Accepted Manuscript

Transcranial Direct Current Brain Stimulation Decreases Impulsivity in ADHD

Cheyenne Allenby, Mary Falcone, Leah Bernardo, Paul Wileyto, Anthony Rostain,
J.Russell Ramsay, Caryn Lerman, James Loughead

PII: S1935-861X(18)30138-4
DOI: 10.1016/j.brs.2018.04.016
Reference: BRS 1242

To appear in: Brain Stimulation

Received Date: 13 September 2017

Revised Date: 21 February 2018
Accepted Date: 19 April 2018

Please cite this article as: Allenby C, Falcone M, Bernardo L, Wileyto P, Rostain A, Ramsay JR, Lerman
C, Loughead J, Transcranial Direct Current Brain Stimulation Decreases Impulsivity in ADHD, Brain
Stimulation (2018), doi: 10.1016/j.brs.2018.04.016.

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Transcranial Direct Current Brain Stimulation Decreases Impulsivity in ADHD

Cheyenne Allenbya, Mary Falconea, Leah Bernardoa, Paul Wileytob, Anthony Rostainc, J.Russell
Ramsayc, Caryn Lermana, James Lougheada

Affiliations:
a. Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry,

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University of Pennsylvania, Philadelphia, PA, USA

b. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA

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c. Adult ADHD Treatment and Research Program, University of Pennsylvania, Philadelphia,

PA, USA

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Corresponding Author:

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James Loughead
Center for Interdisciplinary Research on Nicotine Addiction
University of Pennsylvania
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3535 Market Street, Suite 4100
Philadelphia, PA 19104
Phone: 215-746-7279
Email: [email protected]
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Abstract

Background: Impulsivity is a core deficit in attention deficit hyperactivity disorder (ADHD).

Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has

been shown to modulate cognitive control circuits and could enhance DLPFC activity, leading to

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improved impulse control in ADHD.

Objective/Hypothesis: We predicted 2.0 mA anodal stimulation (tDCS) versus sham

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stimulation applied over the left DLPFC would improve Conners Continuous Performance Task

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(CPT) scores. Our secondary hypothesis predicted that stop signal task (SST) reaction time

would decrease with tDCS (versus sham).

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Methods: Thirty-seven participants completed two periods of three tDCS (or sham) sessions

two weeks apart in a within-subject, double-blind, counterbalanced order. Participants

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completed the CPT and SST at the beginning of treatment (baseline), at the end of the

treatment (EOT), and at a 3-day post-stimulation follow-up.

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Results: There was a significant stimulation condition by session interaction for change in CPT
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false positives (chi-square(2)=8.75, p=0.013). This was driven primarily by a reduction CPT
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false positives at EOT (minus baseline) during the tDCS period (β=4.34, 95% Confidence

Interval (CI) 1.1 to 7.6, p=0.009). This effect did not persist at follow-up (β=2.33, p>0.05). There
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was no significant change in CPT false negative errors or hit response time (ps>0.02) or SST

reaction time (p>0.05).

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Conclusion: These findings suggest that stimulation of the left DLPFC with tDCS can improve
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impulsivity symptoms in ADHD, supporting the therapeutic potential for tDCS in adult ADHD

patients.

Keywords: Attention deficit hyperactivity disorder, tDCS, impulsivity, dorsolateral prefrontal

cortex, continuous performance task

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Introduction

Attention Deficit Hyperactivity Disorder (ADHD) is a disease characterized by symptoms of

impulsivity, inattention, and hyperactivity that emerge in childhood. In up to 60% of cases, these

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symptoms persist into adulthood and can lead to poorer life outcomes in areas such as

employment and interpersonal relationships [1]. Current pharmacological treatments include

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stimulants such as methylphenidate and amphetamine, and non-stimulant medications such as

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atomoxetine [2]. These medications can significantly improve ADHD symptoms and life outcomes.

For example, in adults with ADHD, pharmacologic treatment for more than two years is associated

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with improved ADHD symptoms and mental health functioning compared to treatment for two years

or less [3]. There is substantial variation in response and dosages must be individually titrated to
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minimize adverse effects while maintaining efficacy [2] and for more than 50% of adult ADHD

patients pharmacotherapy alone is not sufficient treatment [4]. In addition, the long-term risk/benefit
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profile of these treatments is uncertain. There remains a need for novel treatments for adult ADHD.
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Impulsivity is a core symptom of ADHD and may result from impaired cognitive control

networks [5]. These deficits can be particularly difficult for adults diagnosed with ADHD, as they
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are associated with poor occupational outcome and difficulty in maintaining relationships [6-8].

