Measuring Cortical Dynamics of Inhibitory Control Before, During and After Transcranial Direct Current Stimulation (tDCS)
Phase: NA
Conditions: Impulsive Behavior
Sponsor: Najat Khalifa

 
 
 
Page 1 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
 
 
Measuring cortical dynamics of inhibitory control before, during, 
and after transcranial Direct Current Stimulation (tDCS). 
 
Draft 1 / Final Version 1.0 
08.01.2018 
 
 
 
Short title:  
 
tDCS and Inhibitory Control 
 
 
Acronym:   
 
N/A 
 
 
IRAS Project ID: 
N/A 
 
 
Study Sponsor:  
University of Nottingham 
 
 
Sponsor reference: 
insert when allocated 
 
 
Funding Source: 
Medical Research Council (Nottingham 
Confidence in Concept, School of Medicine). 

 
 
 
Page 2 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
STUDY PERSONNEL AND CONTACT DETAILS 
 
Sponsor: 
University of Nottingham 
Contact name 
Ms Angela Shone 
 
Head of Research Governance 
 
Research and Graduate Services 
 
King’s Meadow Campus 
 
Lenton Lane 
 
Nottingham 
 
NG7 2NR 
 
Chief investigator:  
Dr Najat Khalifa, Associate Professor and Consultant 
Forensic Psychiatrist (Division of Psychiatry and 
Applied Psychology), Room B20, Institute of Mental 
Health. University of Nottingham, Innovations Park, 
Triumph Road, Nottingham, NG7 2TU.  
TEL: 01158231269 E-mail: 
najat.khalifa@nottingham.ac.uk  
 
Co-investigators:  
Dr George O’Neill (post-doctoral fellow)  
 
Room 23, Sir Peter Mansfield Imaging Centre 
 
University Park 
 
Nottingham, NG7 2RD 
 
TEL: 0115 846 7774, E-mail: 
george.oneill@nottingham.ac.uk 
 
 
 
Dr Lauren Gascoyne (post-doctoral fellow):  
Room 23, Sir Peter Mansfield Imaging Centre 
 
University Park 
 
Nottingham, NG7 2RD 
 
TEL: 0115 846 7774, E-mail: 
Lauren.gascoyne@nottingham.ac.uk.  
 
 
Christian Sales (Assistant Psychologist). Institute of 
Mental Health. University of Nottingham, Jubilee 
Innovation Park, Triumph Road, Nottingham, NG7 
2TU. E-mail: Christian.sales@nottingham.ac.uk.   
 
Dr Katy Jones, Assistant Professor of Applied 
Psychology (Division of Psychiatry and Applied 
Psychology), Room C24, Institute of Mental Health. 
University of Nottingham, Jubilee Innovation Park 
Triumph Road, Nottingham, NG7 2TU 
TEL: 0115 82 30418 E-mail: 
katy.jones@nottingham.ac.uk 
 
Professor Peter Liddle, Professor of Psychiatry 
(Division of Psychiatry and Applied Psychology), 
Room B25, Institute of Mental Health, University of 

 
 
 
Page 3 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Nottingham, Jubilee Innovation Park, Triumph Road, 
Nottingham, NG7 2TU.  
TEL: 0115 82 30421 E-mail: 
peter.liddle@nottingham.ac.uk  
 
Dr Matt Brookes (School of Physics and Astronomy), 
Associate Professor, Room MR02 Sir Peter 
Mansfield Imaging Centre 
University Park, Nottingham, NG7 2RD. 
TEL: 0115 951 5166 E-mail: 
matthew.brookes@nottingham.ac.uk  
 
Study Statistician: 
N/A 
 
Study Coordinating Centre:  Division of Psychiatry and Applied Psychology and 
School of Physics and Astronomy.  
 
 

 
 
 
Page 4 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SYNOPSIS 
 
Title 
Measuring cortical dynamics of inhibitory control before, during, and after 
transcranial direct-current stimulation (tDCS). 
Acronym 
N/A 
Short title 
tDCS and Inhibitory Control 
Chief Investigator 
Dr Najat Khalifa 
Objectives 
To further our understanding of the neurobiological mechanisms 
underpinning Rapid Response Impulsivity and how these can be 
influenced by tDCS, we aim to examine the influence of anodal tDCS on 
beta-band and alpha-band oscillatory activities, using an anti-saccade 
task administered before, during and after tDCS stimulation.  
 
