Journal of Traumatic Stress

February 2016, 29, 33–40

Intimate Partner Violence PTSD and Neural Correlates of Inhibition

Robin L. Aupperle,1,2 Ashley N. Stillman,1,3 Alan N. Simmons,4,5,6,7 Taru Flagan,7 Carolyn B. Allard,4,6,7,8
Steven R. Thorp,4,6,7,8 Sonya B. Norman,6,7,8 Martin P. Paulus,1,5,6,7 and Murray B. Stein5,9
1
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
2
Department of Community Medicine, University of Tulsa, Tulsa, Oklahoma, USA
3
Department of Psychology, University of Tulsa, Tulsa, Oklahoma, USA
4
Research Service, VA San Diego Healthcare System, San Diego, California, USA
5
Psychiatry Service, VA San Diego Healthcare System, San Diego, California, USA
6
Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, California, USA
7
Department of Psychiatry, University of California-San Diego, San Diego, California, USA
8
Psychology Service, VA San Diego Healthcare System, San Diego, California, USA
9
Family Medicine and Public Health, University of California-San Diego, San Diego, California, USA

Posttraumatic stress disorder (PTSD) has been linked to deficits in response inhibition, and neuroimaging research suggests this may
be due to differences in prefrontal cortex recruitment. The current study examined relationships between PTSD from intimate partner
violence (IPV) and neural responses during inhibition. There were 10 women with PTSD from IPV and 12 female control subjects without
trauma history who completed the stop signal task during functional magnetic resonance imaging. Linear mixed models were used to
investigate group differences in activation (stop–nonstop and hard–easy trials). Those with PTSD exhibited greater differential activation to
stop–nonstop trials in the right dorsolateral prefrontal cortex and the anterior insula and less differential activation in several default mode
regions (d = 1.12–1.22). Subjects with PTSD exhibited less differential activation to hard–easy trials in the lateral frontal and the anterior
insula regions (driven by less activation to hard trials) and several default mode regions (i.e., medial prefrontal cortex, posterior cingulate;
driven by greater activation to easy trials; d = 1.23–1.76). PTSD was associated with difficulties disengaging default mode regions during
cognitive tasks with relatively low cognitive demand, as well as difficulties modulating executive control and salience processing regions
with increasing cognitive demand. Together, these results suggest that PTSD may relate to decreased neural flexibility during inhibition.

Neuropsychological research provides evidence for subtle
deficits in executive functions, including response inhibition,
for individuals with posttraumatic stress disorder (PTSD;
Aupperle, Melrose, Stein, & Paulus, 2012; Polak, Witteveen,
Reitsma, & Olff, 2012). Executive functions are considered
important for supporting optimal social and occupational func-
tioning and likely contribute to emotion regulation (Barkley &
This study was funded by the Department of Veterans Affairs (Merit Award
to MBS). Dr. Thorp is funded by a VA Career Development Award and a
Department of Defense grant. Drs. Paulus, Simmons, and Norman are funded
by VA Merit Awards.
We would like to acknowledge the contributions of Michelle Behrooznia,
Shadha Cissell, Erin Grimes, Kelly Hughes-Berardi, Lindsay Reinhardt, and
Sarah Sullivan, towards coordinating the study, recruiting subjects, and/or
collecting behavioral and fMRI data. We would also like to acknowledge the
contribution of Greg Fonzo, in creating the anatomical masks used for fMRI
region-of-interest analyses.
Correspondence concerning this article should be addressed to Robin L.
Aupperle, Laureate Institute for Brain Research, 6655 Yale Avenue, Tulsa,
OK 74136. E-mail: raupperle@laureateinstitute.org
Copyright  C 2016 International Society for Traumatic Stress Studies. View
Murphy, 2010; Zelazo & Cunningham, 2007). Further de-
lineating these cognitive deficits and their associated neural
underpinnings is therefore important for understanding the
development and treatment of PTSD.
Response inhibition refers to the suppression of automatic,
but no longer required, responses to a situation to respond in
a goal-driven manner and can be assessed using a variety of
tasks (e.g., color-word Stroop, go–no go, stop signal; Chambers,
Garavan, & Bellgrove, 2009). Decreased inhibitory function has
been repeatedly identified for those with PTSD and observed
using tasks involving either emotional or nonemotional stimuli
(Aupperle et al., 2012; Bressan et al., 2009; Casada & Roache,
2005; Falconer et al., 2008; Koso & Hansen, 2006; Lagarde,
Doyon, & Brunet, 2010; Leskin & White, 2007; Litz et al., 1996;
Shucard, McCabe, & Szymanski, 2008). Underlying inhibitory
dysfunctions could be important not only for maintaining opti-
mal cognitive functioning, but also for inhibiting maladaptive
responses after a trauma (e.g., hypervigilance, intrusive mem-
ories and thoughts, or associated anger or high-risk behaviors;
Aupperle et al., 2012).

this article online at wileyonlinelibrary.com Tasks involving response inhibition rely on activation within
DOI: 10.1002/jts.22068 inferior and middle frontal gyri (i.e., dorsolateral prefrontal