Tests of sustained attention utilized in the neuropsychological assessment of ADHD also provide a
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measure of impulsivity. False positive errors (i.e., response to a non-target stimulus) on the
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Conners Continuous Performance Test (CPT; [9]) are associated with diagnostic criteria for

impulsivity [10, 11]. Adults with ADHD make more false positive errors and these errors are among

the most sensitive measures to discriminate patients from non-ADHD samples [12-14]. Stimulant

medications such as methylphenidate decrease false positive error rates following three weeks of

treatment, with a medium-to-large effect size (η2=.21) [15]. Neuroimaging studies in healthy

subjects and ADHD subjects have linked cognitive deficits and impulsive decision-making with
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reduced activity in brain regions sub-serving the cognitive control network [16-19]. A meta-analysis

of 55 whole-brain fMRI studies showed significant hypoactivation in ADHD patients relative to

controls in bilateral attention networks, including the dorsolateral prefrontal cortex [20]. When

performing a response inhibition task, adolescent ADHD patients demonstrated reduced activation

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in the DLPFC compared to healthy controls [21]. Enhancement of the brain’s executive control

network, including the DLPFC, may increase control over impulsive responding [22, 23].

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Emerging evidence shows that activity in the in the prefrontal cortex and cognitive control

circuits can be modulated using noninvasive direct current transcranial stimulation (tDCS) [24,

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25]. TDCS treatment consists of a weak electric current (1-2 mA) applied to the scalp through

conductive electrodes [26]. A single session of tDCS targeting the left DLPFC has been shown to
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improve memory, planning ability, inhibitory control, and neural efficiency during cognitive

processing with minimal side effects [27-29]. While most studies have reported positive results
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for cognitive enhancement, studies investigating tDCS treatment specifically for ADHD are
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limited. In a study of adolescent ADHD patients, tDCS over the left DLPFC with simultaneous fMRI
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during the N-back task revealed that tDCS led to greater activation of the working memory network,

including the left DLPFC [30]. A second study of adolescents found that 5 days of anodal tDCS
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over the left DLPFC caused a significant reduction in inattention and impulsivity at end of

treatment and 7 days post stimulation [31]. In adults, anodal tDCS to the right DLPFC resulted
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in improved inattention scores [32] and anodal tDCS over the inferior frontal gyrus reported that
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tDCS treatment reduced false positive errors on an interference task in male adolescents with

ADHD [33]. However, tDCS applied over the left DLPFC in adults with ADHD did not reveal

significant differences on a go/no go task following one stimulation session [34]. Research

suggests that combining tDCS with a task that engages the targeted brain regions may result in

synergistic effects on tDCS induced neuroplastic changes, increase functional connectivity

between large-scale brain networks, and reduce the level of neural activity required for task
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performance (i.e., increase neural efficiency) to improve objective performance measures [35-

38]. It is therefore possible that multiple tDCS sessions with concurrent cognitive training task

(such as working memory training) could enhance DLPFC activity and lead to improved

attention and impulse control in adults with ADHD.

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We conducted a within-subject crossover study to examine whether three sessions of

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anodal 2mA tDCS applied over the left DLPFC during working memory training (versus working

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memory training with sham stimulation) would attenuate the cognitive symptoms of ADHD in

adults. We predicted 2.0 mA anodal tDCS (versus sham) applied over the left DLPFC would

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improve Conners Continuous Performance Task (CPT) scores (false positive errors, true

positive errors, and true positive response time). Our secondary hypothesis predicted that stop
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signal task (SST) reaction time, a measure of response inhibition, would decrease with tDCS

(versus sham).
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Materials and Methods

Participants: Adults between the ages of 18 and 65 with a prior diagnosis of ADHD were

identified through referrals from the University of Pennsylvania’s Adult ADHD Treatment &

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Research Program or recruited by mass media. ADHD diagnosis was confirmed by an

experienced clinician using a brief medical history interview and the Structured Clinical Interview

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for DSM-V (SCID-V; [39]). Individuals who met criteria for DSM-V Axis I psychiatric or substance

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disorders (except nicotine dependence) on the SCID-V and those taking psychotropic

medications (other than stimulant medications for ADHD) were excluded. Additional exclusion

