Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers



Status:Recruiting
Conditions:Smoking Cessation, Tobacco Consumers
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:18 - 60
Updated:4/17/2018
Start Date:March 2018
End Date:November 2019
Contact:William V Lechner, Ph.D.
Email:wlechner@kent.edu
Phone:814-450-1093

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Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers: 2x2 Factorial Study

Smoking remains the leading cause of preventable death in the United States, and current
first-line treatments leave the majority of tobacco dependent individuals unable to quit. The
inability to quit despite motivation to do so, is thought to result in part, from
self-control failure. Working memory (WM) deficits contribute to imbalanced self-control and
allow automatic impulses to drive behavior. Thus, WM plays a critical role in addictive
behavior, and is particularly relevant to smoking. Indeed, a strong link between WM and
smoking has been established in the literature; most notably, degree of WM impairment and
deficits in activation in associated brain regions predict time to relapse, and WM moderates
the relationship between craving and relapse. Given these insights, researchers have been
examining interventions that may target WM including WM training (WMT) and repetitive
Transcranial Magnetic Stimulation (rTMS). WMT involves taxing this executive function
repeatedly over time and has shown positive preliminary results in improving measures of
self-control and reducing consumption of addictive substances. Similarly, rTMS, a
non-invasive brain stimulation procedure that stimulates neuronal tissues and increases
cortical excitability, has been shown to increase WM capacity and reduce craving and
consumption of several addictive substances including nicotine. While these interventions
have demonstrated initial promise in affecting addictive behaviors, the magnitude and
durability of their effects may be limited. Recently, researchers have posited — but not yet
empirically tested — that WMT administered in combination with rTMS may result in an additive
or supra-additive effect in treating addictive processes. This is highly significant; the
clinical utility of rTMS over current first line treatments may be limited if factors with
potential to enhance its effectiveness are not examined. Given these recent advances in the
literature, the primary objective of the proposed study is to evaluate the individual and
combined effects of Working Memory (WM) training and repetitive Transcranial Magnetic
Stimulation (rTMS) on WM performance and smoking behaviors as well as critical mediators of
these effects. These aims will be examined in a sample of tobacco dependent adults (N=130)
utilizing a 2x2 factorial experimental design including four groups (WMT+rTMS, sham WMT+rTMS,
WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating independent and combined effects
of WMT and rTMS.

SPECIFIC AIMS Smoking remains the leading cause of preventable death in the U.S. Current
first line treatments leave approximately 70% of tobacco dependent individuals unsuccessful
in their attempt to quit. Specifically, only 5-30% of those who initiate treatment, including
intensive first-line interventions, are able to maintain abstinence for one or more years.
The inability to quit despite motivation to do so is thought to result, in part, from
self-control failure and can be understood within the framework of dual process models of
addiction. Dual process models view vulnerability to tobacco dependence as the relative
balance between automatic impulses and control processes orchestrated through the interplay
of multiple executive function. Working memory (WM) is an executive function associated with
updating information to solve immediate problems, and achieve current goals. WM is a key
cognitive process underlying the regulatory control component of dual process models and is
involved in the initiation, maintenance, and relapse stages of tobacco dependence. Most
notably, deficits in WM performance and activation in associated brain regions predict time
to relapse and strong WM has been shown to reduce the effect of craving on the ability to
resist smoking. Given this relationship, individuals with tobacco dependence are likely to
benefit from interventions that strengthen WM. Recently, several studies have demonstrated
that increasing WM capacity through WM training (WMT) is associated with positive outcomes in
several populations with substance use or impulse control disorders. Specifically, studies
have demonstrated that WMT is associated with decreased: delay discounting in substance
users, weight re-gain after a weight loss program, and alcohol use in heavy drinkers.

A second emerging innovation in the treatment of addictions is repetitive Transcranial
Magnetic Stimulation (rTMS), a procedure which sends magnetic pulses through the scalp to
stimulate neuronal tissue resulting in observed changes in neuronal plasticity and striatal
dopamine. rTMS has now demonstrated positive effects in several substance use disorders
including nicotine, alcohol, and stimulant dependence. This procedure has been shown to be
effective in reducing smoking urges in abstinent as well as satiated smokers and to reduce
cigarette consumption. While promising results for this treatment have been demonstrated, the
size and durability of the therapeutic effect may be limited. Additionally, the mechanism by
which rTMS exerts positive effects on smoking outcomes is unknown. Recently it has been
posited that changes in WM performance resulting from rTMS may be the key pathway to its
observed effects on smoking related outcomes, and furthermore that WMT administered in close
temporal precedence to rTMS may result in an additive or supra-additive effect in treating
addictive processes. However, these hypotheses have not been tested to date despite their
importance for understanding and improving the clinical impact of these emerging therapeutic
modalities for treating addictive behaviors. Interventions with the ability to effectively
target self-control processes fill in a critical gap in currently available treatment
options.

The primary objective of the proposed study is to evaluate the potential for improved effects
and examine mediating pathways of WMT in combination with rTMS on a laboratory based smoking
task and neuropsychological measures of WM performance. These aims will be examined in a
sample of tobacco dependent adults (N=130) utilizing a 2x2 factorial design including four
groups (WMT+rTMS, sham WMT+rTMS, WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating
independent and combined effects of WMT and rTMS. The study will include a baseline
laboratory assessment, 10 WMT sessions over two weeks, followed by 10 days of WMT immediately
preceding and following brain stimulation sessions (10 Hz rTMS, 2000 pulses per session,
applied to left DLPFC). Neurocognitive and psychological mediators will be assessed between
baseline and final laboratory assessment. Lastly, a follow-up assessment will occur one-month
after the final laboratory visit. The proposed study will test the following Specific Aims:

Aim 1: To test the potential for improved effects of combining WMT with rTMS on smoking
behaviors as compared to the independent effects of either condition alone. Hypothesis:
Single active conditions (WMT+sham rTMS and sham WMT+rTMS) will result in significant
increases in time to lapse on an analogue task as compared to the double sham condition (sham
WMT+sham rTMS), and the WMT+rTMS condition will result in significant increases in time to
lapse as compared to the single active conditions.

Aim 2: To test the potential for improved effects of combining WMT with rTMS on WM
performance.

Hypothesis: WMT + rTMS will result in significant increases in WM performance as compared to
all other conditions, including the additive increases in conditions outlined in Aim 1.

Aim 3: To test mediating pathways of the effects rTMS on smoking behaviors including changes
in craving, mood, and WM performance. Hypothesis: The direct effect of rTMS on smoking
outcomes will be mediated by gains in WM performance, and this effect will be largest in the
WMT+rTMS condition.

Inclusion Criteria:

- meet safety guidelines for application of rTMS

- be 18-60 years of age

- have smoked cigarettes regularly for at least one year

- currently smoke at least 10 cigarettes per day

- have a carbon monoxide (CO) level >10 ppm

- currently use no other nicotine products regularly

Exclusion Criteria:

- meet criteria for current alcohol or substance dependence

- have a current affective disorder (depression, dysthymia, or mania) or psychotic
symptoms

- are currently pregnant or lactating, or intend to become pregnant

- have a health condition for which rTMS is contraindicated
We found this trial at
2
sites
69 Brown Street
Providence, Rhode Island 02912
(401) 863-1000
Brown University Located in historic Providence, Rhode Island and founded in 1764, Brown University is...
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345 Blackstone Blvd
Providence, Rhode Island 02906
(401) 455-6200
Butler Hospital Founded in 1844, Butler Hospital is the state's only non-profit, free-standing psychiatric hospital...
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Providence, RI
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