33
34
cortex [PFC]), which are thought to play a role in inhibiting
responses, as well as the medial PFC (i.e., anterior cingulate
cortex [ACC]), thought to play more of a role in monitoring
responses and outcomes (Chambers et al., 2009; Ridderinkhof,
van den Wildenberg, Segalowitz, & Carter, 2004; Verbruggen
& Logan, 2008). Neuroimaging studies in PTSD have primarily
focused on symptom provocation or responses to trauma-related
or emotional stimuli. In general, results from these studies
suggest increased activation within amygdala and insula and
hypoactivation of prefrontal regions, including ACC, medial
PFC, and lateral PFC (Etkin & Wager, 2007; Francati, Ver-
metten, & Bremner, 2007; Liberzon & Sripada, 2008; Shin &
Liberzon, 2010; Simmons & Matthews, 2011), though there
have been some inconsistencies regarding the directionality of
these effects (Etkin & Wager, 2007). A small collection of re-
cent studies has investigated how PTSD relates to differences
in brain activation during response inhibition to nonemotional
stimuli. Many have identified prefrontal dysfunction, though
the directionality of findings is inconsistent. Attenuated acti-
vation has been reported in regions such as the inferior frontal
gyrus, and medial and lateral PFC, the degree of which often re-
lates to inhibitory performance (i.e., rate of commission errors;
Carrion, Garrett, Menon, Weems, & Reiss, 2008; Falconer et al.,
2008; Moores et al., 2008). Disruptions in network connectivity
within right frontal regions (including both lateral and medial
aspects) have also been found to relate to commission errors on
the go–no-go task in PTSD (Sadeh et al., 2015). PTSD how-
ever, has also been associated with increased recruitment of
PFC regions, including ACC, during inhibition tasks (Carrion
et al., 2008; Shin et al., 2011). More recent research also sug-
gests that the degree of activation within these frontal networks
during inhibition may predict response to cognitive–behavioral
therapy for PTSD, demonstrating the potential clinical impor-
tance of understanding inhibitory functions in this population
(Falconer, Allen, Felmingham, Williams, & Bryant, 2013).
The current study sought to add to the current literature re-
lated to inhibition and PTSD by examining whether women
with PTSD from intimate partner violence (IPV) also show in-
hibitory processing deficits (as most previous research has been
with other trauma populations) and whether these deficits are
associated with performance during neuropsychological assess-
ment of response inhibition (i.e., using the color-word task). We
hypothesized that those with PTSD (compared to nontrauma-
exposed controls) would exhibit attenuated recruitment within
the ACC, inferior frontal gyrus, and dorsolateral PFC during
inhibition (as measured using the stop signal task) and that the
level of attenuation would relate to dysfunction on neuropsy-
chological testing.
Method
Participants
There were 10 women with PTSD from IPV (mean age =
34.60 years; SD = 9.40) and 12 female control subjects
(mean age = 35.25 years; SD = 6.44) with no trauma his-
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
Aupperle et al.
tory who completed clinical and neuropsychological assess-
ment, and the functional magnetic resonance imaging (fMRI)
stop signal task. Neuropsychological data and data from other
neuroimaging tasks collected from this same cohort are pub-
lished elsewhere (Fonzo et al., 2010; Twamley et al., 2009).
The groups did not differ on age, t(20) = 0.19, p = .850, but the
PTSD group had fewer years of education, PTSD M = 13.60;
SD = 1.58; control subjects M = 15.83, SD = 1.27; t(20) =
3.69, p = .001. Education was therefore used as a covariate in
the group analyses.
PTSD diagnosis according to the Diagnostic and Statisti-
cal Manual of Mental Disorders (4th ed., DSM-IV; American
Psychiatric Association, 1994) was verified with the Clinician-
Administered PTSD Scale (Blake et al., 1995). Control subjects
did not meet criteria for any mental health disorder. Exclusion
criteria included substance abuse in the past year; history of
more than 5 years of substance abuse; use of psychotropic medi-
cations within 4 weeks, history of bipolar disorder, schizophre-
nia, attention deficit disorder, or learning disability; loss of
consciousness that was ࣙ10 min in duration; neurological ill-
ness; irremovable ferromagnetic material; pregnancy; or claus-
trophobia. Of the 10 women with PTSD from IPV, 4 women
also met criteria for PTSD related to other traumas (i.e., child-
hood trauma), but administration of both interview and self-
report PTSD measures were anchored specifically to the IPV
trauma. There were two women with PTSD who reported loss
of consciousness after blunt head trauma (that was < 10 min)
occurring during adulthood (at least 1 month prior to study
enrollment); another two women (one PTSD, one control sub-
ject) reported loss of consciousness < 10 min occurring in
childhood. The University of California San Diego Human Re-
search Protections Program and the Veterans Affairs San Diego
Healthcare System Research and Development Office approved
the protocol. Written informed consent was obtained from all
subjects.
Measures
The PTSD Checklist (PCL) is a 17-item self-report mea-
sure, which was utilized to quantify severity of PTSD
symptoms (total score). This measure has been reported to
have an α reliability coefficient of .97 in previous research
(Blanchard, Jones-Alexander, Buckley, & Forneris, 1996;
Weathers, Huska, & Keane, 1991). The Clinician-Administered
PTSD Scale (CAPS) is a 30-item semistructured diagnostic in-
terview, which was used to confirm PTSD diagnosis and to pro-
vide another estimate of symptom severity (CAPS frequency
+ intensity total score [past month]). The CAPS has been re-
ported to have an α coefficient of .94 in previous research
(Blake et al., 1995). The Delis-Kaplan Executive Function Sys-
tem Color-Word Test (Delis, Kaplan, & Kramer, 2001) is a
standard neuropsychological assessment that was administered
to assess for executive function performance. Age-scaled scores
were calculated for the time to complete each of the four sub-
tests, including color naming, word reading, inhibition, and