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criteria were: pregnancy, planned pregnancy or breastfeeding; tDCS application contraindication

(e.g. metallic implants in the head or history of seizure); estimated IQ <90 on Shipley Institute of
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Living Scale [40]; and any impairment that would prevent task performance. Prior to each

session, participants completed a urine drug screen, pregnancy screen (women only), and
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provided exhaled carbon monoxide (smokers only) and breath alcohol content measures. All
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participants provided consent. All procedures were approved by the University of Pennsylvania
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Institutional Review Board and carried out in accordance with the Declaration of Helsinki.
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Overview of procedures: This study utilized a within-subject, cross-over design consisting of

two treatment periods: active 2mA tDCS and sham. Periods were separated by a two-week
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washout and period order was randomized, double-blind and counterbalanced. During each
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period, participants attended four visits: three stimulation visits on days one, three, and five, and

a follow-up visit on day eight. On days one, three, and five, participants received twenty

minutes of stimulation (tDCS or sham) while concurrently performing a working memory training

task (see below). Computerized cognitive assessment was performed just prior to the first tDCS

(or sham) session (baseline), immediately following the final tDCS (or sham) session (end of
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treatment), and at a 3 days post treatment follow-up session. Participants missing more than

one treatment session were withdrawn (n = 4), leaving a final sample of 37.

tDCS Treatment: A neuroConn DC-Stimulator Plus delivered a constant direct current via two

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5cm × 5cm electrodes covered in saline-soaked sponges. Electrode placement used the

international 10-20 system developed for EEG [41]. The anodal electrode was placed at F3 for

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stimulation over the left DLPFC and the cathode was placed over the right supra-orbital area.

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During the active condition, current was ramped up over 30 seconds until 2.0 mA was reached,

maintained for 19 minutes and ramped down over 30s at the end of stimulation (total stimulation

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period 20 min). For the sham treatment session, current was ramped up over 30 seconds until

2mA was reached and then immediately ramped down over 30 seconds at the beginning and
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end of a 20 minute period to mimic the skin sensations experienced during tDCS [42].
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Concurrent tDCS Task: While receiving tDCS (or sham), participants performed a visual
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working memory training task [43]. Participants viewed complex geometric figures (fractals)
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under four conditions (0, 2, 3, and 4-back): in the 0-back condition, participants responded with

a button press to a specified target fractal; for the 2-back condition, participants responded if the
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current fractal was identical to the item presented two trials back; etc. Each condition was

presented three times in 20-trial blocks (33% targets; 60s). The task was synchronized with
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tDCS administration and began with a 3-minute baseline rest period to allow participants to
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become accustomed to the sensations produced by the stimulation.

Outcome Measures: The primary outcome measures were CPT false positive errors, true

positive errors, and true positive response time. The secondary outcome measure was stop

signal reaction time (SSRT).

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Cognitive Assessment: Participants completed a computerized cognitive assessment battery

at baseline, end of treatment (EOT), and at a follow-up session 3 days post-treatment.

Conners Continuous Performance Task (CPT): The Conners CPT is a validated measure of

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sustained attention [9]. In this task, participants were shown a series of stimuli (letters) on a

computer screen and were asked to press the spacebar in response to target stimuli, but to

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withhold responding to other stimuli. The task outcomes are false positive errors (commission

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errors) and true positive errors (omission errors), as well as true positive response time. (Task

duration: ~14 min).

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Stop Signal Task (SST): The SST is a measure of response inhibition (i.e., the ability to inhibit a
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prepotent response) [44]. All trials consisted of a 500-ms warning stimulus followed by a 1,000-

ms go signal (left- or right-facing arrow) and 1,000-ms intertrial interval blank screen.
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Participants were instructed to press labeled keyboard keys as quickly and as accurately as
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possible to indicate the direction the arrow faced. Following a 32-trial practice, stop signals (an
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800-Hz, 100-ms, 70-dB tone) were presented on 25% of trials for three task blocks of 64 trials

each. The initial stop delay in each block was 250 ms and adjusted by 50 ms increments
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depending on whether the participant was able to successfully inhibit a response [45]. Mean RT

for each block was calculated based on valid responses (i.e., RT greater than 200 ms), and only
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blocks with 20–80% inhibition and at least 80% accuracy were analyzed. SST reaction time
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(SSRT) was calculated by subtracting the mean stop delay from the mean RT on go-trials (Task

duration: ~10 minutes).

tDCS Side Effects: Side effects of tDCS were assessed at the end of each tDCS (or sham)

session using the tDCS Effects Questionnaire [46]. This questionnaire asks participants to
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indicate to what extent they experienced symptoms both during and after tDCS administration

using an 11-point Likert-like scale (0 = “None” to 10 = “Severe”).

