was not significant (p = 0.60, F= 0.28, df= 1,19), nor was the interaction effect significant (p = 0.26, F = 1.32, df= 1,19). fMRI results There was greater NoGo vs. Go activation (response inhibition activity) bilaterally in the inferior frontal gyrus (IFG)/operculum (Figs. 3 and 4, Table 1). This IFG region corresponded to ventro-lateral prefrontal cortex (vlPFC) as discussed in Mitchell (2011). Right and left IFG also exhibited significantly greater activation for aversive vs. neutral distractor trials, for neutral NoGo vs. neutral Go trials, for aversive Go vs. neutral Go trials, and for aversive NoGo vs. aversive Go trials (see Fig. 4 right panels and Table 1). Bilateral IFG also exhibited larger activation for aversive NoGo vs. neutral NoGo trials (significant in right IFG at p = 0.003, approaching significance in the left IFG at p = 0.08, see Table 1). Importantly, right and left IFG did not exhibit significant interaction effects between impulse control (NoGo vs. Go) and emotional distractor context (aversive vs. neutral) (interaction contrast: right IFG p = 0.55, t= 0.61, df=19; left IFG p = 0.39, t = -0.87, df= 19; see Table 1). The left IFG cluster was much smaller than the right IFG cluster

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

441

Fig. 5. Main effects statistical contrast map for aversive–neutral distractor images, collapsed across NoGo and Go trials. Neurological convention used. Red/yellow regions exhibited higher activation for aversive distractors. Numbers above and left of each slice denote Z coordinates in MNI space in mm. All results p b 0.05 corrected for multiple comparisons (between subjects df = 19).

(right IFG 8100 mm3; left IFG 1512 mm3). The left IFG exhibited activation magnitudes very similar to the right IFG (see Fig. 4 right panels and Table 1). A direct comparison of the NoGo–Go contrast amplitudes for right and left IFG did not reveal any significant differences (p = 0.58, paired-samples t = 0.56, df = 19). There was also greater NoGo vs. Go activation in the right anterior superior frontal sulcus, bilateral inferior frontal sulcus, orbitofrontal cortex, bilateral intraparietal sulcus extending into the transverse temporal sulcus, right dorsal parieto-occipital sulcus, bilateral middle temporal gyrus and angular gyrus, right inferior temporal cortex, and left lateral occipital sulcus (Fig. 3, Table 1). We found greater Go vs. NoGo activation (response execution activity) in the left motor and somatosensory cortex (reflecting right hand button press responses unique to Go trials), bilateral insula, anterior cingulate gyrus, and left putamen/globus pallidus (see Fig. 3 and Table 1). These results are consistent with previous event-related fMRI studies using the Go/NoGo task (Fassbender et al., 2004; Garavan

et al., 1999, 2002; Kelly et al., 2004; Mostofsky et al., 2003; Rubia et al., 2005; Wager et al., 2005; Watanabe et al., 2002). There was greater activation for aversive vs. neutral distractor pictures (aversive emotional context activity) in numerous regions (see Fig. 5 and Table 1) including bilateral inferior frontal gyrus/operculum, bilateral orbitofrontal cortex, bilateral insula, bilateral medial temporal cortex/ amygdala (see Fig. 6), bilateral middle temporal gyrus/angular gyrus, and several regions in the anterior and posterior cingulate cortex as well as in the thalamus and midbrain. These results are consistent with the fMRI literature on emotional processing with IAPS pictures (Bermpohl et al., 2006; Hayes and Northoff, 2011; Irwin et al., 1996; Meseguer et al., 2007). To investigate the interaction of impulse control and emotional context, we examined modulation of NoGo vs. Go trial activation by the aversive vs. neutral distractor images. Specifically, we used the interaction contrast (aversive NoGo–aversive Go)–(neutral NoGo–neutral Go) (Figs. 7, 8, 9 and Table 1). There was a significant bilateral region in the