 PTSD and Neural Correlates of Inhibition
inhibition/switching conditions. The color naming condition
involves naming a sequence of color patches; the word reading
condition involves reading words that denote colors printed in
black ink; the inhibition condition involves naming the ink color
in which color words are printed; and inhibition-switching in-
volves switching back and forth between naming the ink colors
and reading the words. All measures were administered during
one in-person session within 6 weeks prior to fMRI scanning.
fMRI Procedure
The stop signal task was administered as described elsewhere
(Matthews, Simmons, Arce, & Paulus, 2005). Briefly, subjects
pressed left and right buttons for X and O “go” signals presented
on the computer screen, but were to not press any button when
they heard a “stop” signal tone. Each trial lasted 1,300 ms or
until a response, with 200-ms interstimulus intervals. Each of
six blocks included 48 trials (12 stop, 36 nonstop, counterbal-
anced), with each block separated by 12 s of fixation. Total task
time was 8 min 32 s. Average response latency (ARL) was cal-
culated from prescan practice (which consisted of four blocks
of 48 trials each) to construct individualized hard, moderate,
and easy trials for the scan (as described below). Due to equip-
ment failure, behavioral responses during the scan were not
recorded. Prescan ARL and color-word performance, however,
were available for analyses.
One fMRI run sensitive to blood oxygenation level-
dependent contrast was collected concurrently with completion
of the stop signal task using a Signa EXCITE (GE Health-
care, Milwaukee, WI) 3.0-T scanner (T2* weighted echo pla-
nar imaging, repetition time = 2,000 ms, echo time = 32
ms, field of view = 230 mm, 64 × 64 matrix, 30 2.6-mm
axial slices, 1.4-mm gap, 256 scans, 512 s). A T1-weighted
image (magnetization-prepared rapid gradient-echo, relaxation
time = 8.0 ms, echo time = 4.0 ms, flip angle = 12°, 172 sagit-
tal slices, field of view = 250 × 250 mm, ࣈ1-mm3 voxels) was
also obtained prior to the fMRI run.
Data Analysis
As noted above, the stop signal task behavioral responses dur-
ing the scan were not recorded due to equipment failure. There
were no other missing data, however, from the study dataset.
Analyses of covariance (education as covariate) were used to
examine group differences in (a) ARL on the stop signal task
prescan practice (nonstop trials), and (b) Delis-Kaplan Exec-
utive Function System Color-Word Test (Delis et al., 2001)
performance, including scaled scores for color naming, word
reading, inhibition, and inhibition/switching conditions. Spear-
man’s ρ correlations (two-tailed) were used to investigate the
relationship between symptom severity (indexed via the CAPS
frequency + intensity total score [past month] and PCL total
score), nonstop signal ARL, and color-word test performance.
Spearman’s ρ correlations were used for correlational analyses
due to nonnormal distributions of some variables of interest.
For the subjects with PTSD, this included color-word test color
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
35
naming, with skewness of −1.92 (SD = .69) and kurtosis of
4.44 (standard error [SE] = 1.33), and color-word test inhi-
bition, with skewness of −1.29 (SE = .69) and kurtosis of
2.23 (SE = 1.33). For the control subjects, this included color-
word test inhibition/switching, with a kurtosis of 4.21 (SE =
1.23).
The fMRI data were analyzed using the analysis of func-
tional neuroimages (Cox, 1996) and the R statistical package
(R Core Team, 2014). Functional images were aligned to high-
resolution anatomical images. Time series were interpolated to
correct for nonsimultaneous slice acquisition and motion cor-
rected. Multiple regression models included regressors for the
following: (a) nonstop trials (with no stop signal), (b) hard stop
trials (stop signal delivered at the individual subject’s ARL or
100 ms before their ARL [ARL −100 ms]), (c) medium stop tri-
als (ARL − 200 ms; ARL − 300 ms), (d) easy stop trials (ARL
− 400 ms; ARL − 500 ms), (e) residual motion (roll, pitch, and
yaw), and (f) signal drifts (baseline and linear trends). General
linear tests were computed for (a) hard–easy and (b) all stop–
nonstop trials. The percentage of signal change was calculated
by dividing the regressor of interest by the baseline. Data were
spatially blurred (4-mm full width at half maximum), resam-
pled to 4 mm3 , and normalized to Talairach space (Talairach &
Tournoux, 1988).
Linear mixed effects models were used to identify group ef-
fects on hard–easy and stop–nonstop percent signal change with
education as a covariate and subject as a random effect. Anal-
yses were conducted voxel-wise for a priori regions of interest
that have been found repeatedly to relate to PTSD diagnosis or
symptoms (the amygdala, insula, and cingulate) or to executive
functioning and response inhibition (the inferior and middle
frontal gyri), as discussed in the introduction. Region of inter-
est mask construction has been described elsewhere (Aupperle
et al., 2013). Results were considered significant at p < .05; with
the Monte Carlo method used to correct for mutiple compar-
isons, resulting in a minimum cluster extent of 832 mm3 for the
whole brain, 384 mm3 for the inferior or middle frontal gyri, or
the cingulate, 192 mm3 for the amygdala, and 320 mm3 for the
insula. Percent signal change was extracted from each cluster
and Spearman’s correlations (two-tailed) used to explore re-
lationships with symptom severity and inhibition performance
for the PTSD group (due to limited samples size, correlations
were constrained to clusters within regions of interest). For ex-
ploratory and descriptive purposes, we report correlations that
meet p < .05. All relevant effect sizes are reported to meet
standard reporting guidelines. It is recognized, however, that
effect sizes from fMRI results may be inflated (Yarkoni, 2009).
Results
There were no group differences on prescan ARL, F(1, 18) =
0.09, Cohen’s d = 0.1, p = .774. When adjusting for education,
the PTSD group performed worse on color-word reading,
F(1, 19) = 4.51, Cohen’s d = 0.91, p = .047. Differences in
36 Aupperle et al.