Analysis: Descriptive statistics were obtained for all variables. Change scores were calculated

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for outcome measures (end of treatment minus baseline, follow-up minus baseline) and used in

all subsequent analyses. Stimulation condition (tDCS vs. sham) by session (baseline to end of

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treatment vs. baseline to follow-up) interaction effects on primary outcomes were analyzed

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using separate linear mixed effects models with subject-level random effects, which were

estimated using maximum likelihood techniques (Stata xtreg; StataCorporation, College Station,

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TX, USA). Education level (high school/some college versus college grad), period order (tDCS

first vs. sham first), sex, age, and current medication usage were included as covariates in the
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multiple regression models. An adjusted alpha of 0.02 to correct for multiple hypothesis testing,

based on 3 primary outcome measures with an average correlation of r=0.22 [47]. Similar
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models were used to examine the secondary outcome (SSRT).

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Results

Descriptive data: Thirty-seven participants completed both study periods and thirty-five

participants attended all sessions. The sample was predominantly male (n=26, 70.1%), and

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white (n=29, 78.4%). Approximately half the sample completed high school or some college

(n=18, 48.6%). The mean age was 31.7 years old. At intake, 17 participants reported taking

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stimulant medication to treat their ADHD. There were no differences in age, gender, or

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education level between participants on and off medication.

Primary Outcome: There was a significant stimulation condition by session interaction for CPT

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false positive scores (chi-square(2)=8.75, p=0.013; Figure 1) driven primarily by the EOT
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session during active tDCS (β=4.34, 95% Confidence Interval (CI) 1.1 to 7.6, p=0.009). This

effect did not persist at follow-up (β=2.33, p>0.05). There was no significant stimulation
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condition by session interaction effect on change in CPT true positive errors or true positive
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response time (p>0.05).

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Secondary Outcome: There was no significant stimulation condition by session interaction for
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change in SSRT (p>0.05).

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Concurrent tDCS Task Performance: There was no significant stimulation condition by

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session interaction for true positives or true positive response time at any working memory load

on the N-back task (p>0.05).

Side Effects: There were significant differences in reported side effects during stimulation in the

tDCS period compared to sham for burning, itching, and tingling (Table 1). However, there were
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no differences in reported side effects following the stimulation. Participants were able to

correctly identify active tDCS stimulation during period 1 and period 2 (OR=8.56, P<0.0001).

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Discussion

Consistent with our primary hypothesis, we found that three active anodal treatment

sessions over the left DLPFC (with cathodal stimulation over the right supra-orbital area)

significantly improved performance on a measure of impulsivity in an adult ADHD population.

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Participants in this within-subject cross-over study showed significant reductions in false positive

errors on the Conners CPT during the tDCS period compared to sham at the EOT time point.

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However, these effects were not present at follow-up conducted three days after the final

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stimulation session. The improvement in performance following tDCS (versus sham) observed

in the current study (d=.6) is similar to effect sizes previously noted for methylphenidate on false

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positive errors [15, 48]. This suggests that repeated tDCS may be a novel treatment for

impulsivity in ADHD, though additional research is necessary to determine whether an

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optimized treatment approach could induce persistent effects.

Impulsivity is a core deficit in adult ADHD, and is one of the primary diagnostic criteria
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[5]. Impulsive behaviors such as blurting out answers without thinking, having difficulty awaiting
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a turn, or interrupting others can lead to poor occupational performance and difficulty in
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maintaining relationships [6]. The Conners CPT task is considered a gold standard of measuring

ADHD symptoms such as impulsivity and sustained attention [9]. Specifically, false positive
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errors on the CPT task provide a continuous quantitative measure that can effectively

distinguish ADHD patients versus healthy controls and has been associated with genetic factors
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that are also associated with ADHD [12, 13, 49]. False positive errors are thought to reflect
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impulsivity, whereas true positive errors reflect symptoms of inattention; a decrease in false

positive errors on the CPT may reflect reduced impulsivity symptoms in ADHD patients [10, 11,

