Drug and Alcohol Dependence 79 (2005) 273–277
Deficits in response inhibition associated with chronic
John R. Monterossoa,b,∗, Adam R. Aronb, Xochitl Cordovaa,
Jiansong Xua, Edythe D. Londona,c,d
aDepartment of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90024-1759, USA
bDepartment of Psychology, University of California Los Angeles, Los Angeles, CA 90024-1759, USA
cDepartment of Molecular and Medical Pharmacology, Los Angeles, CA 90024-1759, USA
dBrain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024-1759, USA
Received 30 November 2004; received in revised form 2 February 2005; accepted 4 February 2005
Chronic methamphetamine (MA) abuse is associated with cerebral deficits, involving frontal/basal-ganglia regions that are important for
inhibitory control. We used the Stop-Signal Task to measure response inhibition in 11 MA abusers (5–7 days abstinent) and two groups of
to inhibit an initiated motor response, was significantly longer for MA abusers than for either control group (p’s<.01). In contrast, the MA
abusers did not differ from either group on Go trial reaction time (RT) or number of discrimination errors, which reflect motor speed and
decision-processes, respectively. MA abuse in this study was therefore associated with a specific deficit in inhibiting a pre-potent response.
Future research could examine whether SSRT is different for MA abusers who respond to treatment compared to those who do not. If such
differences are established then response inhibition may serve as a marker for investigating MA abuse in basic science and clinical trials.
© 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Methamphetamine; Inhibition; Stop signal task; Neuropsychology
Response inhibition can be defined as the intentional
prevention of a behavior that is underway or that is other-
wise automatically evoked (i.e., “pre-potent”). Experimen-
tally, it can be studied with stop-signal, Go/No-Go and other
inhibitory tasks. It has been hypothesized that response inhi-
pression of rapid conditioned drug-seeking responses may
occur by a similar mechanism as the suppression of a motor
response (Fillmore, 2003; Jentsch and Taylor, 1999; Lyvers,
2000). Response inhibition has been consistently related to
functional activation and structural integrity of the right infe-
rior frontal cortex, and fairly consistently with the basal-
∗Corresponding author. Tel.: +1 310 794 1736; fax: +1 310 825 0812.
E-mail address: firstname.lastname@example.org (J.R. Monterosso).
in press). Response inhibition may be particularly relevant
to methamphetamine (MA) dependence given the range of
frontal/basal-ganglia abnormalities observed in MA abusers,
including low levels of dopamine transporter (McCann et
al., 1998; Sekine et al., 2001, 2003; Volkow et al., 2001b),
low concentrations of N-acetylaspartate (a marker for neu-
ronal integrity) (Ernst et al., 2000), abnormalities in glucose
metabolism (Volkow et al., 2001a; London et al., 2004), and
deficits in gray matter relative to controls (Thompson et al.,
abusers (Chang et al., 2002; Kalechstein et al., 2003; Paulus
et al., 2003; Rogers et al., 1999; Salo et al., 2002; Simon
et al., 2000) indicate impairment on measures associated
with frontal cortical functioning, including verbal and non-
verbal fluency (see Kalechstein et al., 2003) and working
memory (Chang et al., 2002; Simon et al., 2000). Response
0376-8716/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
274 J.R. Monterosso et al. / Drug and Alcohol Dependence 79 (2005) 273–277
inhibition among MA abusers has primarily been assessed in
past studies using paper or computer versions of the Stroop
Color-Word Task (Perret, 1974), which requires inhibition of
reading color names. Both Simon et al. (2000) and Salo et al.
(2002) reported impairment on Stroop performance among
MA users, while Kalechstein et al. (2003) and Chang et al.
(2002) did not find significant deficits among MA abusers on
the task. The discrepancy between these studies may reflect
variability given an underlying modest effect, or may be
related to methodological differences; only Salo et al. (2002)
task, and only Simon et al. included MA abusers who tested
positive for MA on the day of testing.
Compared with the Stroop Task, the Stop-Signal Task is
a more direct means of assessing response inhibition (Logan
et al., 1984, 1997; Nigg, 2000; Quay, 1997). Through a
method described below, the Stop-Signal Task measures the
amount of time (typically on the order of 200ms) required
to inhibit a motor response already initiated. Several lines of
2000 for review), and their performance improves following
administration of methylphenidate (Tannock et al., 1995).
