The Effect of Transcranial Direct Current Stimulation of the Prefrontal Cortex on Antisocial and Aggressive Behavior
Phase: NA
Conditions: Antisocial Behavior, Aggression
Sponsor: University of Pennsylvania

Study Title: Stimulation of the prefrontal cortex reduces intentions to commit aggression: A 
randomized, double-blind, placebo-controlled, stratified, parallel-group trial 
 
NCT02427672 
 
IRB Approval Date: November 6, 2017 
 
 

Choy, O., Raine, A., & Hamilton, R. H. (2018). Stimulation of the prefrontal cortex reduces 
intentions to commit aggression: A randomized, double-blind, placebo-controlled, 
stratified, parallel-group trial. The Journal of Neuroscience, 38, 6505-6512. 
 
Materials and Methods 
Trial Design  
The study consisted of a double-blind, placebo-controlled, stratified, randomized trial 
comparing an anodal tDCS intervention with a sham control group. Baseline assessments and 
one session of tDCS or sham intervention were conducted during the experimental session, while 
outcome measures were assessed the following day. Tasks and questionnaires were administered 
in a fixed order. The study was approved by the Institutional Review Board of the University of 
Pennsylvania and the trial protocol was registered at ClinicalTrials.gov (NCT02427672). 
 
Participants  
Eighty-six healthy adults (≥ 18 years of age) were recruited in Philadelphia between 
April 2015 and April 2016. The experiment took place during the course of one visit to the study 
site. In addition to assessments conducted at baseline, participants were followed up one day 
after the experimental session using a web-based questionnaire. Exclusion criteria included 
contraindications to brain stimulation, including metallic implants near the electrode sites, 
unstable medical conditions, neurological, cardiovascular, or psychiatric illness, participation in 
another non-invasive brain stimulation study on the same day, history of adverse reactions to 
tDCS, and lack of email access. Written informed consent was obtained from all participants. 
 

tDCS Intervention  
tDCS was administered by trained study personnel using a battery-driven, constant-
current stimulator (TCT Research). Two anodal electrodes were placed over the DLPFC 
bilaterally (F3 and F4) according to the International 10-20 EEG system. A constant current of 
2mA (1mA to each DLPFC site) was applied for 20 minutes through saline-soaked sponge 
electrodes (5x5cm). A single extracephalic cathodal electrode (5x7cm) was placed at the 
posterior base of the neck in order to minimize unintentional effects of inhibitory stimulation on 
brain activity.  
 
Following standard tDCS protocol, stimulation commenced after a 30-second ramp-up 
period. The current was ramped down over the last 2 seconds. The tasks performed during tDCS 
are understood to influence the behavioral after-effects of stimulation (Gill et al., 2015). Thus, 
during the stimulation session, all participants performed the Psychology Experiment Building 
Language (Mueller and Piper, 2014) version of two cognitive tasks that are known to engage the 
DLPFC, the Psychomotor Vigilance Task (Dinges and Powell, 1985; Cui et al., 2015), followed 
by the Iowa Gambling Task (Bechara et al., 1994; Ernst et al., 2002). Although participants in 
both intervention arms received the same electrode placement and ramp-up/down times, 
stimulation for the sham control group was discontinued after 30 seconds. This has proven to be 
effective for blinding as participants habituate to the sensation of stimulation within seconds of 
current initiation (Gandiga et al., 2006).  
 
Intentions to commit aggression. Behavioral intentions to commit aggressive acts were 
assessed using two hypothetical vignettes, which have been studied in samples with similar 

characteristics to ours (Hannon et al., 2000; Mazerolle et al., 2003). Brief scenarios describing 
two types of aggression, physical assault and sexual assault, were presented to participants who 
responded to the anticipated likelihood that they would commit the aggressive act. Responses 
were measured on a scale ranging from zero (no chance at all) to ten (100 percent chance).  
 
Perceptions of moral wrongfulness. To assess moral perceptions of the aggressive acts, 
participants were asked to rate how morally wrong it would be to act as the protagonist in the 
scenario on a scale from 0 (not at all) to 10 (very). Aggregate measures of aggressive intent and 
perception of moral wrongfulness were created by combining responses from the physical and 
sexual assault scenarios (Armstrong and Boutwell, 2012). 
 
Aggression. The voodoo doll task is a reliable and validated behavioral analog measure 
of aggression (DeWall et al., 2013). In this task, participants were shown a computer-based 
image of a doll that represented a partner or a close friend. They were told that they were given 
the opportunity to release their negative energy to that individual by inserting as many pins (0-
51) in the doll as they wished. Instructions did not use the word “voodoo”. Stabbing the doll with 
more pins indicated higher levels of aggression.  
 