13]. False positive errors in children with ADHD were found to be positively correlated with

parental ratings of impulsive behavior [50]. This pattern provides support for a model of poor

cognitive control contributing to underactive behavioral inhibition and increased impulsivity in

adults with ADHD [51]. In a study conducted by Boonstra et al., methylphenidate treatment
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resulted in a significant decrease in false positive errors [15]. Furthermore, this study found that

the decrease in false positive errors during the medication phase compared to placebo provided

a moderate predictive value for clinical response to treatment; positive predictive power of the

decrease in false positive errors on medication response was 78%. In addition, associations

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have been identified between false positive errors and the dopamine receptor D2 gene (DRD2;

rs207654, rs1079596), which may contribute to the pathology of ADHD [49].

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Although the precise mechanisms underlying the effects we observed were not tested in this

study, we propose that tDCS treatment targeting the DLPFC network may enhance top-down

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control by enhancing DLPFC activity, as frontal dysfunction in ADHD patients may be involved

in generating impulsive behavior [52, 53]. The DLPFC is a crucial site for dopaminergic effects
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on cognitive function, and current stimulant treatments for ADHD rely on increases in

dopaminergic activity to improve ADHD symptomology [54-56]. It is possible that modulation of

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DLPFC activity increases the level of inhibitory control over impulsive behaviors [57]. Therefore,
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novel treatments that enhance DLPFC activity and reduce impulsivity may be beneficial for
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ADHD patients.
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Our findings are consistent with previous reports that tDCS may be beneficial for ADHD and

other conditions marked by deficits in cognitive control, such as addiction and obesity. A recent
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meta-analysis of studies utilizing tDCS or repetitive transcranial magnetic stimulation (rTMS)

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found that stimulation of the DLPFC reduced craving for nicotine, alcohol, and marijuana in

addicted individuals, and reduced craving for food in subjects who normally experienced strong

food cravings [58]. High definition tDCS stimulation over the left DLPFC specifically was found

to reduce subject impulsivity on an intertemporal choice task, another measure of impulsive

behavior [59]. Indeed, multiple studies targeting regions involved in executive control functions

have observed improvements in cognitive deficits that characterize ADHD, such as impulsive
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responding, memory, and planning, and have shown increases in brain connectivity and neural

efficiency following treatment [60-62]. For example, anodal tDCS over the left DLPFC with

contralateral cathodal tDCS resulted in more cautious decision-making behavior [63]. Boggio et

al. reported that active anodal stimulation to the DLPFC (compared to sham stimulation)

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enhanced inhibitory responses in a go/no-go task [64]. Differences in paradigms, such as

differences in stimulation amplitude or lack of training task, may explain why some studies have

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failed to find an effect of tDCS targeting the DLPFC on impulsivity [34].

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CPT false positive errors were unrelated to working memory and SST performance

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outcomes, suggesting that CPT false positive errors may assess a specific component of

impulsivity in ADHD patients (Pearson’s r for false positives vs: N-back true positive count r=-
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0.11, p=0.19; N-back true positive reaction time r=0.08, p=0.54; SSRT r=-0.02, p=0.81). Lack of

treatment response in the SSRT is not unexpected; previous studies have found smaller
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methylphenidate effects on SSRT [15]. This may be due to differences in the nature of the
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auditory stop signal used in the SST compared to visual signals like those in the CPT, or even
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differences in neural systems underlying the SST compared to other response inhibition tasks

[52]. The go/no-go task is similar to the CPT in that the visual cue indicates when a participant
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should act or not, so that participants must restrain a primed action. In comparison, the SST

presents an auditory stop cue after the visual go cue has been presented; therefore, participants
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are required to cancel an action that has already begun. In direct comparisons of generic stop
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signal tasks and go/no-go, tasks increased BOLD signal was observed in left DLPFC, medial,

and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal

specialization for response selection [65]. Performance on the go/no-go is not associated with

SST performance in children with ADHD [66], and in adults, tDCS treatment targeting the left

DLPFC increased the proportion of correct responses in the “go stage” of the go/no-go test

compared to sham [67]. It is possible that impulsivity consists of multiple components, and
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component-specific assessment of impulse control in healthy participants has revealed different

activation patterns of the neural impulse control network [68, 69]. Therefore, the absence of

tDCS effects on other CPT outcomes, such as true positive errors and reaction time, may be

due to differences in inhibitory processes for false positive versus true positive errors. Similar to

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studies using methylphenidate, there was no effect of tDCS treatment on overall mean CPT

reaction time, and correlation studies suggest that mean reaction time is minimally related to

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ADHD symptoms as a whole [15, 50].