442

M.R.G. Brown et al. / NeuroImage 63 (2012) 434–446

Aversive - Neutral Distractors Contrast

Right Amygdala Timecourses

posterior middle temporal gyrus and angular gyrus (Fig. 8 top two panels). This region exhibited similar BOLD activity for the neutral Go and neutral NoGo conditions, significantly larger activity for aversive Go trials, and significantly larger activity still for aversive NoGo trials (see Fig. 8 upper right panel, Table 1). The interaction contrast revealed a significant cluster in the right frontal eyefield, in the anterior bank of the precentral sulcus where it intersects with the superior frontal sulcus (see Fig. 8 bottom two panels). There was also significant interaction contrast in the right precentral, central and postcentral sulci, in the left dorsal precentral and postcentral gyri, and in bilateral cingulate gyrus, right insula, right caudate and putamen, and left caudate (Figs. 7, 9, Table 1).

impulse control and emotion processing in IFG. The “interference hypothesis” (Fig. 1 left panel) stated that response inhibition and emotion processing might interfere with each other causing reduced fMRI activation in IFG—that is, reduced activation for aversive NoGo trials compared to either neutral NoGo or aversive Go trials. The “additive hypothesis” (Fig. 1 middle panel) stated that response inhibitionand emotion-related processing in IFG might operate in parallel and predicted that activation for impulse control in an aversive emotional context (aversive NoGo–neutral Go) should be approximately the sum of response inhibition activation (neutral NoGo–neutral Go) and emotional distractor activation (aversive Go–neutral Go), with no significant interaction contrast effect. The “enhancement hypothesis” (Fig. 1 right panel) stated that response inhibition and emotional processing in IFG may enhance or mutually reinforce each other. This hypothesis predicted that activation for impulse control in an aversive emotional context (aversive NoGo–neutral Go) should be greater than the sum of response inhibition activation (neutral NoGo–neutral Go) and emotional distractor activation (aversive Go–neutral Go), with a significant interaction contrast effect. Our results support the additive hypothesis rather than the interference or enhancement hypotheses. It is possible that emotional context may affect impulse control processes by modulating them rather than interfering with them. We found significant clusters of NoGo vs. Go activation in both the left and right IFG. Previous studies have found a partial right side lateralization of inhibition-related activation in IFG (see Aron et al., 2004a). Consistent with the laterality pattern, our right IFG cluster (8100 mm3) was substantially larger than the left IFG cluster (1512 mm3). However, the left and right IFG both exhibited similar response inhibition (NoGo–Go) contrast amplitudes. This observation is consistent with other studies that found left IFG activation with the Go/NoGo task (Konishi et al., 1999; Menon et al., 2001). It is possible that the left IFG region, being smaller, may simply be harder to detect using fMRI, particularly when a cluster volume threshold is used to correct for multiple comparisons.

Discussion

Interaction of Go/NoGo and emotion processing activity

Emotional situations can impact sensory processing and impulse control with important consequences for decision making. This is relevant for high risk behaviors like drug use or physical fighting which can be caused by impulsive decision making in emotional situations. To investigate the interaction of behavioral control and emotional context, we performed fMRI brain scanning using an event-related Go/NoGo task with emotional distractor images. Ours is the first event-related fMRI study to examine the effects of task-irrelevant emotional stimulus distractors on response inhibition processing where emotional context was modulated independently of response inhibition.