Second, poor performance on the task is correlated with
task relative to controls (Fillmore and Rush, 2002). Consis-
by a variety of factors other than response inhibition (for
review, see MacLeod, 1991) performance on the Stop-Signal
Task does not appear to be well correlated with performance
on the Stroop Task (in Friedman and Miyake (2004) r=.15;
in Avila et al. (2004), r=−.11).
The purpose of this study was to assess whether MA
abusers would demonstrate slower stop-signal response inhi-
bition than control subjects and whether individual differ-
ences among MA abusers in response inhibition would be
correlated with duration and extent of MA abuse.
Since cigarette smoking is common among MA abusers
(e.g., London et al., 2004), we recruited and took informed
consent (in accordance with the Human Subjects Protec-
tion Committee of UCLA) from both a group of control
smokers (n=14), and control non-smokers (n=29) for com-
parison with a group of MA abusers (n=11). Inclusion in
the MA group required testing positive for recent MA use
(and not other illicit drugs), reporting 1 or more years of
using ≥1g of MA per week, and meeting DSM-IV criteria
for MA dependence (Structured Clinical Interview for DSM-
15 cigarettes per day, and have >15ppm of CO in expired air.
Other current axis I diagnoses were exclusionary for partic-
ipants across groups, except for nicotine dependence in the
control smokers and MA abusers. Participants across groups
were excluded if they reported current use of psychotropic
medications, use of any medications known to affect cogni-
tive functioning, were in counseling, taking medication for
psychological problems, or had a history of hospitalization
for psychiatric illness. Participants across groups were also
excluded if they reported a history of head trauma involv-
ing loss of consciousness and/or requiring hospitalization.
Smoker control and MA participants were excluded from
participation if they scored≥46 on the Wender Utah Rating
Scale (not administered to non-smoker controls). Urine sam-
ples were collected from all participants at enrollment. Urine
was tested using a five-panel rapid test from Alfa Scientific
(COC/mAMP/OPI/THC/BZO). A positive drug test resulted
in exclusion from participation for smoker and non-smoker
in the lifetime, but none met diagnostic criteria for current
alcohol (10 subjects, 91%), marijuana (9 subjects, 82%), and
cocaine (eight subjects, 73%). One of the MA abusers (9%)
met criteria for past alcohol abuse, and one other MA abuser
(9%) met criteria for past alcohol dependence. One MA
abuser was included despite testing positive for recent mari-
The groups differed significantly in gender (non-smoker
controls=66.7% women, smoker controls 28.6% women,
and MA 36.4% women; χ2=6.39, d.f.=2, p<.05) and race
(non-smoker controls, 37.0% white, smoker controls, 57.1%
white, and MA abusers, 81.8% white; χ2=6.48, d.f.=2,
p<.05), but not in age (overall 27.5±9.1), IQ estimate
(106.1±9.6), years of education (13.9±2), or, for the MA
abusers and smoker controls, WURS score (22.6±11). MA
per week. Six of the 11 MA participants (54.5%) reported
smoking as their primary route of MA administration (two
injecting, two snorting, one oral). MA abusers used an aver-
years. Eight of the MA abusers (72.7%) were also cigarette
This study of Stop-Signal performance was conducted as
an addendum to an ongoing functional and structural neu-
is included in that ongoing study, data from that battery are
collected in a different test session and were not available at
the time of this report.
MA participants were housed for 5–7 days of abstinence
(verified based on urine test) at the UCLA General Clini-
cal Research Center prior to participation; both other groups
participated on a non-residential basis. Urine samples were
J.R. Monterosso et al. / Drug and Alcohol Dependence 79 (2005) 273–277275
collected every day from MA abusers and tested randomly,
at least twice a week, to ensure abstinence during participa-
was excluded after remaining positive for MA after 1 week
of inpatient stay, suggesting continued use.
The Stop-Signal Task was performed according to the
method outlined by Logan et al. (1997). Briefly, each of 256
trials started with the presentation of a fixation dot (500ms)
followed by a target stimulus, “O” or “X”, which remained
completing a response if a target was followed by a “stop-
delay (Stop-Signal Delay, “SSD”) after the target stimulus
by 50ms, and after a failed stop-trial, it was decreased by
50ms, thereby converging on a SSD resulting in approxi-
mately 50% successful inhibition rate. Stop-signal reaction
time (SSRT) was computed as the difference between mean
RT on Go trials, and the averaged SSD.
According to the race-model of performance on the task
(Logan et al., 1984), the initial target sets a “go-response”
in motion and the stop-signal sets an independent “stop-
response” in motion. Stopping is successful if the stop-
response is completed before the go-response is completed.