We hypothesise that: 
(i) 
a generalised mechanism for top-down inhibitory control will 
play a vital role, whereby prefrontal beta-band activity initiates 
alpha-band activity for functional inhibition over the frontal 
eye fields and other areas in the neuro-circuitry involved in 
RRI 
(ii) 
anodal tDCS (as opposed to sham) delivered over the right 
DLPFC will enhance this mechanism; and  
(iii) 
there will be no significant correlations between measures of 
self-report impulsivity and performance on the anti-saccade 
task and measures of oscillatory activity.  
 
Study Configuration 
Single session, healthy controls, proof of concept, MEG, tDCS, 
Impulsivity. 
Setting 
Sir Peter Mansfield Imaging Centre, University Park, University of 
Nottingham.  
Sample size estimate 
Up to 60 participants will be sought. This is based on a power calculation 
using an independent-sample t-test (G*Power; Faul et al., 2007). This 
yielded a total sample size of 60 participants, with an effect size of d = 
0.65, 80% power and alpha error probability of α = 0.05 (one tailed 
testing). 
 
Number of participants 
Up to 60 healthy controls 
Eligibility criteria 
Aged 18-40, studying or working at UoN, no history of epilepsy or other 
neurological conditions, significant head injury, substance misuse, major 
mental disorder, or those currently receiving psychotropic medication. 
Description of 
interventions 
tDCS. Study will also involve brain imaging (MEG and MRI). 

 
 
 
Page 5 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Duration of study 
12 months 
Methods of analysis  
Analysis of beta and alpha band MEG data will follow Hwang et al 
(2014). Between subjects’ differences in the effects of tDCS on task 
performance will be examined using the Reaction Time and failure to 
saccade before and after stimulation. Independent samples t-test will be 
used for normally distributed data. Otherwise, the Mann-Whitney tests 
will be used. Correlational analysis will be used to examine the 
relationship between scores on UPPS-P, anti-saccade task performance 
and oscillatory activity over regions of interest. 
 

 
 
 
Page 6 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
ABBREVIATIONS  
 
 
ACC 
 
Anterior Cingulate Cortex 
CI 
 
Chief Investigator overall 
CRF 
 
Case Report Form 
DLPFC 
Dorsolateral pre-frontal cortex 
GCP 
 
Good Clinical Practice 
MEG  
Magnetoencephalography 
MRI 
 
Magnetic Resonance Imaging 
NHS 
 
National Health Service 
PI 
 
Principal Investigator at a local centre 
Pre-SMA 
Pre-Supplementary Motor Area 
PIS 
 
Participant Information Sheet 
RRI 
 
Rapid Response Impulsivity 
REC 
 
Research Ethics Committee 
R&D 
 
Research and Development department 
tDCS  
Transcranial Direct-Current Stimulation 
UPPS-P 
Urgency, Pre-meditation, Perseverance, Sensation-Seeking Questionnaire 
(Positive Urgency) 
UoN 
 
University of Nottingham 
 
 
 
 

 
 
 
Page 7 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
TABLE OF CONTENTS 
 
 
SYNOPSIS ................................................................................................................................. 4 
ABBREVIATIONS ................................................................................................................... 6 
STUDY BACKGROUND INFORMATION AND RATIONALE ....................................... 9 
STUDY OBJECTIVES AND PURPOSE ............................................................................... 9 
PURPOSE 
9 
PRIMARY OBJECTIVE 
9 
SECONDARY OBJECTIVES 
10 
TO EXAMINE STUDY FEASIBILITY INCLUDING RECRUITMENT RATE, AND 
ACCEPTABILITY OF THE STUDY PROTOCOL. ......................................................... 10 
STUDY DESIGN .................................................................................................................... 10 
STUDY CONFIGURATION 
10 
RANDOMIZATION AND BLINDING 
10 
Maintenance of randomisation codes and procedures for breaking code 
10 
STUDY MANAGEMENT 
10 
DURATION OF THE STUDY AND PARTICIPANT INVOLVEMENT 
10 
End of the Study 
10 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
10 
Recruitment 
10 
Eligibility criteria 
11 
Inclusion criteria 
11 
Exclusion criteria 
11 
Expected duration of participant participation 
12 
Participant Withdrawal 
12 
Informed consent 
12 
STUDY REGIMEN 
12 
Compliance 
13 
Criteria for terminating the study 
13 
ANALYSES ............................................................................................................................. 14 
Methods 
14 
Sample size and justification 
14 
ADVERSE EVENTS .............................................................................................................. 14 
ETHICAL AND REGULATORY ASPECTS ..................................................................... 14 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
15 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
15 
RECORDS 
16 
Case Report Forms 
16 
Source documents 
16 
Direct access to source data / documents 
16 
DATA PROTECTION 
16 
QUALITY ASSURANCE & AUDIT .................................................................................... 17 

