standard operating procedure imagen follow-up 3 study

Standard Operating Procedure IMAGEN Follow-up 3 study

August 2016

INSTITUTE ASSESSMENT Overview ......................................................................................................................................... 3

1.1 Welcome Session ............................................................................................................ 4

1.2 Checking home assessment completion/reliability .......................................................... 5

1.3 Sensitive Interviews ......................................................................................................... 51.3.1 What if there are obvious signs of distress? ............................................................ 5

1.4 Feedback Session ........................................................................................................... 6

2 Neuroimaging ......................................................................................................................... 7

2.1 MRI Pre-Screening and Institute Screening .................................................................... 7

2.2 Neuroimaging data collection .......................................................................................... 8

2.2.1 Overview of Imaging Session: ................................................................................. 8

2.2.2 Functional Tasks: .................................................................................................... 92.2.3 fMRI Software Installation ........................................................................................ 9

2.2.4 Installation of fMRI tasks ....................................................................................... 10

2.2.5 Run tasks ............................................................................................................... 10

2.2.6 Start window of the fMRI battery ........................................................................... 11

2.2.7 Scanning session window of the fMRI battery ....................................................... 11

2.2.8 Practice session and Post-Scanning session ........................................................ 13

2.2.9 Time flow of the scanning session ......................................................................... 14

2.3 Neuroimaging (and related data) transfer ...................................................................... 152.3.1 Hardware ............................................................................................................... 15

2.3.2 Transferring the DICOM files to the router: ........................................................... 15

2.3.3 Logfiles .................................................................................................................. 16

2.3.4 Data Transfer Procedure ....................................................................................... 17

2.3.5 Neuroimaging Quality Control ............................................................................... 18

3 Cambridge Neuropsychological Test Automated Battery (CANTAB) ................................... 19

3.1 Data Acquisition ............................................................................................................. 19

3.2 Overview of Task Battery .............................................................................................. 193.3 Test Instructions ............................................................................................................ 19

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3.3.1 CANTAB Spatial working memory ......................................................................... 20

3.3.2 CANTAB Cambridge Guessing Task (modified) ................................................... 21

3.3.3 CANTAB Intra-Extra Dimensional Set Shift ........................................................... 22

3.4 CANTAB Outcome measures ........................................................................................ 223.5 Data Backup .................................................................................................................. 27

4 Psytools Institute Assessments ............................................................................................ 28

4.1 Passive Avoidance Learning Paradigm (PALP) ............................................................ 28

4.1.1 Overview ................................................................................................................ 28

4.1.2 Introduction ............................................................................................................ 29

4.1.3 Main Test ............................................................................................................... 29

4.1.4 Trial Timeline ......................................................................................................... 29

4.2 SRC ............................................................................................................................... 305 Time-Line-Follow-Back ......................................................................................................... 31

6 Biological Sample Collection and Storage ............................................................................ 32

7 Mini-International Neuropsychiatric Interview (MINI) ............................................................ 32

7.1 Overview of the MINI modules: ..................................................................................... 32

7.2 General Instructions ...................................................................................................... 32

7.3 Conventions ................................................................................................................... 33

7.4 Rating instructions: ........................................................................................................ 33

8 Wechlser Adult Intelligence Scale (WAIS) ............................................................................ 349 APPENDIX ............................................................................................................................ 36

9.1 Neuroimaging ................................................................................................................ 36

9.2 CANTAB ........................................................................................................................ 42

9.3 Passive Avoidance Learning Paradigm (PALP) ............................................................ 54

9.4 Timeline Follow Back (TLFB) ........................................................................................ 56

9.4.1 Administration Script .............................................................................................. 57

9.4.2 Example Prompts/Questions ................................................................................. 609.4.3 Local Help per Site/Country ................................................................................... 62

9.4.4 Example Calendar ................................................................................................. 63

9.4.5 Scoring the TLFB ................................................................................................... 65

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Overview

A case report form (CRF) should be prepared for each participant. The files are organised by

CRF and contain personal details as well as pseudocodes so these files have to be handled with

special care. Please maintain confidentiality and secure storage. A template of the CRF for FU3

in English will be made available on Milliarium.

Gap between HA and IA: should be kept as short as possible (~2 weeks); although we appreciate

it is not always possible to book your participants for some time after they have completed the

HA. Therefore, recommend that you do not send the DI for the HA until you know when your

person will be due in. If the gap is large please repeat the HA in advance of the IA; possibly offer

your participant additional compensation to do this. Not all will agree. Where they do not agree

please write this in the Recruitment information file so we know how long they have between the

IA and HA.

Consent: should a participant take part and complete some of the tasks but declines further

participation, their data may be used unless they have indicated that they want their data

destroyed.