Table 1
All Results From Whole Brain Analyses of Group Effects on Stop Versus NonStop Trials of the Stop Signal Task
Coordinates
Side BA Region Cluster size x y z d Mean F
PTSD > Control
R 9 Middle frontal (dorsolateral PFC) 1088 44 15 32 1.01 5.60
R 22,13 Superior temporal/insula 832 45 2 −6 1.10 6.50
Control > PTSD
R 40 Inferior parietala 896 39 −48 56 1.09 6.52
L 10 Superior medial PFCb 2368 −5 61 7 1.13 7.01
R 24 Rostral ACCb 896 1 23 16 1.12 6.68
R Putamenb 896 15 7 −1 1.03 5.77
L Caudate and putamenb 832 −9 12 1 1.04 5.93
R 39 Middle temporalb 1728 44 −59 15 1.23 8.26
R Parahippocampal gyrusb 1088 27 −23 −5 1.03 5.81
L 40 Postcentral gyrusb 5248 −34 −39 50 1.23 8.29
R 7 Precuneusb 1728 25 −43 39 1.18 7.57
L 7 Precuneusb 832 −3 −52 55 1.18 7.59
L 4 Paracentral cortexb 896 −6 −39 66 1.17 7.46
L 17 Middle occipitalb 3136 −19 −82 10 1.11 6.74
R 19 Lingual gyrus. middle occipitalb 1088 29 −74 −2 1.12 6.85
L Cerebellar tonsilb 2816 −25 −66 −33 1.05 6.07
R Superior cerebellumb 2048 14 −63 −36 1.00 5.48
Note. Results are reported for a sample of 22 (12 control; 10 PTSD). Center of mass Talairach coordinates (x, y, z) are based on Talairach Daemon software (Lancaster
et al., 2000). Cluster size is shown as mm3 . Effect sizes are Cohen’s d. BA = Brodmann area; PFC = prefrontal cortex; ACC = anterior cingulate cortex.
a Regions in which subjects with PTSD exhibited less activation than control subjects to Stop trials. b Regions in which subjects with PTSD exhibited greater activation

