The longitudinal effects of repetitive tDCS on cigarette consumption: An ecological momentary assessment (EMA) study

Tobacco use leads to the largest number of preventable deaths world-wide and
costs billions of dollars each year. Currently available treatments such as
nicotine supplements seem to have limited efficacy, since tobacco users who try
to quit smoking often fail in doing so. Improvement of treatment interventions
in nicotine addiction may be accomplished by focusing on the modulation of
neuronal activity, since substance use disorders (SUDs) are associated with
neurocognitive aberrations.

The dorsolateral prefrontal cortex (dlPFC) has been a target area of interest
in non-invasive neuromodulation studies among tobacco users and other
substances of abuse. Transcranial direct current stimulation (tDCS), a
non-invasive neuromodulation technique, diminished cue-induced craving in
smokers when the anode was placed over the right dlPFC. Furthermore, it was
found that a single tDCS session could increase the time till smoking the first
cigarette after the intervention. More interesting however, is whether actual
cigarette consumption decreases due to tDCS. Only one study has focused on this
area of interest. They found that after five consecutive days of tDCS cigarette
smoking had decreased according to subject*s self-reported measures, but not
when using a carbon monoxide monitor.

These mixed findings may be caused by bias in subjects* responses to
retrospective self-reports. To overcome this problem, the current study aims to
further explore the effects of repetitive tDCS on cigarette consumption by
means of ecological momentary assessments (EMAs). EMA makes it possible to
repeatedly measure craving and cigarette use at random moments of the day, and
seems to result in more reliable and representative measures of craving and
drug use compared to retrospective self-reports. Consequently, EMA offers an
ecologically valid research tool in exploring the therapeutic effects of tDCS.

To optimize the therapeutic effects of tDCS, the interventions will consist of
twice daily sessions of bilateral tDCS over the dlPFC (left cathodal / right
anodal) for three days. Previous studies suggest that repetitive tDCS over the
dlPFC (left cathodal/right anodal) is the most effective treatment intervention
in addiction. Furthermore, twice daily sessions seem to produce long-term
effects and would therefore be particularly interesting to study in nicotine
addiction.

The second aim of the study is to explore the working mechanism behind the
therapeutic effects of repetitive tDCS in nicotine addiction. It is suggested
that tDCS over the dlPFC modulates the activity in this brain area. Decreased
brain activity in the dlPFC is related to nicotine addiction, and this decrease
is believed to be associated with diminished cognitive control. For example,
smokers show aberrations in inhibitory control and risk-taking compared to
non-smokers. Risk-taking seems to be reward-sensitive, and so it is suggested
that when experiencing the urge to use drugs, an unbalance between inhibitory
control and reward processing may lead to the actual decision to use tobacco.
To examine this hypothesis, behavioural and electrophysiological measures of
inhibitory control and risk-taking will be assessed. It is expected that tDCS
will enhance cognitive control functioning, leading to less craving and
cigarette consumption.

(References see page 8 and 9 in research protocol)

The primary objective of the study is to explore the effect of repetitive tDCS
(left cathodal/right anodal) on mean daily cigarette consumption three months
after tDCS by means of ecological momentary assessments (EMAs).

To examine the course of cigarette consumption after repetitive tDCS, starting
on the first treatment day until one week after the last tDCS intervention
(total of 14 days).

The secondary objective is to explore the working mechanism behind the
therapeutic effects of repetitive tDCS in nicotine addiction by means of
craving, and behavioural and electrophysiological responses of risk-taking and
inhibitory control.

The design of the proposed experiment is a double-blind randomized
placebo-controlled trial. Eighty smokers will be randomly assigned to two
conditions, namely tDCS or sham (placebo). Both the researcher as well as the
patient will be blinded of the condition they are in.

Participants will receive tDCS for three days in one week. During these days,
participants receive tDCS or sham twice daily for 13 minutes with an interval
of 20 min. Also, on the first treatment day and the day after the treatment
week, participants complete a number of questionnaires, and perform two
psychological tasks (BART task and the Go/NoGo task). During these tasks
event-related potentials will be recorded by means of EEG. After three months,
participants are asked to return to fill out the same questionnaires and
perform the same psychological tasks as before, to measure the lasting effect
of tDCS. During this last session, event-related potentials will also be
recorded. Also, carbon monoxide levels will be measured on all days where
subjects perform the tasks.

Furthermore, for three weeks, starting the week before tDCS treatment,
participants are asked to log every cigarette before they smoke one. During
these weeks, participants also complete EMA questionnaires about cigarette
consumption, craving, and affect that will take approximately 10 minutes. The
EMA questionnaire will be presented four times daily on a quasi-random basis.
Finally, during end-of-day and morning assessments participants have the
possibility to indicate any missed cigarettes. At three months follow-up,
participants are asked to undergo the same EMA procedure for one more week, to
study the lasting effects of tDCS.

One group receives bilateral tDCS (left cathodal/right anodal) over the DLPFC.
The stimulation will take place two times daily for 13 minutes with a rest
interval of 20 minutes for five consecutive days. The stimulator will induce
tDCS with an intensity of 2.0 mA. The control group receives sham, for which
the stimulator will be gradually turned off after 30 seconds.

Participants will receive real-tDCS or sham twice daily for 13 min with an
interval of 20 min for three days. At baseline (before the tDCS intervention)
and a day after the days of treatment participants complete a number of
questionnaires and psychological tasks during which event-related potentials
will be recorded. Furthermore, after three months participants are asked to
return to the Erasmus Behavioral Lab for the same procedure. As a consequence,
the experiment takes two hours on the first treatment day, and one hour on the
other 4 days.

Furthermore, for three weeks, starting the week before tDCS treatment,
participants are asked to log every cigarette before they smoke one. During
these weeks, participants also complete EMA questionnaires about cigarette
consumption, craving, and affect that will take approximately 10 minutes. The
EMA questionnaire will be presented four times daily on a quasi-random basis.
Finally, during end-of-day and morning assessments participants have the
possibility to indicate any missed cigarettes. At three months follow-up,
participants are asked to undergo the same EMA procedure for one more week, to
study the lasting effects of tDCS.

Adverse effects of tDCS may be tingling and itching sensations under the
electrodes, headache, and tiredness.. However, customarily applied tDCS
protocols do not induce structural or functional damage, and are well
tolerated. Participants may however benefit from the tDCS treatment in reducing
craving and cigarette consumption.