'gamified' working memory training for addicted adolescents

During adolescence, young people show a steady increase in new but sometimes
risky behaviors, such as smoking, alcohol consumption and drug use (Steinberg,
2005). According to recent statistics, the lifetime prevalence of Dutch
adolescents' alcohol and substance use increases from the age of 12. To
illustrate, substance use estimates based on a representative sample of Dutch
students in 2011 indicated that life-time prevalence rates for alcohol use
varied between 35.4% in 12 year-olds and 93.4% in 17-18 year-olds and for
cannabis use between 1.2 % in 12 year-olds and 44.6% in 17-18 year-olds
(Verdurmen et al., 2012).

Use of alcohol and drugs can lead to a range of negative consequences on the
short term e.g. acute health damage, accidents, vandalism, and sexual risk
taking (Chen & Lin, 2009; Degenhardt & Hall, 2012; Rehm, 2011; Rehm, Taylor, &
Room, 2006) but it can also affect long-term outcomes by increasing the risk of
developing serious health problems and/or substance use dependence later in
life (Chen, Storr, & Anthony, 2009; Ellickson, Tucker, & Klein, 2003; Norstrom
& Ramstedt, 2005). As their brain and physique are not fully grown yet,
adolescents show increased susceptibility to the effects of alcohol and drugs
and to the associated risk of developing substance use problems and/ or
dependence (Chambers, Taylor, & Potenza, 2003; Dayan, Bernard, Olliac, Mailhes,
& Kermarrec, 2010; Schramm-Sapyta, Walker, Caster, Levin, & Kuhn, 2009).
Problematic substance use and substance use dependence can already occur during
the adolescent years and the mean age for developing a SUD is estimated at 15
(Merikangas et al., 2010). Prevalence estimates of the NEMESIS-study suggest
that about 24.6 per cent of the 18 to 24-year-olds in the Dutch general
population have ever experienced a SUD (De Graaf, Ten Have, & Van Dorsselaer,
2010). Unfortunately, recent data on substance use disorders among Dutch
adolescents below 18 years of age are lacking.

Since the influential article by Leshner, addiction is recognized as *a
chronic, relapsing brain disorder characterized by compulsive drug seeking*
which should preferably be treated as early as possible (Leshner, 1997). This
risk of developing a chronic disease stresses the importance of effective
treatments for adolescents who already experience substance use problems. The
need for addiction treatment is also warranted because of acute negative
consequences that addicted adolescents and their families experience. Substance
use disorders can result in significant problems across a range of domains
including (psychological) health, school, family, friendships/social relations,
and the law (Dennis, Dawud-Noursi, Muck, & McDermeit, 2002; Tims et al., 2002).
Only part of the adolescent population with SUD enters treatment. In 2011, a
total of 8,130 Dutch young patients received treatment for their addiction
problems (Wisselink, Kuijpers, & Mol, 2012). Moreover, the number of patients
in the ages between 10 and 25 years in Dutch addiction care facilities has
increased slightly over the past 10 years.

Currently, evidence-based therapies for adolescents with SUD include mainly
psychosocial interventions since there are few controlled studies assessing the
effectiveness of pharmacotherapy in adolescent populations (Clark, 2012;
Waxmonsky & Wilens, 2005). The most commonly applied and most frequently tested
form of treatment is Cognitive Behavioral Therapy (CBT), often combined with
Motivational Interviewing (Kaminer, 2002; Waldron & Kaminer, 2004; Winters,
Botzet, & Fahnhorst, 2011). Also, family therapy (such as Multidimensional
Family Therapy) has been shown effective in treating adolescents with SUD
(Hendriks, van der Schee, & Blanken, 2011; Liddle et al., 2001). Unfortunately,
despite significant reductions in substance use, post-treatment relapse rates
remain high (Cornelius et al., 2003; Simpson, Joe, Rowan-Szal, & Greener, 1997;
Winters, et al., 2011). For example, in the study by Hendriks et. al. (2011)
only 17% of the patients remained abstinent after 1 year, and half of them
still fulfilled the diagnostic criteria for SUD. These treatment outcomes
emphasize the need for further improvement of current treatment practices. The
proposed project aims to contribute to the advancement of adolescent addiction
care programs by testing a new, promising intervention that can be included as
an add-on to the usual treatment regimen.