than control subjects to nonstop trials.

inhibition/switching performance, however, were not signifi-
cant, F(1, 19) = 4.23, Cohen’s d = 0.88, p = .054). There were
no group differences on color naming, F(1, 19) = 1.31, Cohen’s
d = 0.49, p = .266) or inhibition, F(1, 19) = 1.64, Cohen’s
d = 0.55, p = .216). PTSD group PCL and CAPS scores did
not correlate with ARL (PCL: rs = −.47, p = .284; CAPS:
rs = −.39, p = .383) or color-word test performance, including
color naming (PCL: rs = −.20, p = .571; CAPS: rs = −.27,
p = .454), word reading (PCL: rs = .50, p = .144; CAPS: rs =
.21, p = .557), inhibition (PCL: rs = .20, p = .578; CAPS: rs
= .01, p = .986), and inhibition/switching (PCL: rs = .45, p =
.192; CAPS: rs = −.02, p = .960). ARL also did not correlate
with color-word performance (color naming: rs = .69, p =
.085; word reading: rs = .07, p = .876; inhibition: rs = .19,
p = .679; inhibition/switching: rs = −.05, p = .908).
For region-of-interest analyses, those with PTSD exhibited
greater stop–nonstop activation than control subjects in the right
dorsolateral PFC, the Brodmann area (BA) 9; x, y, z = 44, 15,
32; F(1, 19) = 5.60; Cohen’s d = 1.01; 1,088 mm3 , the right
anterior insula, BA 13; x, y, z = 46, 1,−3; F(1, 19) = 6.62;
Cohen’s d = 1.10; 384 mm3 , and the left posterior insula, BA
13; x, y, z = −37, −11, 12; F(1, 19) = 6.66; Cohen’s d = 1.11;
320 mm3 , driven by those with PTSD exhibiting less activa-
tion to nonstop trials. In addition, those with PTSD exhibited
less differential left inferior frontal activation, BA 46; x, y, z
= −43, 40, 5; F(1, 19) = 5.28; Cohen’s d = 0.98; 384 mm3 ,
driven by greater activation to nonstop trials. Whole-brain anal-
yses confirmed the dorsolateral PFC and anterior insula clusters
(but not the inferior frontal gyrus or posterior insula clusters)
and revealed less differential activation within several default
mode network regions (i.e., precuneus, medial PFC; Table 1),
driven by PTSD relating to greater activation to nonstop trials
(Figure 1). Results from voxel-wise, whole-brain analyses are
included in Table 1.
For region-of-interest analyses, those with PTSD exhibited
less hard–easy activation than control subjects within the right
rostral ACC, BA 32; x, y, z = 3, 43, 8; F(1, 19) = 7.01; Co-
hen’s d = 1.13; 960 mm3 , the left inferior frontal gyrus left:
BA 47; x, y, z = −24, 28, −10; F(1, 19) = 7.51; Cohen’s d
= 1.17; 704 mm3 ; and the lateral middle frontal gyrus, BA
10; x, y, z = 37, 57, 9; F(1, 19) = 7.66; Cohen’s d =1.19;
704 mm3 . In addition, those with PTSD exhibited greater hard–
easy activation than control subjects within the right inferior
frontal gyrus right: BA 47; x, y, z = 52, 36, −7; F(1, 19) = 6.44;
Cohen’s d = 1.09; 384 mm3 ; driven by those with PTSD
exhibiting less activation to easy trials. Whole-brain analy-
ses confirmed the left inferior frontal gyrus, the right rostral
ACC, and the lateral middle frontal gyrus clusters (but not
the right inferior frontal gyrus cluster) and revealed less dif-
ferential activation within the anterior insula and the posterior

Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
 PTSD and Neural Correlates of Inhibition 37

Figure 1. Regions in which those with posttraumatic stress disorder (PTSD; n = 10) exhibited reduced hard–easy activation compared to nontrauma-exposed
controls (n = 12). (A) Those with PTSD exhibited reduced hard–easy activation within the left inferior frontal gyrus (BA 11, 47) and the anterior insula, BA 13),
driven by reduced activation to hard trials. (B) Those with PTSD exhibited reduced hard–easy activation within the bilateral rostral anterior cingulate cortex (ACC;
BA 32) and the right posterior cingulate (BA 30), driven by greater activation to easy trials.

cingulate, among others (Table 2). These effects were driven
by those with PTSD showing less inferior frontal/lateral PFC
and insula recruitment to hard trials, and greater default mode
activation (i.e., posterior cingulate, precuneus) to easy trials
(Figure 1).
Greater PCL score related to less hard–easy rostral ACC
activation (rs = −.66, p = .038). The relationship between
PCL score and hard–easy right inferior frontal activation was
nonsignificant (rs = −.61, p = .060), as were all other Spearman
correlations between PTSD symptom severity (CAPS or PCL)
and percent signal change from identified region of interest
clusters (ps > .140). Greater hard–easy right inferior frontal
gyrus activation related to worse performance on color-word
inhibition (rs = −.50, p = .018); relationships between this
cluster and performance on the other color-word measures were
nonsignificant (color naming: rs = −.32, p = .141; reading: rs
= −.39, p = .072; inhibition/switching: rs = −.41, p = .060).
There were no other significant correlations between region-of-
interest cluster percent signal change and ARL or color-word
performance (all ps >.10).
Discussion
Individuals with PTSD exhibited less differential activation
(stop–nonstop; hard–easy) within numerous default mode net-
work regions (i.e., the medial PFC, posterior cingulate, and
precuneus) and the level of medial PFC activation related to
PTSD symptom severity. These findings were driven by those
with PTSD exhibiting greater activation for nonstop and easy-
inhibit trials, respectively. This suggests PTSD may relate to
difficulties downregulating default mode regions during rela-
tively low-level cognitive tasks. In other words, PTSD may
relate to difficulties disengaging from internal- or self-focused
processing to attend to external cognitive demands. This could

Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
38 Aupperle et al.

Table 2
All Results From Whole Brain Analyses of Group Effects on Hard Versus Easy Trials of the Stop Signal Task
Coordinates
Side BA Region Cluster size x y z d Mean F
Control > PTSD
L 11,47 Inferior and middle frontal gyrusa 2240 −22 28 −9 1.26 8.70
L Putamen/anterior insulaa 1408 −20 15 9 1.23 8.27
L 10 Lateral superior frontala 1408 −15 61 22 1.17 7.48
R 10 Lateral superior frontala 960 39 57 9 1.13 7.01
L/R 10,32 Medial PFC, rostral ACCb 2176 7 46 11 1.20 7.83
R 20 Middle temporalb 832 36 −4 −32 1.10 6.65
R 19 Lingual, parahippocampal gyrusb 960 22 −59 −3 1.09 6.45
R 5 Paracentral cortexb 1280 1 −38 65 1.19 7.72
R 30 Posterior cingulateb 1728 8 −55 6 1.21 8.02
R 30 Posterior cingulateb 960 7 −44 22 1.22 8.07
L 7,31 Precuneus, cuneusb 1088 −8 −70 30 1.07 6.22
R 31 Precuneusb 832 16 −62 23 1.11 6.66
L 19 Cerebellum/lingual gyrusb 2560 −16 −55 −7 1.11 6.69
R Cerebellumb 1600 5 −37 −23 1.24 8.36
R Cerebellum (declive)b 1600 41 −74 −20 1.05 6.04
R Cerebellumb 1408 13 −66 −36 1.07 6.22
L Cerebellum (culmen)b 1088 −22 −36 −20 1.22 8.14
Note. Results are reported for a sample of 22 (12 control; 10 PTSD). Center of mass Talairach coordinates (x, y, z) are based on Talairach Daemon software (Lancaster,
et al., 2000). Cluster size is shown as mm3 . Effect sizes are Cohen’s d. BA = Brodmann area; PFC = prefrontal cortex; ACC = anterior cingulate cortex.
a Subjects with PTSD exhibited less activation than control subjects to hard trials. b Subjects with PTSD exhibited more activation than control subjects to easy trials.