 
 
 
Page 8 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
INSURANCE AND INDEMNITY 
17 
STUDY CONDUCT 
17 
STUDY DATA 
17 
RECORD RETENTION AND ARCHIVING 
17 
DISCONTINUATION OF THE STUDY BY THE SPONSOR 
18 
STATEMENT OF CONFIDENTIALITY 
18 
PUBLICATION AND DISSEMINATION POLICY .......................................................... 18 
USER AND PUBLIC INVOLVEMENT .............................................................................. 18 
STUDY FINANCES ............................................................................................................... 18 
Funding source 
18 
Participant stipends and payments 
19 
REFERENCES ....................................................................................................................... 19 
 

 
 
 
Page 9 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
STUDY BACKGROUND INFORMATION AND RATIONALE 
 
Rapid Response impulsivity (RRI) is a form of impulsivity characterised by failure to refrain 
from action initiation or stop an ongoing or pre-potent action. It is a common feature of many 
psychiatric disorders (e.g., conduct, antisocial personality, or substance use disorders, and 
Attention Deficit Hyperactivity Disorder, ADHD), and has been associated with serious 
consequences for individuals and others (e.g., self-harm, violence).  
 
Brain regions implicated in RRI include the prefrontal structures (particularly dorsolateral 
prefrontal cortex, DLPFC), Anterior Cingulate Cortex (ACC), pre-supplementary motor area 
(Pre-SMA) and limbic structures (Castellanos-Ryan & Séguin, 2015; Brevet-Aeby et al., 
2016). However, little is known about what specific executive function the DLPFC fulfills. A 
generalised mechanism for top-down inhibitory control has been suggested (Hwang et al, 
2014), whereby a prefrontal beta-band activity initiates alpha-band activity for functional 
inhibition of the effector system.  
 
tDCS is a non-invasive brain stimulation technique that modulates brain activity through a 
weak direct electric current which stimulates the brain area beneath the stimulation site and 
deeper structures through connected neuronal networks. tDCS has been used to modulate 
impulsivity, but firm conclusions regarding its efficacy and mechanism of action in relation to 
RRI cannot be drawn from the available literature owing to limited knowledge of the 
neurobiological underpinnings of RRI.  
 
Of importance is the integration of tDCS with multiple forms of imaging that offer 
complementary information with clinically relevant measures. If we find RRI can be 
modulated by tDCS, this has implications for working with clinical populations to reduce harm 
in the future. 
 
STUDY OBJECTIVES AND PURPOSE 
 
PURPOSE 
To further our understanding of the neurobiological mechanisms underpinning RRI and how 
these can be influenced by tDCS, we aim to examine the influence of anodal tDCS on beta-
band and alpha-band oscillatory activities, using an anti-saccade task administered before, 
during and after tDCS stimulation.  
PRIMARY OBJECTIVE 
We hypothesise that:  
i. 
a generalised mechanism for top-down inhibitory control will play a vital role, whereby 
prefrontal beta-band activity initiates alpha-band activity for functional inhibition over 
the frontal eye fields and other areas in the neuro-circuitry involved in RRI;  
ii. 
anodal tDCS (as opposed to sham) delivered over the right DLPFC will enhance this 
mechanism; and  
iii. 
there will be no significant correlations between measures of self-report impulsivity 
and performance on the anti-saccade task and measures of oscillatory activity.  
 

 
 
 
Page 10 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SECONDARY OBJECTIVES 
To examine study feasibility including recruitment rate, and acceptability of the study 
protocol.  
 
STUDY DESIGN 
 
STUDY CONFIGURATION 
This will be a single-centre, one-off study using randomisation to anodal tDCS or sham using 
a computer generated code. Participants will be blind to tDCS condition. Pre and post task 
performance will be measured to examine changed in RRI before and after tDCS. 
 
RANDOMIZATION AND BLINDING 
 
Consenting participants will be randomly allocated, using a computer generated code, to 
receive either anodal tDCS or sham. Randomization will be conducted by Dr. Elizabeth 
Liddle (Assistant Professor, Division of Psychiatry and Applied Psychology) as she is 
external to the project, but is familiar with such randomization techniques in other related 
MEG work.   
 