Working memory, the main target of the intervention that will be tested, has
become an influential concept in cognitive psychology and is described as a
cognitive system that controls the active maintenance and storage of short-term
information during additional cognitive processing and/or distraction (Conway
et al., 2005). The system is recognized as a key factor in complex cognitive
behaviors, such as comprehension, reasoning, and problem solving (Engle, 2002;
Kyllonen & Christal, 1990; Myake & Shah, 1999). Deficits in working memory have
been associated with learning (Gathercole & Alloway, 2006) as well as
psychiatric disorders such as schizophrenia (Twamley, Jeste, & Bellack, 2003),
ADHD (Martinussen, Hayden, Hogg-Johnson, & Tannock, 2005) and SUD (Jovanovski,
Erb, & Zakzanis, 2005; Sofuoglu, Sugarman, & Carroll, 2010).

Since the influential publication by Klingberg and colleagues (2002), evidence
is accumulating that working memory can be trained, potentially leading to
beneficial outcomes across different domains. In children and adults with ADHD,
training of working memory resulted in improved executive functioning and
higher-order abilities such as reasoning (Klingberg, Forssberg, & Westerberg,
2002). In another sample of children with ADHD, working memory training
significantly reduced the severity of ADHD symptoms (Klingberg et al., 2005).
Similar beneficial outcomes were found in non-clinical samples indicating that
working memory training improved reasoning and problem solving skills (Jaeggi,
Buschkuehl, Jonides, & Perriq, 2008). Moreover, even in patients with
schizophrenia (Subramaniam et al., 2012) a working memory training resulted in
diminished complaints.

For the treatment of substance use disorders, Aharonovich and colleagues
already identified cognitive abilities, such as working memory capacity, as
potential treatment targets based on their findings that addicted patients with
relatively high levels of cognitive impairments were more likely to drop out
from cognitive-behavioral treatment and showed higher relapse rates than
patients with low levels of cognitive impairment (Aharonovich, Brooks, Nunes, &
Hasin, 2008; Aharonovich et al., 2006; Aharonovich, Nunes, & Hasin, 2003).
Following this line of reasoning, some researchers addressed the efficacy of
computer-assisted cognitive rehabilitation programs (which include a wide range
of different cognitive exercises to train different aspects of cognitive
functioning) and found that this type of interventions can improve cognitive
functions in adult patients with SUD (Fals-Stewart & Lam, 2010; Fals-Stewart &
Lucente, 1994; Rupp, Kemmler, Kurz, Hinterhuber, & Fleischhacker, 2012). In
addition, two recent studies provided support for the potential benefits of
cognitive training programs that specifically target working memory capacity in
problem drinkers (Houben, Wiers, & Jansen, 2011) and patients with stimulant
addiction (Bickel, Yi, Landes, Hill, & Baxter, 2011). According to the findings
by Houben et al. (2011) problem drinkers who had trained their working memory
showed improved working memory and reduced alcohol intake one month after the
training. Moreover, the working memory training was particularly effective in
reducing alcohol consumption in participants with relatively strong automatic
preferences for alcohol. In stimulant abusing patients, a working memory
training reduced participants* level of delay discounting (Bickel, et al.,
2011). Delay discounting refers to the preference of sooner, smaller rewards
over later, larger rewards and is associated with risky and disadvantageous
behaviors such as drug dependence, problem gambling, and obesity (Bickel,
Jarmolowicz, Mueller, Koffarnus, & Gatchalian, 2012).

Based on these previous findings, we expect that a computer-assisted working
memory training might also generate positive outcomes in adolescents receiving
treatment for SUD.
However, current computer-assisted programs for working memory training involve
a lot of repetitious and, for adolescents, often tedious exercises which might
lead to low completion rates. A new direction for the development of
computer-assisted and e-health interventions is the use of gaming formats and
principles to encourage consumer*s motivation to adhere to the intervention
(Baranowski, Buday, Thompson, & Baranowski, 2008; Deterding, Dixon, Khaled, &
Nacke, 2001). Game-elements such as virtual worlds, rewards, challenges,
competition, and social interaction generate experiences such as immersion,
pleasure, or surprise which directly fulfill basic motivational behavioural
needs (Przybylski, Rigby, & Ryan, 2010) and enhance players* motivation to
commence or continue playing the game. Prins and colleagues (2011) demonstrated
that application of game elements in a working memory training generated
favorable outcomes in children with ADHD (Prins, Dovis, Ponsioen, ten Brink, &
van der Oord, 2011). Following their example, we developed a working memory
training in game-format for addicted adolescents.