We found evidence for interaction between Go/NoGo processes and emotional processing in a bilateral region in the posterior middle temporal gyrus and angular gyrus. Previous fMRI Go/NoGo studies (without any emotional component) have found task-related differences in or close to this region (Asahi et al., 2004; de Zubicaray et al., 2000; Fassbender et al., 2004; Garavan et al., 1999, 2002; Horn et al., 2003; Kelly et al., 2004; Konishi et al., 1999; Maguire et al., 2003; Menon et al., 2001; Mostofsky et al., 2003; Rubia et al., 2005; Wager et al., 2005; Watanabe et al., 2002). The angular gyrus has been implicated in many different functions including visual attention, resolution of conflict in stimulus- or response-related processing, semantic processing, number processing, default mode (resting state) processing, memory retrieval, and social cognition (Seghier, 2012). Inferior parietal lobule, extending into the angular gyrus in many studies, is thought to be involved in visual attention (see Corbetta, 1998; Corbetta and Shulman, 2002; Seghier, 2012; Singh-Curry and Husain, 2009). The emotional Go/NoGo task required participants to attend to the Go/NoGo stimulus (square vs. circle) while ignoring the distractor pictures. The posterior middle temporal gyrus and the angular gyrus exhibited larger activation for aversive distractor trials compared to neutral distractor trials. This result may reflect increased attention demands caused by aversive distractor images. A meta-analysis by Nee et al. (2007) of tasks requiring resolution of stimulus conflict and/or response conflict indicates that the angular gyrus may be involved in conflict resolution in the Go/NoGo task (see also Seghier, 2012). We observed an interaction effect in the posterior middle temporal gyrus and angular gyrus, with a significant NoGo vs. Go activation difference in trials with aversive distractors but not in trials with neutral distractors. This interaction result may reflect the interaction of emotional

0.2 Neutral Go Aversive Go Neutral NoGo Aversive NoGo

BOLD (%)

0.15 0.1 0.05 0 −0.05

0

5

10

15

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Time (s) Fig. 6. Left: Statistical t-map for distractor picture valence contrast (aversive Go+aversive NoGo)–(neutral Go+neutral NoGo). Red/yellow regions showed greater activation for aversive distractor pictures. All results pb 0.05 corrected for multiple comparisons. Neurological convention used. Color bar indicates scaling for T values. Number in upper left denotes the slice's Z coordinate in MNI space in mm. Right: Deconvolved timecourses for the right amygdala and surrounding cortex (region outlined in green on left panel) for four trial types.

Inferior frontal gyrus The inferior frontal gyrus (IFG) is important for behavioral impulse control (a.k.a. response inhibition) (see Aron et al., 2004b, 2007; Mitchell, 2011; Nee et al., 2007; Wager et al., 2005). It is also implicated in attention and detection of task-relevant stimuli (see Hampshire et al., 2010; Mitchell, 2011) as well as in processing emotional stimuli and inhibiting or otherwise modulating emotional responses (see Dolcos et al., 2011; Mitchell, 2011). Poor impulse control can predispose one to potentially dangerous high risk behavior (see Arnett, 1992; Jessor, 1991). Executive control systems (including impulse control circuits) and emotion systems have been suggested to compete and mutually suppress each other (Drevets and Raichle, 1998; Mayberg et al., 1999). One possible explanation of poor impulse control in emotional situations is that emotional stimuli and context might compete with and interfere with response inhibition processes in the brain, resulting in impaired impulse control. We tested three different hypotheses on the interaction of

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Fig. 7. Interaction contrast map (aversive NoGo–aversive Go)–(neutral NoGo–neutral Go). Neurological convention used. Numbers above and left of each slice denote Z coordinates in MNI space in mm. All results p b 0.05 corrected for multiple comparisons (between subjects df = 19).

stimulus-driven attention processes with Go/NoGo conflict resolution processes in this region. We found a Go/NoGo by emotional distractor interaction in the right frontal eye field as well as greater aversive vs. neutral distractor activation. The frontal eye fields are involved in eye movement control and visual attention (see Munoz and Everling, 2004). The aversive distractor pictures may have evoked more processing related to attention and exploratory saccadic eye movements compared to the neutral distractors (though we did not have eye tracking during fMRI scanning to test for differences in eye movements). We attribute the interaction result in the right frontal eye field to modulation of attention and eye movement processes by response requirement. High risk behavior The interaction of behavioral impulse control and emotional processing is important in high risk decision making. Several studies have examined emotional Go/NoGo fMRI patterns in various groups prone to high risk behavior, including adolescents (Hare et al., 2008), borderline personality disorder patients (Silbersweig et al.,