Maintenance of randomisation codes and procedures for breaking code 
 
The study is single blind, thus there will be no procedure for breaking code.  
 
STUDY MANAGEMENT 
The study will be conducted in line with the standards set out in the University of Nottingham 
Code of Research Conduct and Research Ethics (2016). The Chief Investigator has overall 
responsibility for the study and shall oversee all study management. The data custodian will 
be the Chief Investigator (Dr Najat Khalifa). Members of the research team will meet monthly 
to discuss the project implementation plan and the overall progress.  
 
DURATION OF THE STUDY AND PARTICIPANT INVOLVEMENT 
Study Duration: 12 months (February 18- 19) 
 
 
Participant Duration: One off session (approximately 4 hours) between February 18 and end 
of the study. 
 
End of the Study 
The end of the study will be defined as the last visit of the last recruited participant. There is 
no follow-up period. Final data analysis and write up will take place after this.  
 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
Recruitment 
The study setting will be UoN (UK campus). This setting has been chosen for convenience, 
and because healthy controls (rather than a clinical population) will be sought. 
 
All participants will be staff and students aged 18-40 at UoN. As well as general online and 
poster advertising across the university, targeted advertising will be conducted at UoN 

 
 
 
Page 11 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
societies where recreational activities are associated with a high degree of risk (e.g. speed, 
height, or high level of physical exertion). This is because, it is thought people who take part 
in such activities are more likely to have a ‘thrill-seeking’ personality (Self et al., 2007). For 
example, the following societies have been identified: UoN Gliding Club, UoN Equestrian 
Club, UoN Climbing Club, UoN Sky Diving Club, UoN Motorsport. Societies will be 
approached through e-mail, or the society social media page. As well as targeted 
recruitment, posters will be placed across the university (e.g., Student’s Union, Library). 
 
Participants will be recruited from adverts (posters and information) placed online and in 
buildings around UoN (UK campuses e.g. University Park, Jubilee). Interested participants 
can choose to take part in the study by contacting one of the researchers by e-mail or 
telephone (contact details are provided on all advertising material). 
 
After the participant has contacted the researcher, further information will be provided (brief 
explanation of the study, Participant Information Sheet and information about tDCS will be 
sent by e-mail, and researcher will review a brief safety screening questionnaire to ensure 
the participant is eligible to have tDCS and to go in the scanner). If eligible, participants will 
be booked in to attend the Sir Peter Mansfield Centre for the 4-hour appointment.  
 
On the day of the study, participants will be given a chance to ask any questions about the 
study, and their safety questionnaire will be reviewed again by the researcher before signing 
the consent form to begin the study  
 
It will be explained to the potential participant that entry into the study is entirely voluntary 
and that their withdrawal will not affected their studies or employment at UoN. It will also be 
explained that they can withdraw at any time but attempts will be made to avoid this 
occurrence. In the event of their withdrawal it will be explained that their data collected so far 
cannot be erased and we will seek consent to use the data in the final analyses where 
appropriate. 
 
N.B. Data should not be erased as it should be possible to recreate a participant’s 
participation up to their point of withdrawal. Also once data has been entered onto the UoN 
secure network, data cannot be erased as UoN backups cannot be tampered with. This is 
covered on clause 2 of the consent form and the withdrawal section of the participant 
information sheet template. 
 
Eligibility criteria 
 
Main points of consideration are: 
 
Over 18 
 
Able to give informed consent (participants will be studying or working at UoN and 
therefore will be able to read and understand English) 
 
Participant safety for tDCS or scanning (e.g., See below for exclusion criteria) 
 
Inclusion criteria 
 
Aged 18-40  
 
Studying or working at UoN  
 
Able to give informed consent 
 
Exclusion criteria 

 
 
 
Page 12 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
A tDCS safety questionnaire will be used to assess suitability for the procedure. Typical 
reasons a participant may be excluded from the study will be due to:  
 
 
History of epilepsy or other neurological conditions 
 
Significant head injury 
 
Current substance misuse 
 
Major mental disorder 
 
Currently receiving psychotropic medication. 
 
Expected duration of participant participation 
Study participants will be participating in the study for up to 4 hours.  
 