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Our sample of 37 individuals provided 80% power to detect an effect size of d ≈ 0.6, similar

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to effect sizes seen for methylphenidate treatment in adult ADHD, and the inclusion of ~30%

women is representative of the general ADHD population. Strengths of our paradigm include the
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within-subject design, multiple stimulation sessions, and the use of a concurrent working

memory training task during stimulation. A limitation of this study is the lack of CPT performance
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data immediately following stimulation at Session 1. Because our outcomes were not assessed
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after Session 1, we cannot be certain that treatment effect on false positive errors was a
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cumulative effect of three stimulation sessions, rather than an acute effect of stimulation at

Session 3. However, multiple tDCS sessions have been shown to produce a cumulative
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increase in cortical excitability, and combining tDCS with a training task over time may result in

greater gain on a non-trained test than tDCS alone [70, 71]. Sham stimulation may not be the
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optimal method for blinding participants during tDCS treatment [72, 73]. As a contribution to this
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discussion, we found that our participants were able to correctly identify tDCS during period 1

and period 2 (OR=8.56, P<0.0001). This may be related to the significant differences in side

effects ratings between conditions; although side effects in both conditions were generally mild

(rated <3 out of 10), participants endorsed higher ratings during the tDCS condition compared to

sham (Table 1). Another potential limitation is that our sample included participants who were

taking stimulant medications as well as those who were not. However, medication status was
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included as a covariate and did not significantly predict outcomes. Additionally, approximately

half of our participants met criteria for the primarily inattentive subtype of ADHD, and half met

criteria for the combined inattentive and hyperactive/impulsive subtype. Medication status and

ADHD subtype may influence performance and task-related brain activation on attention and

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response inhibition tasks [52, 74]. Sample size was not sufficiently powered to test for condition

by medication or condition by subtype interaction effects; however, our within subject design (in

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which each participant serves as his or her own control) reduces the chances that our results

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are confounded by medication status or ADHD subtype. Further research is needed to

determine whether tDCS effects differ across ADHD subtypes or by medication usage.

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Our findings that active anodal tDCS over the left DLPFC with cathodal tDCS over the

right supra-orbital area significantly decreased false positive errors in the Conners CPT
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suggests that tDCS may offer promise as a novel treatment for impulsivity in ADHD. This

treatment was well tolerated; reported side effects were mild and subsided immediately
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following tDCS administration. Future studies employing different standardized training tasks
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(such as ones more specific response inhibition) may be useful in order to optimize outcomes.

Furthermore, repeated dose administration over a longer time period may provide more
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persistent performance outcomes following treatment. These data support advancing to a larger

study to optimize treatment course for more durable potential benefits.

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Conflicts of Interest

None

Funding source

This research was supported by a gift from Robert and Judy Levine; and [training grant funding].

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The funding source had no role in the study design, collection, analysis or interpretation of the

data, writing the manuscript, or the decision to submit the article for publication.

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Acknowledgments

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We thank Lofton Harris and Dr. Anita Hole for sharing their clinical expertise; Dr. Mario

Cristancho for his support as study physician; Dr. Roy Hamilton for advice and tDCS training;

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and Dr. Rebecca Ashare for study support. AN
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Table 1: Cognitive Task Performance Outcomes

tDCS Sham
CPT False Positive Error (Primary) Mean SEM Mean SEM
Baseline 21.5 1.9 19.8 1.9
End of Treatment 17.1 1.5 19.8 1.8
Follow-up 20.2 2.0 19.8 2.2

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CPT True Positive Error
Baseline 2.0 0.8 2.4 0.8
End of Treatment 1.9 0.7 2.1 0.4

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Follow-up 1.0 0.3 1.3 0.4
CPT Response Time

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Baseline 416.7 12.2 422.6 12.2
End of Treatment 420.9 10.4 419.7 12.0
Follow-up 407.2 10.3 411.9 12.7
SST Reaction Time

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Baseline 284.3 11.0 300.8 11.3
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End of Treatment 288.4 12.5 291.5 11.2
Follow-up 268.1 9.3 267.6 11.0
N-back True Positive Response Count
Baseline 45.5 1.1 43.5 1.5
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End of Treatment 43.3 1.3 44.9 1.4