As such, the difference between the mean RT on go-trials
provides an index of the time it takes participants to execute
the stop-process. Since initial SSD values (which started at
200ms) might have been far from SSD values after titra-
tion, the first 64 trials (16 stop trials) were discarded. SSRT,
Fig. 1. Stop-Signal Task performance. Data indicate 95% confidence inter-
val on three Stop-Signal Task measures: SSRT (an index of response inhibi-
tion), RT (on Go trials), and error rates (on Go trials). SSRT and RT are in
ms (left ordinate), while error rate is in percentage. Dotted lines and dotted
bar represent non-smoker controls, dashed lines and dashed bars represent
smoker controls, and full lines and bar with full lines represent MA abusers.
were not significantly different on other measures.
Fig. 2. Scatterplot of stop-signal reaction time (SSRT, ms) vs. MA use [ln
(g/week)]. MA use was significantly correlated (p<.05) with SSRT.
RT on Go trials, and % errors on Go trials were compared
across study groups. Secondary analyses assessed the asso-
ciation between SSRT and both years and rate (g/week) of
Success on stop-signal trials was 48.3% and did not differ
cessful. One-way analyses of variance indicated no signifi-
p=.62), or in error rates (F(2, 51)=2.2, p=.13) on Go tri-
als. A main effect was observed on SSRT (F(2, 51)=13.7,
p<.001). Post hoc analyses (using the Bonferroni correc-
tion) indicated that MA participants had slower SSRTs than
both control groups (p’s<.01), while the two control groups
did not differ from one another (Fig. 1). Regression analysis
indicated that SSRTs of the MA users were not significantly
correlated with years of use (r(11)=−.26, p=.44), but were
correlated with current amount of MA used (g/week normal-
ized by natural log transformation to remove a significant
positive skew; r(11)=.62, p=.04; Fig. 2).
This study shows slower response inhibition among
recently abstinent MA abusers on the Stop-Signal Task rela-
tive to healthy control subjects. A small group (n=11) of
recently abstinent MA abusers exhibited markedly worse
performance than either comparison group on response inhi-
276 J.R. Monterosso et al. / Drug and Alcohol Dependence 79 (2005) 273–277
bition, but not on reaction times or errors on non-inhibition
trials. The results also suggest that individual differences
among MA abusers in response inhibition are related to
the recent amount of MA use. Given that the right infe-
rior frontal gyrus and (less consistently) the basal-ganglia
have been implicated in response inhibition (Aron and
in both these regions are reasonable candidates to underlie
this deficit. Worth considering in this regard are structural
recent suggestive evidence (not significant after correction
among MA abusers (Thompson et al., 2004).
Several caveats warrant mention. MA participants had
more extensive drug use histories beyond MA than did the
control participants. They also had significantly more male
participants than one of the two control groups, and were
more predominantly Caucasian than control groups, as well
as differing no doubt in myriad unmeasured ways. Also,
MA abusers but not control groups completed the Stop-
Signal Task as inpatients, which could conceivably have
affected performance. Furthermore, MA withdrawal pro-
duces fairly severe anhedonia, irritability, and poor concen-
tration (Newton et al., 2004). While preliminary data suggest
that these symptoms dramatically improve over the first few
days of abstinence (Newton et al., 2004), and we did not
administer the Stop-Signal Task until MA participants were
beyond the severe “crash” and felt ready for testing, it is
possible that transient withdrawal symptoms contributed to
performance deficits. It is worth noting, however, that the
MA group did not differ from control groups in performance
on task measures not related to response inhibition (RT and
accuracy on go-trials), suggesting some degree of specificity
to the deficiency.
Despite important caveats, the magnitude of the observed
difference suggests a robust association between response
inhibition and MA abuse. These data do not allow any infer-
ence regarding the extent to which poor response inhibition
preceded MA abuse (and perhaps contributed causally to its
development), as opposed to followed MA abuse (perhaps
developing as a consequence of MAs neurotoxicity). Cog-
nitive impairment in general, however, has been associated
with poorer treatment outcomes (Aharonovich et al., 2003;
Fals-Stewart, 1993). Future research could examine whether
SSRT is different for MA abusers who respond to treatment
compared to those who do not. If such differences are estab-
lished then response inhibition may serve as a marker for
investigating MA abuse in basic science and clinical trials.
Supported by NIH Grant K01 DA0051-01A1 (JM),
NIH Grant 3R01 DA015179-02S1 (EDL), and UCLA
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