Participant Withdrawal  
Participants may withdraw from the study due to: 
 
Safety reasons (including pregnancy) 
 
Failure of participant to adhere to protocol requirements 
 
Withdrawal of consent 
 
Note that participants must be withdrawn from study if consent is withdrawn.   
Participants may be withdrawn from the study either at their own request or at the discretion 
of the Investigator. The participants will be made aware that this will not affect their future 
care. Participants will be made aware (via the Participant Information Sheet and Consent 
Form) that should they withdraw the data collected to date cannot be erased and may still be 
used in the final analysis. 
Informed consent 
All participants will provide written informed consent. The Consent Form will be signed and 
dated by the participant before they enter the study. The Investigator will explain the details 
of the study and review the Participant Information Sheet, ensuring that the participant has 
sufficient time to consider participating or not. The Investigator will answer any questions that 
the participant has concerning study participation.  
One copy of the Consent Form will be kept by the participant and one will be kept by the 
investigator. 
Should there be any subsequent amendment to the final protocol, which might affect a 
participant’s participation in the study, continuing consent will be obtained using an amended 
Consent Form which will be signed by the participant. 
Completion and subsequent return of questionnaires will be taken as informed consent and 
separate written informed consent will not be sought 
 
STUDY REGIMEN 
Pilot study 
 
Prior to the main study, a brief pilot study (up to 5 participants) will be conducted to test the 
protocol. Participants will spend up to 1 hour in MEG for the purpose of optimising 
performance of the MEG system during concurrent tDCS and MEG. 
 
Before the appointment 

 
 
 
Page 13 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
Participant sees study advert and contacts researcher by e-mail or telephone to find 
out more detail about the study (see study advert for details). 
 
Researcher supplies information to participant by telephone or e-mail (Participant 
Information Sheet and tDCS Information Sheet will be sent by e-mail at least 24 hours 
before the study). Researcher conducts tDCS and imaging screening questionnaire 
over the telephone. 
 
If eligible, researcher books participant in for the study.  
 
At the appointment 
 
 
Step 1. Researcher reviews participant information sheet with participant and 
answers any questions the participant may have about the study. Researcher 
confirms safety to proceed.  
 
Step 2. Informed consent is given. 
 
Step 3. Computer generated code supplied and participant allocated to either sham 
or anodal tDCS.  
 
Step 4. UPPS-P Questionnaire completed by participant (5-10 minutes). 
 
Step 5. tDCS equipment shown to participant and attached. Example stimulation 
given to the participant (10- 20 seconds) 
 
Step 6. MEG scanner briefing 
 
Step 7. 3 x Anti-saccade tasks completed in the MEG (20 minutes each) while 
participant is delivered either anodal or sham tDCS. 
 
Step 8. Anatomical MRI acquisition.15 minute scanning session on either the 3 or 7 
tesla MRI systems.  
 
Step 9. Participant asked to guess the randomisation procedure, and response noted. 
Participant thanked, post-tDCS questionnaire completed, participant debriefed and 
paid £40.  
 
Compliance 
N/A as this is a one-off study.  
 
Criteria for terminating the study 
It is unlikely the study will be terminated. However, should this occur, it is likely to do with 
pragmatic reasons due to tight 12-month funding (study finishing end of February 2019). 
 
Stopping whole study: 
 
Funders decide to terminate the study early.  
 
Long-term difficulties with the facility (unforeseen circumstances). For example, if the 
MEG scanner is not working.  
 
tDCS and imaging safety:  
The tDCS safe procedure is considered to be low risk. Current evidence from extensive work 
shows there are no major side effects apart from skin irritation at the site of stimulation and 
headache. In principle, tDCS might induce seizures but this has never been reported in the 
literature (Poreisz et al., 2007). If during the course of the study any evidence emerges of 
significant risk then we will stop the study.  
 
Similarly, at present there is low risk for taking part in MRI or MEG studies, but should 
significant safety concerns arise during the course of the study, the study will be terminated.  
 
Stopping single participant:  

 
 
 
Page 14 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
A single participant testing session may be terminated if:  
 
The participant requests to leave the study 
 
The participant is experiencing significant adverse effects from the study (e.g., a 
headache). 
 
ANALYSES 
 
Methods  
All members of the study team will be involved in the evaluation, analysis and write up of 
findings.  
 
Analysis of beta and alpha band MEG data will follow analysis cited by Hwang et al (2014). 
Between subjects’ differences in the effects of tDCS on task performance will be examined 
using the Reaction Time and failure to saccade before and after stimulation. Independent 
samples t-test will be used for normally distributed data. Otherwise, the Mann-Whitney 
tests will be used. Correlational analysis will be used to examine the relationship between 
scores on UPPS-P, anti-saccade task performance and oscillatory activity over ROI. 
 
SPSS (version 24) will be used for analysis as well as in-house Matlab protocols. Analysis 
will take place on UoN computers and backed up to the UoN servers.  
 