be consistent with previous findings of reduced default mode
connectivity during rest (Sripada et al., 2012) and increased
connectivity during a working memory task (Daniels et al.,
2010) in PTSD.
The specific PFC region (and directionality of findings) iden-
tified to relate to PTSD is often inconsistent across studies
(Falconer et al., 2008; Jovanovic et al., 2013; Moores et al.,
2008; Shin et al., 2011). We found PTSD to relate to greater
stop–nonstop activation in the middle frontal gyrus (dorsolat-
eral PFC) and anterior insula. The existence of strong connec-
tions between these regions and dorsal ACC (Liberzon & Sri-
pada, 2008), suggests this may complement reports of greater
dorsal ACC recruitment during the multisource interference
task (Shin et al., 2011). Our findings, however, were driven
primarily by those with PTSD exhibiting reduced activation to
nonstop trials (rather than by more activation to stop trials).
Individuals with PTSD additionally showed less hard–easy ac-
tivation within left inferior frontal gyrus and insula regions,
driven by reduced activation to hard stop trials. Thus, PTSD
may relate to difficulties appropriately modulating activation
in these regions in response to the level of cognitive demand.
Directionality of PFC findings may therefore be inconsistent
between studies due to different levels of task difficulty and/or
the specific contrasts utilized for analyses.
Although stop signal activation was largely unrelated to
color-word performance, there was a relationship between
greater activation within a small right inferior frontal gyrus
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
cluster (BA 47; identified via region-of-interest analyses only)
and worse performance on color-word inhibition. Interestingly,
this cluster was unique from the other findings within the in-
ferior frontal gyrus in that PTSD subjects exhibited greater
hard-easy activation, driven by less activation to easy trials.
Thus, it may be that the ability to appropriately modulate acti-
vation within the right inferior frontal gyrus for tasks involving
relatively low cognitive demand and/or changing levels of cog-
nitive demand may be of importance across various inhibition-
related tasks. This would be consistent with previous research
identifying the inferior frontal gyrus as being particularly im-
portant for inhibitory processes (Chambers et al., 2009). Al-
though the lack of findings in other identified clusters of acti-
vation (i.e., dorsolateral PFC, ACC, left inferior frontal gyrus,
which survived whole-brain analyses) may have been due to
limited power, it also raises the question of whether the vari-
ous inhibition-related tasks (i.e., stop signal, color-word, go–no
go) are probing somewhat different constructs and underlying
neural circuits. Related to this, research has demonstrated that
even small changes to inhibition tasks (such as the go–no go)
can modify the cognitive demands and neural circuits involved
(Simmonds, Pekar, & Mostofsky, 2008). Understanding behav-
ior and neural differences between tasks, or making attempts
to use similar tasks across PTSD studies, could help clarify
discrepancies in the literature.
This study was limited by a relatively small sample size,
cross-sectional design, and lack of behavioral data during the
 PTSD and Neural Correlates of Inhibition
fMRI task. In addition, some of the women included in the
study had experienced previous traumas in addition to IPV.
Given that research has shown previous trauma to be a risk
factor for the development of PTSD (Ozer, Best, Lipsey, &
Weiss, 2003), it would be useful to identify how such trau-
mas (such as childhood trauma) may influence inhibitory
processes. Future research using longitudinal designs, larger
samples, and resting-state connectivity in conjunction with
neuropsychological assessment, would be useful for provid-
ing a more thorough understanding of cognitive functioning in
PTSD.
We showed that PTSD may relate to difficulties disengaging
default mode regions (and associated internally focused pro-
cessing) during inhibition tasks with relatively low cognitive
demand, as well as difficulties modulating executive control
and salience processing regions with increasing cognitive de-
mand. These findings support the need for future research inves-
tigating the role of default-mode connectivity in contributing
to cognitive symptoms in PTSD and how current or novel in-
terventions may influence PTSD patients’ ability to modulate
these regions.
References
American Psychiatric Association. (1994). Diagnostic and statistical manual
of mental disorders (4th ed.). Washington, DC: Author.
Aupperle, R. L., Allard, C. B., Simmons, A. N., Flagan, T., Thorp, S. R.,
Norman, S. B., . . . Stein, M. B. (2013). Neural responses during emotional
processing before and after cognitive trauma therapy for battered women.
Psychiatry Research, 214, 48–55. doi:10.1016/j.pscychresns.2013.05.001
Aupperle, R. L., Melrose, A. J., Stein, M. B., & Paulus, M. P. (2012). Executive
function and PTSD: Disengaging from trauma. Neuropharmacology, 62,
686–694. doi:10.1016/j.neuropharm.2011.02.008
Barkley, R. A., & Murphy, K. R. (2010). Impairment in occupational func-
tioning and adult ADHD: The predictive utility of executive function (EF)
ratings versus EF tests. Archives of Clinical Neuropsychology, 25, 157–173.
doi:10.1093/arclin/acq014
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman,
F. D., Charney, D. S., & Keane, T. M. (1995). The development of a
Clinician-Administered PTSD Scale. Journal of Traumatic Stress, 8, 75–
90. doi:10.1002/jts.2490080106
Blanchard, E. B., Jones-Alexander, J., Buckley, T. C., & Forneris, C. A. (1996).
Psychometric properties of the PTSD Checklist (PCL). Behavior Research
and Therapy, 34, 669–673. doi:10.1016/0005-7967(96)00033-2
Bressan, R. A., Quarantini, L. C., Andreoli, S. B., Araujo, C., Breen, G., Guin-
dalini, C., . . . Mari, J. J. (2009). The posttraumatic stress disorder project in
Brazil: Neuropsychological, structural and molecular neuroimaging studies
in victims of urban violence. BMC Psychiatry, 9, 30. doi:10.1186/1471-
244X-9-30
Carrion, V. G., Garrett, A., Menon, V., Weems, C. F., & Reiss, A. L.
(2008). Posttraumatic stress symptoms and brain function during a response-
inhibition task: An fMRI study in youth. Depression and Anxiety, 25, 514–
526. doi:10.1002/da.20346
Casada, J. H., & Roache, J. D. (2005). Behavioral inhibition and activation in
posttraumatic stress disorder. Journal of Nervous and Mental Disease, 193,
102–109. doi:10.1097/01.nmd.0000152809.20938.37
Chambers, C. D., Garavan, H., & Bellgrove, M. A. (2009). Insights
into the neural basis of response inhibition from cognitive and clini-
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
39
cal neuroscience. Neuroscience and Biobehavioral Reviews, 33, 631–646.
doi:10.1016/j.neubiorev.2008.08.016
Cox, R. W. (1996). AFNI: Software for analysis and visualization of functional
magnetic resonance neuroimages. Computers and Biomedical Research, 29,
162–173. doi:10.1006/cbmr.1996.0014
Daniels, J. K., McFarlane, A. C., Bluhm, R. L., Moores, K. A., Clark, C.
R., Shaw, M. E., . . . Lanius, R. A. (2010). Switching between executive
and default mode networks in posttraumatic stress disorder: Alterations in
functional connectivity. Journal of Psychiatry and Neuroscience, 35, 258–
266. doi:10.1503/jpn.090010