The proposed research project will examine the potential benefits of a
*gamified* working memory training for adolescents in addiction care. The
primary objective is to test whether a gamified working memory training will
lead to improved working memory capacity in addicted adolescents. As a
secondary aim of this project we wil explore the potentially advantageous
effects of the gamified working memory training on addicted adolescents*
capacities on other aspects of working memory, craving, mood states, relapse
rates, delay discounting, and substance use patterns. Finally, in an additional
research question, we will examine whether adolescent patients with an
addiction will show less working memory capacity compared to healthy,
non-addicted adolescents.

In a randomized controlled trial (RCT) with a pre-post design, 68 patients with
a Substance Use Disorder (SUD) who receive inpatient treatment for their
addiction will be randomly assigned to either a working memory training or a
placebo-training (i.e., working memory exercises with low difficulty and not
customized to participants* ability levels). In addition, 64 healthy,
non-addicted peers will be recruited outside the treatment setting and will be
asked to perform only the baseline assessment of the RCT. This non-addicted
non-patient group will function as a reference group to examine differences in
working memory capacity at baseline between addicted adolescents and healthy
controls.

After having provided informed consent, addicted adolescent patients who
participate in the RCT will be asked to perform the training program in the
second month of their stay at the treatment clinic to ensure that they have
enough time to adjust to the usual treatment program first. Before starting the
training, patients will complete a pre-test consisting of a short questionnaire
and several computer-assisted exercises to assess their working memory
capacity. The questionnaire will assess craving (desire) to use substances,
feelings of anxiety and depression. Besides this questionnaire, data on
participants* frequency of substance use before treatment entrance will be
retrieved from the routine outcome assessment that patients fill in before
entering the clinical detox program that precedes the clinical treatment
program.

In the four weeks following the pretest, patients will receive the working
memory intervention three times a week during sessions of 30 minutes (a total
of 12 sessions). The training sessions will take place during fixed time points
and will be integrated in the clinical treatment program. Patients will have
access to the training via a computer at the clinic and will perform the
exercises under supervision of a research assistant. The training will
systematically teach patients how to utilize their working memory on a variety
of domains.

At the end of the last training session (two months after the pre-test),
patients complete the immediate post-test including the same measures as during
the pretest (except frequency of substance use, since patients are still in the
clinic where abstention is required). At the end of the usual clinical
treatment program (about four months after the pre-test) patients will perform
a second post-test including the same measures as the immediate post-test.

Finally, three months after ending the clinical treatment program, patients
will receive a short follow-up assessment in the form of a telephone interview
to determine whether the working memory training had a positive effect on
adolescents* levels of substance use. Assuming that patients in the training
condition have benefited from the working memory intervention, we expect that
they will show a stronger decrease in substance use compared to patients in
the control condition.

The intervention consists of eight working memory exercises that are integrated
in a computer game. This computer game can be characterized as a role-playing
game (rpg) where players can develop and upgrade their playing character during
the game. To upgrade their character, players have to battle against different
enemies. The battles consist of working memory exercises. The difficulty level
of these exercises are customized to the abilities of the player.

The training will systematically teach individuals to utilize their working
memory on different domains. The working memory training consists of eight
different memory tasks, i.e. two versions of the simon task, two versions of
the digit span, the N-back task, the symmetry span task, the operation span
task and the figure task (see for a detailed description paragraph 3.1 of the
research protocol).

The gamified working memory training and the placebo training are identical
except that in the working memory training, the difficulty level of the
exercises increases with the abilities of the player. In contrast, the
difficulty level of the placebo-training does not increase and remains low.
This way, adolescents who receive the intervention will train their working
memory capacity while adolescents who receive the placebo training will not.
The total duration of the intervention amounts to four weeks of three weekly
sessions of 30 minutes resulting in 12 sessions.

No risks are associated with participation. The benefit is an earlier and
possibly effective treatment outcome.