Sample size and justification 
A sample size of 60 was estimated. This is based on a power calculation using an 
independent-sample t-test (G*Power; Faul et al., 2007). This yielded a total sample size of 
60 participants, with an effect size of d = 0.65, 80% power and alpha error probability of α 
= 0.05 (one tailed testing). 
 
ADVERSE EVENTS 
It is unlikely that adverse events will occur as a result of participation in the study. However, 
as the study involves stimulation of the brain, a management plan for adverse events will be 
briefly described here.  
 
Participants will be provided with written information on the debriefing sheet with contact 
details (mobile phone number) for Dr Najat Khalifa (CI and Consultant Forensic Psychiatrist) 
should they experience any adverse events (e.g., headache). Dr Khalifa will speak to the 
participant to understand the nature of the concern or complaint, and either provide 
reassurance or, if appropriate, recommend the person goes to see their GP.  
 
Any adverse events data will be collected and stored during the course of the study.  
 
ETHICAL AND REGULATORY ASPECTS 
 
It is not anticipated any sensitive or personal information will be disclosed as a result of a 
person’s participation in the study. The only anticipated ethical issue is outlined here. 
 
Patient safety 
 
Participants will be selected carefully using the tDCS safety questionnaire such that those with a 
history of epilepsy, brain injury or other neurological conditions or those who have metal implants 
(contraindications to the use of tDCS) will be excluded (this is also clearly stated in study 
advertising).  

 
 
 
Page 15 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
A dual safety check will be conducted with an initial safety screening for tDCS and imaging 
conducted over the telephone prior to booking, and an additional check on the day of the 
appointment. All researchers conducting such screening are familiar with, and trained in, the 
safety of participants using tDCS and brain imaging.   
 
In addition to this, a separate tDCS Information Sheet (attached) will be given to participants with 
the standard Participant Information Sheet so they are aware of potential side effects. 
Additionally, a tDCS side effect questionnaire will be completed for each participant at the end of 
the tDCS session, and each participant will be debriefed. As described above, should adverse 
effects occur after the study has been completed, participants can contact Dr Najat Khalifa 
directly to discuss the issue with him directly. It is likely to be suggested the participant make an 
appointment to see their GP.  
 
The duration of the study is 4-hours and participants may become fatigued. They will be informed 
they can take a break when they want to.  
 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
The study will not be initiated before the protocol, consent forms and participant information 
sheets have received approval / favourable opinion from the Research Ethics Committee 
(REC), the respective National Health Service (NHS) or other healthcare provider’s Research 
& Development (R&D) department, and the Health Research Authority (HRA) if required. 
Should a protocol amendment be made that requires REC approval, the changes in the 
protocol will not be instituted until the amendment and revised informed consent forms and 
participant information sheets (if appropriate) have been reviewed and received approval / 
favourable opinion from the REC and R&D departments. A protocol amendment intended to 
eliminate an apparent immediate hazard to participants may be implemented immediately 
providing that the REC are notified as soon as possible and an approval is requested. Minor 
protocol amendments only for logistical or administrative changes may be implemented 
immediately; and the REC will be informed. 
 
The study will be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, 1996; the principles of Good Clinical Practice, and the 
Department of Health Research Governance Framework for Health and Social care, 2005. 
 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
The process for obtaining participant informed consent will be in accordance with the REC 
guidance, and Good Clinical Practice (GCP) and any other regulatory requirements that 
might be introduced. The investigator and the participant shall both sign and date the 
Consent Form before the person can participate in the study. 
 
The participant will receive a copy of the signed and dated forms and the original will be 
retained in the Study records.  
 
The decision regarding participation in the study is entirely voluntary. The investigator or their 
nominee shall emphasize to them that consent regarding study participation may be 
withdrawn at any time without penalty or affecting the quality or quantity of their future 
medical care, or loss of benefits to which the participant is otherwise entitled. No study-
specific interventions will be done before informed consent has been obtained. 
 

 
 
 
Page 16 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
The investigator will inform the participant of any relevant information that becomes available 
during the course of the study, and will discuss with them, whether they wish to continue with 
the study. If applicable they will be asked to sign revised consent forms. 
 
If the Consent Form is amended during the study, the investigator shall follow all applicable 
regulatory requirements pertaining to approval of the amended Consent Form by the REC 
and use of the amended form (including for ongoing participants). 
 
For Questionnaires: 
Completion and subsequent return of questionnaires will occur during the study session and 
therefore separate written informed consent will not be sought. 
 