Follow-up 46.0 1.3 47.6 1.7
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N-back True Positive Response Time

Baseline 727.9 24.1 725.4 29.3
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End of Treatment 744.1 26.0 744.6 29.5

Follow-up 709.1 23.8 715.6 27.1
N-back False Positive Count
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Baseline 20.6 1.9 19.5 2.5

End of Treatment 13.9 1.6 14.8 2.2
Follow-up 16.9 1.9 17.1 2.5
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N-back False Positive Reaction Time

Baseline 955.0 55.6 955.9 49.0
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End of Treatment 1021.9 49.0 984.1 53.3

Follow-up 982.4 44.8 1016.9 48.6

Table 1 Caption: Stimulation condition by session interaction is significant for CPT false

positive errors only (p<0.001). There were no significant differences by condition in baseline

performance measures.
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Table 1. Mean Ratings for Side Effects Reported during tDCS

Side effect during Sham M(SD) tDCS M(SD)

tDCS
Tingling 1.4(1.4) 1.9(1.4)*
Itching Sensation 1.8(1.3) 1.1 (1.3)*

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Burning Sensation 1.5 (2.0) 2.8 (2.0)*
Pain 0.2(0.4) 0.5(0.7)*
Fatigue 1.3(1.9) 1.4(1.8)
Nervousness 0.2(0.4) 0.3(0.8)

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Difficulty 2.1(2.0) 2.0(1.9)
concentrating
Mood change 0.4(0.8) 0.5(0.8)

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Change in vision 0.2(0.6) 0.3(0.7)
Headache 0.3(0.6) 0.3(0.6)
Visual sensation 0.3(0.7) 0.6(0.8)

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Table 1 Caption: The average side effect ratings were mild. Ratings for tingling, itching
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sensation, burning sensation, and pain were significantly different between active and sham

stimulation. * p<0.05
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Figure 1 Caption: There was a significant stimulation condition by session interaction for CPT false positive
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scores (χ2 =15.44, p<0.001; Figure 1A) driven the decrease in commission errors from baseline to end of

treatment in the tDCS group (β=-0.36, 95% Confidence Interval (CI) -0.54 to -0.18, p<0.001). This effect did
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not persist at follow-up (β=-0.13, p>0.05). There was no significant stimulation condition by session interaction

effect on true positive errors or response time (p>0.05; Figure 1B-C).

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Figure 2 Caption: Medication status was a significant covariate in the overall model.
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Exploratory analysis reveals a significant condition by session interaction at end of treatment for

those currently using ADHD medication (χ2 =12.15; p<0.001) There is also a significant
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interaction at end of treatment for those currently not using ADHD medication (χ2 =4.97; p<0.03)

Overall, there is no significant condition by current medication interaction (p>0.05).

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Allenby et al manuscript (“Transcranial Direct Current Brain Stimulation Decreases Impulsivity in

ADHD”) highlights:

• We examined the treatment potential of anodal tDCS stimulation for adult ADHD.

• Three TDCS sessions reduced false positives on a continuous performance task.

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• Repeated tDCS over the left DLPFC may treat impulsivity in adult ADHD.

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AUTHOR DECLARATION
We wish to confirm that there are no known conflicts of interest associated with this
publication and there has been no significant financial support for this work that could
have influenced its outcome.

We confirm that the manuscript has been read and approved by all named authors and

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that there are no other persons who satisfied the criteria for authorship but are not listed.
We further confirm that the order of authors listed in the manuscript has been approved
by all of us.

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We confirm that we have given due consideration to the protection of intellectual
property associated with this work and that there are no impediments to publication,
including the timing of publication, with respect to intellectual property. In so doing we

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confirm that we have followed the regulations of our institutions concerning intellectual
property.

We further confirm that any aspect of the work covered in this manuscript that has

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involved either experimental animals or human patients has been conducted with the
ethical approval of all relevant bodies and that such approvals are acknowledged within
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the manuscript.

We understand that the Corresponding Author is the sole contact for the Editorial
process (including Editorial Manager and direct communications with the office). He/she
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is responsible for communicating with the other authors about progress, submissions of
revisions and final approval of proofs. We confirm that we have provided a current,
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Signed by all authors as follows:

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Cheyenne Allenby

Mary Falcone
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Leah Bernardo

Paul Wileyto
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Anthony Rostain
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J.Russell Ramsay

Caryn Lerman

James Loughead