Delis, D., Kaplan, E., & Kramer, J. (2001). Delis-Kaplan Executive Function
System (D-KEFS): Examiner’s manual. San Antonio, TX: The Psychological
Corporation.
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A
meta-analysis of emotional processing in PTSD, social anxiety disorder,
and specific phobia. The American Journal of Psychiatry, 164, 1476–1488.
doi:10.1176/appi.ajp.2007.07030504
Falconer, E., Allen, A., Felmingham, K. L., Williams, L. M., & Bryant, R. A.
(2013). Inhibitory neural activity predicts response to cognitive-behavioral
therapy for posttraumatic stress disorder. Journal of Clinical Psychiatry, 74,
895–901. doi:10.4088/JCP.12m08020
Falconer, E. M., Felmingham, K. L., Allen, A., Clark, C. R., McFarlane,
A. C., Williams, L. M., & Bryant, R. A. (2008). Developing an inte-
grated brain, behavior and biological response profile in posttraumatic
stress disorder (PTSD). Journal of Integrative Neuroscience, 7, 439–456.
doi:10.1142/S0219635208001873
Fonzo, G. A., Simmons, A. N., Thorp, S. R., Norman, S. B., Paulus, M. P.,
& Stein, M. B. (2010). Exaggerated and disconnected insular-amygdalar
blood oxygenation level-dependent response to threat-related emotional
faces in women with intimate-partner violence posttraumatic stress dis-
order. Biological Psychiatry, 68, 433–441. doi:10.1016/j.biopsych.2010.
04.028
Francati, V., Vermetten, E., & Bremner, J. D. (2007). Functional neuroimaging
studies in posttraumatic stress disorder: Review of current methods and
findings. Depression and Anxiety, 24, 202–218. doi:10.1002/da.20208
Jovanovic, T., Ely, T., Fani, N., Glover, E. M., Gutman, D., Tone, E. B., . . .
Ressler, K. J. (2013). Reduced neural activation during an inhibition task
is associated with impaired fear inhibition in a traumatized civilian sample.
Cortex, 49, 1884–1891. doi:10.1016/j.cortex.2012.08.011
Koso, M., & Hansen, S. (2006). Executive function and memory in posttrau-
matic stress disorder: A study of Bosnian war veterans. European Psychiatry,
21, 167–173. doi:10.1016/j.eurpsy.2005.06.004
Lagarde, G., Doyon, J., & Brunet, A. (2010). Memory and executive dys-
functions associated with acute posttraumatic stress disorder. Psychiatry
Research, 177, 144–149. doi:10.1016/j.psychres.2009.02.002
Leskin, L. P., & White, P. M. (2007). Attentional networks reveal executive
function deficits in posttraumatic stress disorder. Neuropsychology, 21, 275–
284. doi:10.1037/0894-4105.21.3.275
Liberzon, I., & Sripada, C. S. (2008). The functional neuroanatomy of
PTSD: A critical review. Progress in Brain Research, 167, 151–169.
doi:10.1016/S0079-6123(07)67011-3
Litz, B. T., Weathers, F. W., Monaco, V., Herman, D. S., Wulfsohn, M.,
Marx, B., & Keane, T. M. (1996). Attention, arousal, and memory in
posttraumatic stress disorder. Journal of Traumatic Stress, 9, 497–519.
doi:10.1002/jts.2490090308
Matthews, S. C., Simmons, A. N., Arce, E., & Paulus, M. P. (2005). Dissoci-
ation of inhibition from error processing using a parametric inhibitory task
during functional magnetic resonance imaging. Neuroreport, 16, 755–760.
40 Aupperle et al.
Moores, K. A., Clark, C. R., McFarlane, A. C., Brown, G. C., Puce,
A., & Taylor, D. J. (2008). Abnormal recruitment of working mem-
ory updating networks during maintenance of trauma-neutral informa-
tion in post-traumatic stress disorder. Psychiatry Research, 163, 156–170.
doi:10.1016/j.pscychresns.2007.08.011
Ozer, E. J., Best, S. R., Lipsey, T. L., & Weiss, D. S. (2003). Predic-
tors of posttraumatic stress disorder and symptoms in adults: A meta-
analysis. Psychological Bulletin, 129, 52–73. doi:10.1037/1942-9681.S.
1.3
Polak, A. R., Witteveen, A. B., Reitsma, J. B., & Olff, M. (2012). The role
of executive function in posttraumatic stress disorder: A systematic review.
Journal of Affective Disorders, 141, 11–21. doi:10.1016/j.jad.2012.01.001
R Core Team. (2014). R: A language and environment for statistical com-
puting [Computer software]. Vienna, Austria: R Foundation for Statistical
Computing.
Ridderinkhof, K. R., van den Wildenberg, W. P., Segalowitz, S. J., & Carter,
C. S. (2004). Neurocognitive mechanisms of cognitive control: The role
of prefrontal cortex in action selection, response inhibition, performance
monitoring, and reward-based learning. Brain and Cognition, 56, 129–140.
doi:10.1016/j.bandc.2004.09.016
Sadeh, N., Spielberg, J. M., Miller, M. W., Milberg, W. P., Salat, D. H.,
Amick, M. M., . . . McGlinchey, R. E. (2015). Neurobiological indicators
of disinhibition in posttraumatic stress disorder. Human Brain Mapping, 36,
3076–3086. doi:10.1002/hbm.22829
Shin, L. M., Bush, G., Milad, M. R., Lasko, N. B., Brohawn, K. H., Hughes,
K. C., . . . Pitman, R. K. (2011). Exaggerated activation of dorsal anterior
cingulate cortex during cognitive interference: A monozygotic twin study
of posttraumatic stress disorder. American Journal of Psychiatry, 168, 979–
985. doi:10.1176/appi.ajp.2011.09121812
Shin, L. M., & Liberzon, I. (2010). The neurocircuitry of fear,
stress, and anxiety disorders. Neuropsychopharmacology, 35, 169–191.
doi:10.1038/npp.2009.83
Shucard, J. L., McCabe, D. C., & Szymanski, H. (2008). An event-related
potential study of attention deficits in posttraumatic stress disorder during
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
auditory and visual Go/NoGo continuous performance tasks. Biological
Psychology, 79, 223–233. doi:10.1016/j.biopsycho.2008.05.005
Simmonds, D. J., Pekar, J. J., & Mostofsky, S. H. (2008). Meta-analysis
of go/no-go tasks demonstrating that fMRI activation associated with
response inhibition is task-dependent. Neuropsychologia, 46, 224–232.
doi:10.1016/j.neuropsychologia.2007.07.015
Simmons, A. N., & Matthews, S. C. (2011). Neural circuitry of PTSD with or
without mild traumatic brain injury: A meta-analysis. Neuropharmacology,
62, 598–606. doi:10.1016/j.neuropharm.2011.03.016
Sripada, R. K., King, A. P., Welsh, R. C., Garfinkel, S. N., Wang, X.,
Sripada, C. S., & Liberzon, I. (2012). Neural dysregulation in posttrau-
matic stress disorder: Evidence for disrupted equilibrium between salience
and default mode brain networks. Psychosomatic Medicine, 74, 904–911.
doi:10.1097/PSY.0b013e318273bf33
Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human
brain. New York, NY: Thieme Medical Publishers.
Twamley, E. W., Allard, C. B., Thorp, S. R., Norman, S. B., Hami
Cissell, S., Hughes Berardi, K., . . . Stein, M. B. (2009). Cognitive im-
pairment and functioning in PTSD related to intimate partner violence.
Journal of the International Neuropsychological Society, 15, 879–887.
doi:10.1017/S135561770999049X
Verbruggen, F., & Logan, G. D. (2008). Response inhibition in the
stop-signal paradigm. Trends in Cognitive Sciences, 12, 418–424.
doi:10.1016/j.tics.2008.07.005
Weathers, F. W., Huska, J., & Keane, T. M. (1991). The PTSD Checklist Military
Version (PCL-M). Boston, MA: National Center for PTSD.
Yarkoni, T. (2009). Big correlations in little studies: Inflated fMRI corre-
lations reflect low statistical power: Commentary on Vul et al. (2009).
Perspectives on Psychological Science, 4, 294–298. doi:10.1111/j.1745-
6924.2009.01127.x
Zelazo, P. D., & Cunningham, W. A. (2007). Executive function: Mechanisms
underlying emotion regulation. In J. Gross (Ed.), Handbook of emotion
regulation (pp. 135–158). New York, NY: Guilford Press.
Copyright of Journal of Traumatic Stress is the property of John Wiley & Sons, Inc. and its
content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.