RECORDS  
Case Report Forms  
Each participant will be assigned a study identity code number, for use on CRFs, other study 
documents and the electronic database.  
 
CRFs will be treated as confidential documents and held securely in accordance with 
regulations. The investigator will make a separate confidential record of the participant’s 
name, date of birth, Participant Study Number, to permit identification of all participants 
enrolled in the study, in case additional follow-up is required. 
 
CRFs shall be restricted to those personnel approved by the Chief or local Investigator and 
recorded as such in the study records. 
 
All paper forms shall be filled in using black ballpoint pen. Errors shall be lined out but not 
obliterated by using correction fluid and the correction inserted, initialled and dated. 
The Chief or local Investigator shall sign a declaration ensuring accuracy of data recorded in 
the CRF. 
 
Source documents  
Source documents shall be filed at the investigator’s site and may include but are not limited 
to, consent forms, study records, field notes, interview transcriptions and audio records. A 
CRF may also completely serve as its own source data. Only study staff shall have access to 
study documentation other than the regulatory requirements listed below. 
 
Direct access to source data / documents 
The CRF and all source documents shall made be available at all times for review by the 
Chief Investigator, Sponsor’s designee and inspection by relevant regulatory authorities.  
 
DATA PROTECTION  
All study staff and investigators will endeavour to protect the rights of the study’s participants 
to privacy and informed consent, and will adhere to the Data Protection Act, 1998. The CRF 
will only collect the minimum required information for the purposes of the study. CRFs will be 
held securely, in a locked room, or locked cupboard or cabinet. Access to the information will 
be limited to the study staff and investigators and any relevant regulatory authorities (see 
above). Computer held data including the study database will be held securely and password 

 
 
 
Page 17 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
protected. All data will be stored on a secure dedicated web server. Access will be restricted 
by user identifiers and passwords (encrypted using a one way encryption method). 
 
Information about the study in the participant’s record will be treated confidentially in the 
same way as all other confidential medical information. 
 
Electronic data will be backed up every 24 hours to both local and remote media in encrypted 
format. 
 
 
QUALITY ASSURANCE & AUDIT  
 
INSURANCE AND INDEMNITY 
Insurance and indemnity for clinical study participants and study staff is covered within the 
NHS Indemnity Arrangements for clinical negligence claims in the NHS, issued under cover 
of HSG (96)48. There are no special compensation arrangements, but study participants 
may have recourse through the NHS complaints procedures. 
 
The University of Nottingham as research Sponsor indemnifies its staff, research 
participants and research protocols with both public liability insurance and clinical trials 
insurance. These policies include provision for indemnity in the event of a successful 
litigious claim for proven non-negligent harm.  
 
STUDY CONDUCT 
Study conduct may be subject to systems audit for inclusion of essential documents; 
permissions to conduct the study; CVs of study staff and training received; local document 
control procedures; consent procedures and recruitment logs; adherence to procedures 
defined in the protocol (e.g. inclusion / exclusion criteria,  timeliness of visits); accountability 
of study materials and equipment calibration logs. 
 
STUDY DATA  
Monitoring of study data shall include confirmation of informed consent; source data 
verification; data storage and data transfer procedures; local quality control checks and 
procedures, back-up and disaster recovery of any local databases and validation of data 
manipulation.  
 
Entries on CRFs will be verified by inspection against the source data. A sample of CRFs 
(10% or as per the study risk assessment) will be checked on a regular basis for verification 
of all entries made. In addition the subsequent capture of the data on the study database will 
be checked. Where corrections are required these will carry a full audit trail and justification. 
 
Study data and evidence of monitoring and systems audits will be made available for 
inspection by the REC as required. 
 
RECORD RETENTION AND ARCHIVING 
In compliance with the ICH/GCP guidelines, regulations and in accordance with the 
University of Nottingham Code of Research Conduct and Research Ethics, the Chief or local 
Principal Investigator will maintain all records and documents regarding the conduct of the 
study. These will be retained for at least 7 years or for longer if required. If the responsible 

 
 
 
Page 18 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
investigator is no longer able to maintain the study records, a second person will be 
nominated to take over this responsibility.  
 
The study documents held by the Chief Investigator on behalf of the Sponsor shall be finally 
archived at secure archive facilities at the University of Nottingham.  This archive shall 
include all anonymised audio recordings, study databases and associated meta-data 
encryption codes. 
 