Randomization and Stratification 
At the initial visit, participants were randomized into an active stimulation or 
sham/placebo condition using a computerized urn randomization procedure (Stout et al., 1994). 
The stratification factors were age (18 years/19 years/20 years and above), sex (male/female), 

and ethnicity (Caucasian/non-Caucasian). This stratification was used to balance groups on key 
demographic variables. 
 
Blinding  
Participants and experimenters were blind to the tDCS condition assignment. The trial 
adhered to established procedures to maintain separation between staff that conducted the 
stimulation and staff that engaged with the participant. In each experimental session, only one 
experimenter who set up the tDCS procedure had knowledge of the participant’s allocation. To 
further ensure blinding, all participants were kept blind to the objective of the study and outcome 
measures were not taken in the presence of research staff as they could lead to biased results.  
 
In the 3 cases where double blinding was compromised due to the inability of having 
more than one experimenter at a session, the cases were excluded from analyses. To assess 
adherence to blinding procedures, James’ (James et al., 1996) and Bangs’ (Bang et al., 2004) 
blinding indices were calculated using the participants’ and blinded experimenters’ guesses 
about group assignment at the end of the experimental session. 
 
Statistical Analysis Plan 
One-way ANCOVA was used to test group differences in intentions to commit 
aggression and the behavioral measure of aggression. Baseline measures were examined as 
possible covariates: variety of crime throughout the lifetime, aggression, GPA, trait anxiety, 
social adversity, psychopathy, the lack of premeditation and sensation-seeking dimensions of 
impulsivity, and self-control. 

In addition to a Self-Report Crime Questionnaire that asked participants to indicate the 
number of times they had committed 36 criminal and delinquent acts ranging from white-collar 
and blue-collar offenses (e.g. fraud and shoplifting) to non-criminal, deceptive behaviors (e.g., 
cheating on an exam), participants’ baseline levels of aggression were assessed using the 
Reactive-Proactive Aggression Questionnaire (Raine et al., 2006). Trait anxiety was assessed 
using the 20-item Spielberger State-Trait Anxiety Inventory (Spielberger, 1983). A social 
adversity index was obtained based on responses to 14 items obtained from demographic 
questionnaires. Items included parent unemployment, mother’s low education, father’s low 
education, parental separation or divorce, placement in a foster home, hospital, or other 
institution during childhood, having 5 or more siblings, born to a teenage mother, a ratio of 
people per room (including bedrooms, living room, dining room, and kitchen) of 1.0 and above, 
brought up in public housing, parents’ use of welfare or food stamps from the government, father 
or mother had been arrested, father or mother has had problems with alcohol or drugs, father or 
mother has had physical illness, such as heart or lung problems, father or mother has had mental 
illness, such as alcoholism, major depression, schizophrenia, or anxiety. To assess psychopathic 
traits, the short form of the Self-Report of Psychopathy-III (SRP-SF) questionnaire, comprising 
29 items, was administered (Paulhus et al., 2009). Additionally, scores were obtained from the 
lack of premeditation and sensation-seeking subscales of the short-form version of the UPPS-P 
Impulsivity Scale (SUPPS-P) (Lynam, 2013), and self-control was assessed using the 13-item 
Brief Self-Control Scale (Tangney et al., 2004).  
 
Following recommendations, stratification variables and baseline measures that were 
associated with the outcomes were adjusted for, while variables with baseline imbalances were 

not (Committee for Proprietary Medicinal Products, 2004; Kahan et al., 2014). Effect sizes were 
calculated using partial eta squared.  
 
To provide information on a mechanism of action accounting for any effect of tDCS on 
aggressive intent, change in perceptions of moral wrongfulness was examined using ANCOVA. 
We tested whether enhanced moral judgment mediated group differences in intent to commit 
aggressive acts through a bootstrapping approach using the PROCESS macro on SPSS (Hayes, 
2013). 10,000 bootstrapped samples were drawn from the original data. The indirect effect of 
tDCS on intent to commit aggression was calculated as the product of the regression coefficients 
for the relationship between tDCS and moral judgment and the association between moral 
judgment and aggressive intent. The percent mediated, PM, is expressed as the ratio of the 
indirect to total effect of treatment group on intention to commit aggression (Ditlevsen et al., 
2005; Hayes, 2013). Hypothesis tests were two-tailed. Blinding indices were obtained using 
STATA version 14.0 (Stata Corp, 2015). All other statistical analyses were conducted using 
SPSS version 24.0 (IBM Corp, 2016).