Topic: Denial in methamphetamine users: Associations with cognition and functional connectivity in brain

Despite the negative impact on one’s health and quality of life,
individuals who have drug use disorders may deny having a problem with drugs. Indeed, traditional models of addiction treatment,
such as that embraced by Alcoholics Anonymous, conceptualize
denial as a hallmark of the addictive process (Kurtz, 1982). More
contemporary models of behavior change in addiction, such as the
Transtheoretical Model (DiClemente et al., 2004; Prochaska et al.,
∗ Corresponding author at: UCLA Semel Institute for Neuroscience and Human
Behavior, 760 Westwood Plaza, Los Angeles, CA 90095-1759, USA.
Tel.: +1 310 825 5839; fax: +1 310 825 0812.
E-mail address: acdean@mednet.ucla.edu (A.C. Dean).
1992), likewise suggest that individuals who abuse substances
may deny or fail to recognize the need to change their behavior, and that only through insight into the problem and intrinsic
motivation can true behavioral change take place. This view is
consistent with evidence suggesting that, among those who meet
criteria for methamphetamine dependence, lack of perceived need
for treatment is one of the most problematic barriers to treatment
utilization (Kenny et al., 2011).
An emerging literature suggests that abnormalities in cognition
and brain function may reduce the degree to which drug users can
reflect upon and have insight into the nature of their substance
abuse (see Goldstein et al., 2009). The relevant evidence has raised
the possibility that denial by substance users may reflect a deficit
in self-awareness and/or interoceptive monitoring, rather than, or
in addition to, a conscious or subconscious attempt by the drug
http://dx.doi.org/10.1016/j.drugalcdep.2015.03.004
0376-8716/© 2015 Elsevier Ireland Ltd. All rights reserved.
A.C. Dean et al. / Drug and Alcohol Dependence 151 (2015) 84–91 85
user to minimize his or her symptoms (Goldstein et al., 2009).
Limited research, however, has examined potential neurocognitive
contributions to denial in addiction. A preliminary study of individuals in treatment for alcohol dependence found that participants
who were judged by clinicians to have more denial regarding their
addiction exhibited worse performance on tests of executive functioning, memory, and processing speed than their counterparts
who were thought to have less denial (Rinn et al., 2002). However, other studies of cognitive or neural contributions to denial
in substance users have not been conducted.
Research has indicated that individuals who abuse drugs may
have less awareness of their behavior than those who do not
abuse drugs. When compared to healthy control subjects, cocaine
users have shown less awareness of their choices when viewing
emotional and cocaine-related images (Moeller et al., 2010), and
of errors they made when performing an inhibitory control task
(Hester et al., 2007). In alcohol-abusing college students, reduced
awareness of drinking problems was associated with worse performance on memory tests (Blume et al., 2000). Marijuana users
completing a go/no-go task while undergoing functional magnetic
resonance imaging (fMRI) had less awareness of errors and less
error-associated BOLD activation in the anterior cingulate cortex (ACC) and right insula than healthy control subjects (Hester
et al., 2009). Similarly, cocaine users with limited insight into their
choices for emotional and drug-related images exhibited less activation of the rostral ACC (rACC) during errors on an fMRI Stroop
Task, and had less gray matter volume in the rACC,than participants
with intact insight (Moeller et al., 2014).
Evidence from error-monitoring studies in healthy subjects has
likewise suggested that the rACC and insula contribute to one’s
awareness of having made errors during task performance (Klein
et al., 2007; Simoes-Franklin et al., 2010; Taylor et al., 2007). The
anterior portion of the insula, in particular, is considered to be
important in the integration of interoceptive states with environmental conditions necessary for self-awareness (Craig, 2009). In
the resting state, the anterior insula and ACC act as a “salience network” that is sensitive to detecting inconsistencies in oneself or the
environment, and serves to activate other brain regions for further
processing of personally relevant information (Menon and Uddin,
2010).
There is also evidence that, in addition to the rACC and anterior
insula, the precuneus is involved in self-awareness (see Cavanna
and Trimble, 2006). In healthy participants, the level of activation of the precuneus is positively associated with the degree to
which subjects are aware of internal thoughts and feelings compared to stimuli in the external environment (Vanhaudenhuyse
et al., 2010). Further, transcranial magnetic stimulation of the precuneus inhibits the retrieval of judgments about oneself but not
about others (Lou et al., 2004). Schizophrenic patients with low
insight into their psychosis exhibit hypoperfusion of the precuneus
compared with patients who have intact insight (Faget-Agius et al.,
2012). Schizophrenic patients with poor insightinto their condition
also show less resting-state functional connectivity (RSFC) between
the default mode network and the precuneus and ACC than those
with greater insight (Liemburg et al., 2012). Notably, research
participants who meet DSM-IV criteria for methamphetamine
dependence also exhibit gray-matter deficits and task-related
abnormalities in the precuneus,ACC and insula (London et al., 2005;
Morales et al., 2012; Nestor et al., 2011; Thompson et al., 2004);
however, the relationship between these abnormalities and denial
or insight regarding their addiction has not been evaluated.
Given evidence of neurocognitive contributions to selfawareness in substance users, we evaluated whether denial of
substance use problems is related to cognitive performance and
RSFC of regions previously associated with self-awareness (i.e.,
rACC, anterior insula and precuneus)in a sample of individuals who
met criteria for current methamphetamine dependence according
to DSM-IV criteria (58 participants with cognitive tests, 21 of whom
also had fMRI scans). Denial was assessed with the University of
Rhode Island Change Assessment (URICA) precontemplation subscale. This subscale is a measure ofthe degree to which participants
deny having problems they wish to change, and has been conceptualized as assessing denial of problems (e.g., Dare and Derigne, 2010;
Peteet et al., 1998; Zimmerman et al., 2000). Consistent with the
aforementioned literature, the hypotheses tested were that denial
of problems would be negatively associated with overall cognitive
performance and with the strength of connectivity of the rACC,
anterior insula and precuneus with regions important for decisionmaking and affect (e.g., prefrontal cortex, limbic regions).

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Study level: Master
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Subject: Art and Design
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