DISCONTINUATION OF THE STUDY BY THE SPONSOR  
The Sponsor reserves the right to discontinue this study at any time for failure to meet 
expected enrolment goals, for safety or any other administrative reasons.  The Sponsor shall 
take advice as appropriate in making this decision. 
 
STATEMENT OF CONFIDENTIALITY  
Individual participant medical or personal information obtained as a result of this study are 
considered confidential and disclosure to third parties is prohibited with the exceptions noted 
above. 
 
Participant confidentiality will be further ensured by utilising identification code numbers to 
correspond to treatment data in the computer files. 
 
Such medical information may be given to the participant’s medical team and all appropriate 
medical personnel responsible for the participant’s welfare.  
 
If information is disclosed during the study that could pose a risk of harm to the participant or 
others, the researcher will discuss this with the CI and where appropriate report accordingly. 
 
Data generated as a result of this study will be available for inspection on request by the 
participating physicians, the University of Nottingham representatives, the REC, local R&D 
Departments and the regulatory authorities. 
 
 
PUBLICATION AND DISSEMINATION POLICY 
 
We intend to publish findings in peer-reviewed journals, and present findings at academic 
conferences. Participants will not be identified in any publications.  
 
USER AND PUBLIC INVOLVEMENT 
 
Prior to the main study, a brief pilot study (up to 5 participants) will be conducted to test the 
protocol. Participants will spend up to 1 hour in MEG for the purpose of optimising 
performance of the MEG system during concurrent tDCS and MEG. 
 
Participants will not be involved in the dissemination of the study.  
 
STUDY FINANCES 
 
Funding source  
This study is funded by Medical Research Council (Nottingham Confidence in Concept 
Award, School of Medicine).  

 
 
 
Page 19 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
Participant stipends and payments 
Participants will be paid £40 for their participation in the study (Approximately £10 p/hour). 
Travel expenses will not be offered. 
 
SIGNATURE PAGES 
 
Signatories to Protocol: 
 
Chief Investigator: (name) Dr Najat Khalifa 
 
 
Signature:__________________________________ 
 
 
Date: 08.01.2018 
 
 
REFERENCES 
 
Brevet-Aeby, C., Brunelin, J., Iceta, S., Padovan, C., & Poulet, E. (2016). Prefrontal cortex 
and impulsivity: interest of non-invasive brain stimulation. Neuroscience & Biobehavioral 
Reviews, 71, 112-134.  
 
Castellanos-Ryan, N., & Séguin, J. R. (2015). Prefrontal and Anterior Cingulate Cortex 
Mechanisms of Impulsivity. Beauchaine, T. P. & Stephen P. Hinshaw, S. P. (editors). The 
Oxford Handbook of Externalizing Spectrum Disorders. Oxford University Press – New 
York. DOI: 10.1093/oxfordhb/9780199324675.013.13 
 
Faul, F., Erdfelder, E., Lang, A. G., & Buchner, A. (2007). G* Power 3: A flexible statistical 
power analysis program for the social, behavioral, and biomedical sciences. Behavior 
Research Methods, 39(2), 175-191. 
 
Hanley, C. J., Singh, K. D., & McGonigle, D. J. (2016).  Transcranial modulation of brain 
oscillatory responses: A concurrent tDCS–MEG investigation. NeuroImage, 140, 20–32. 
 
Hwang, K., Ghuman, A. S., Manoach, D. S., Jones, S. R., & Beatriz Luna, L. (2014). Cortical 
Neurodynamics of Inhibitory Control. The Journal of Neuroscience, 34(29):9551–9561. 
 
Lynam, D. R., Smith, G. T., Whiteside, S. P., & Cyders, M. A. (2006). The UPPS-P: 
Assessing five personality pathways to impulsive behavior. West Lafayette, IN: Purdue 
University. 
 
Poreisz C, Boros K, Antal A, Paulus W: Safety aspects of tDCS concerning healthy subjects 
and patients. Brain Res Bull 2007, 72: 208-214. 
 
Self, D. R., De Vries Henry, E., Findley, C. S., & Reilly, E. (2006). Thrill seeking: the type T 
personality and extreme sports. International Journal of Sport Management and 
Marketing, 2(1-2), 175-190. 
 
Self, D. R., De Vries Henry, E., Findley, C. S., & Reilly, E. (2006). Thrill seeking: the type T 

 
 
 
Page 20 of 20 
 
tDCS and Inhibitory Control. Study Protocol V1. 08.01.2018 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
personality and extreme sports. International Journal of Sport Management and 
Marketing, 2(1-2), 175-190.