Recruitment information file should be compiled each month by each site and sent to the Follow -

Up 3 Recruitment Co-ordinator (Erin Quinlan) at the end of every month. The recruitment file

should list participants by their Pseudo-code and details what parts of recruitment, home

assessment and institute assessment have been completed for each participant. A template file

will be circulated by the recruitment co-ordinator. In addition each site will have to keep an excel

file documenting the dates each participant completed each assessment (i.e. Psytools, DAWBA,

CANTAB, Imaging, Blood and Hair collection). This is important, as it will help prevent confusion

about what was done when and is particularly relevant for easier database maintenance. A

template of this file will be uploaded on Milliarium.

If the participant has not yet completed their Home Assessment before the Institute Assessment

then the participant should complete the AUDIT & ESPAD questionnaires from Psytools, at the

very least, during their Institute Assessment. If feasible the participant can then complete the rest

of their Home Assessment during the Institute Assessment, with emphasis on the substance use

and psychopathology measures. However, we urge you to send reminders to the participants to

complete the HA before the IA.

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1.1 Welcome Session

The following text is designed to make your participant feel at home at the research centre, and

although there are points we insist you cover (see bullet points below), the welcome sessions

may vary site-by-site.

• The participants are welcome to take breaks as and when they require

• Emphasise voluntary nature of the study (withdrawal is allowed without giving reason)

• Emphasise confidentiality and anonymity

• Give participants time to ask you questions about the day and about any of our

procedures

• Please conduct welcome session and de-brief in a confidential environment

• Please remember to have your home assessment checks complete so you can include

task repetition if necessary as part of your assessment day

An example welcome session is detailed below:

“Good morning/afternoon, I’m [researcher name], thank you very much for agreeing to come

along today we’re very grateful you decided to take part again. How was your journey here? [at

this point you can refund travel costs if you need to – get the receipt!]. Can I get you something

to drink? So we’ll get started in just a few minutes, there are quite a few things we’ll be doing

today. You’ll start out by doing some computer based tasks and an interview, then I’ll take you to

another building to have your MRI scan, and we’ll end the day with the blood test and hair

collection. You should be finished by around (insert time). Everything we are asking you to do

today is completely voluntary, so if you feel you’re unable to continue with any of the tasks and

need to stop, then you are able to do so without offering us any explanation. Of course we really

appreciate it if you feel you can do everything! All of the information you give us are kept strictly

confidential and are anonymised. We are unable to check your answers, all we’re able to check is

if you have completed the task or not. So if you have completed one of the questionnaires in a

certain way, because you were hoping that we’d notice that something was bothering you, I’m

afraid we’ve just got no way of checking. If there is something that’s bothering you then you’re

really very welcome to let us know. Do you have any questions about today? Just let me know if

you need anything and if you need to take a break.”

IMAGEN is a non–intervention study so we are limited in the level of support we can provide. The

important thing is to let your participant know that while we are not able to check their answers we

are able to recommend local services that can help them if they feel they need to speak to a

professional about a problem. Do have your helplines available in the event that your participant

wants to discuss something that is bothering them.

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1.2 Checking home assessment completion/reliability

If any of the Home Assessment tasks have been completed with dubious reliability you can use

the welcome session as a chance to check through the tasks. This gives you a chance to thank

your participant for taking the time to complete the tasks and also gives you the opportunity to

schedule additional time to re-complete the tasks if necessary. Please note that if the Home

Assessment has not been completed previously to the Institute Assessment, please make sure to

schedule extra two and a half hours for DAWBA and Psytools completion.

An example script is below:

“I can see from your Home Assessment that you have completed this in advance of your visit,

thank you very much, we really are very grateful you took the time out of your day to do this. I see

that for the assessment about your personality, it was called Personality II that you indicated you

were in a rush. Do you recall what made you report that you were rushing that day? Do you think

your answers were truly rushed?”

1.3 Sensitive Interviews

Please ensure that the welcome session explicitly mentions the anonymity and confidentiality of

the answers the participant gives. It’s imperative this is made clear as the participant could enter

sensitive information hoping for somebody from the research team to read it and take action.

1.3.1 What if there are obvious signs of distress?

Please act sensibly and do not sensationalise the situation. It is important to be calm and

empathic, we have composed some suitable text to deal with this situation should it arise.

Researcher: “Are you alright? If that has bought up some difficult memories why don’t

we take a time out? Please don’t feel as though you must continue. Can I make you a

drink?”

Researcher: “We do have the details of some support services here in

England/Ireland/Germany/France; may I pass them over to you? We issue these to all

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the participants who take part in the study, but they exist in case people feel as though

they need to take some time out to speak to someone”.

Researcher: “In terms of re-starting the session, would you like to leave things here for

today and take a break? It is your choice whether you want to continue or not”.