2007), panic disorder patients (Beutel et al., 2010), bipolar disorder patients (Wessa et al., 2007), and individuals with a history of developmental deprivation (Tottenham et al., 2011). These studies found differences in activation between high risk groups and controls in the inferior frontal gyrus, posterior middle temporal gyrus, and/or angular gyrus related to response inhibition, emotion processing, or the interaction of response inhibition and emotion processing. High risk behavior has been explained in terms of an individual's impulsivity, or tendency toward poor control of behavior and emotions (see Arnett, 1992; Jessor, 1991). The Go/NoGo task recruits impulse control in the specific form of inhibiting prepotent (“trained in”) button press responses. Asahi et al. (2004) have shown that activation in the right dorsolateral prefrontal cortex recruited by response inhibition in the NoGo task is inversely correlated with individual impulsivity. Greater impulsiveness has also been correlated with lesser gray matter volume in frontal regions associated with inhibition and flexible control of behavior, including orbitofrontal cortex, middle frontal gyrus, and superior frontal gyrus (Schilling et al., 2011, 2012). The current study establishes the utility of our emotional Go/ NoGo task for investigating modulation of impulse control by task-

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irrelevant emotional context in regions such as the inferior frontal gyrus. In future studies, it would be instructive to apply this emotional Go/NoGo task to compare populations prone to impulsive, high risk behaviors with low-risk control groups. We would expect to see reduced inferior frontal gyrus activation related to response inhibition and emotion regulation in high risk vs. low risk participant groups.

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We investigated the interaction of response inhibition with emotional context using fMRI and a Go/NoGo task with emotional distractor pictures. Response inhibition activity and emotion processing activity in the inferior frontal gyrus combined additively. We found interaction effects in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, as well as other regions. We attribute these results to interaction between emotion-related processing, including attention processes, and Go/NoGo-related conflict resolution processes. These regions may be involved in mediating changes in impulse control caused by emotional situations. In this study, we used neutral and aversive emotional stimuli. Approach processes and avoidance processes may interact differently with response inhibition, and it would be instructive to explore this issue using an emotional Go/NoGo study that included positive as well as neutral and aversive emotional distractors.

Time (s) Fig. 8. Left panels: Slices from statistical t-map for interaction contrast (aversive NoGo– aversive Go)–(neutral NoGo–neutral Go). All results p b 0.05 corrected for multiple comparisons. Neurological convention used. Color bars indicate scaling for T values. Numbers in upper left denote each slice's Z coordinate in MNI space in mm. Right panels: Deconvolved time courses for four trials types for regions outlined in green on left panels. Upper-right panel: right posterior middle temporal gyrus/angular gyrus (pMTG/AG). Lower-right panel: right frontal eye field (FEF) at the junction of the superior frontal and precentral sulci.

R Frontal Eye Fields

This work was supported by the Norlien Foundation, the Women and Children's Health Research Institute, Alberta Innovates—Health Solutions, the Alberta Mental Health Board, Alberta Health Services, the University of Alberta Hospital Foundation, and the University of Alberta. Part of this material was previously presented by the authors in abstract 198.7 at the 2009 Society for Neuroscience Annual Meeting

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Fig. 9. Mean BOLD amplitudes and standard deviations for four trial types for all regions of interest revealed in the interaction statistical contrast map (see Fig. 7 and Table 1). NG = neutral Go trial. AG = aversive Go trial. NN = neutral NoGo trial. AN = aversive NoGo trial. SFG = superior frontal gyrus. pMTG/AG = posterior middle temporal gyrus/angular gyrus. PreCG = precentral gyrus. PostCG = postcentral gyrus.

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in Chicago, IL, USA and as abstract 3997 at the 2011 Organization for Human Brain Mapping in Montreal, QC, Canada. The work described here was undertaken under the auspices of the Child/Adolescent At Risk Population Imaging, neuropsychology, and population health team (CARPI), of which the authors are members.

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