It is important that no one overreacts, your job as a good researcher is to make the participant

feels comfortable and show that it’s ok to talk about things that are upsetting, with the appropriate

organisation. Please do not automatically assume that the person will want to stop the interview

and try not to make any assumptions about their situation.

If the situation is not manageable, i.e. the individual has explicitly asked you for help, please

inform them that you are not clinically trained [depending on training level], but that you are able

to speak with a more senior member of staff to help them if they feel they need to speak with

somebody. We hope this does not become the case at any site; however these situations can

happen. Please ensure you have a clinically trained member of staff that you are able to contact

in the circumstance where the participant cannot be suitably comforted by the researcher.

1.4 Feedback Session This session is important; it gives you the opportunity to fully thank your participant for taking part

in the study. Please do make a fuss over them, it’s important they know just how grateful we are,

we would not have a study sample had they not given up their time so please tell them as such.

Please check again all the tasks have been completed with good reliability, or if the reliability is

not good that a suitable explanation has been recorded.

o Is the Home Assessment complete?

o Have tasks that needed to be repeated been repeated?

As a ‘thank you’ we are issuing the participants with compensation for their time, please ensure

this is given to each participant as per your local ethical approval. By now you should have issued

the participant with the contact details of mental health organisations in your country, please

check this has been done. Enquire what they felt was their favourite part of the day, ask them

also if there is anything they think we should do better. It’s good to get their feedback. Check that

any travel expenses have been reimbursed. Finally thank the participant again and ensure they

are able to find their way from the study centre.

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2 Neuroimaging

Important: Both nicotine and caffeine affect BOLD signal but simple abstinence only works well

with light users. Therefore, the participants who are light nicotine and/or caffeine users

should be instructed to be caffeine and nicotine free for 24 hours before the Institute Assessment. Where possible, only give decaffeinated beverages to participants while they are

being assessed and request that users of nicotine refrain from smoking during the assessment.

For heavy users (more than 5 cups of coffee a day and daily smokers), the abstinence

period should be 4 hours before the scan.

2.1 MRI Pre-Screening and Institute Screening

A short questionnaire will be sent to the participant regarding MRI contraindications that may

result in exclusion from the scanning part of the study. This questionnaire should be sent in the IC

pack, stapled together with the participant consent form. Any queries should be discussed

between the researcher and the participant over the phone. Please note participants who have braces should not be scanned until the braces are removed. Braces can cause extensive

signal loss so it is preferable to wait until they are removed.

A complete screening for MRI exclusion criteria will also be administered to every participant on

the day of the MRI scan. The questions consider pregnancy for females and also non-removable

piercings and tattoos. Please provide confidential surroundings when performing further MRI

screening checks.

As a standard procedure, every female participant is routinely screened for potential pregnancy

on the day of scanning to avoid damage to the unborn child. In case actual pregnancy is revealed

the participant will be excluded from the neuroimaging session. In case a pregnancy may be

present but is doubtful, a urine-based pregnancy test will be offered in confidential surroundings.

If the participant does not want to administer the test or the test is positive, the participant will be

excluded from the study.

In addition to the MRI exclusion criteria, (1) height and weight of the participant should be

measured to index BMI and (2) for the female participants the date of the last period and whether

they take hormonal contraceptives should be recorded. This data should be entered in Psytools

Institute login, under NI data.

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2.2 Neuroimaging data collection

2.2.1 Overview of Imaging Session:

Structural & Functional sequences Duration

1. Volunteers preparation / equipment adjustments 10:00 – 15:00

2. 3 plane localizer / Parallel imaging calibration 00:22

3. Axial T2 slices (site specific duration) ~01:19

4. Axial T2 Flair slices (site specific duration) ~02:25

5. 3D Sagittal ADNI MPRAGE (Long) 09:17

6. Instructions / talk to volunteer 0:40

7. Monetary Incentive Delay Task (MID) 07:07


9. Face task (FT) 07:30


11. Stop-signal task (SST) 12:50 (max) -

variable length

12. B0 Map 00:40

13. DTI (duration is heart-rate dependent at sites with cardiac gating) 10:00

14. Resting State 06:00

15. NODDI ~20-30 minutes

TOTAL (scanner time) TBD

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2.2.2 Functional Tasks:

MID (Monetary Incentive Delay) Task

This task is a reaction time task - it tests how quickly the subject can react and pull the trigger to

hit a target (with left or right index finger) that only appears for a short time on the left or right of

the screen. If the subject can hit the target, they will score points. The subject can tell where the

target will appear and how many points they can win by the symbol they see on the screen before

each trial. A triangle means no points, a circle with a line means 2 points and a circle with three

lines means 10 points. Responding too early or too late will result in a loss. The task lasts 7

minutes. The subjects will exchange their points for money (cash or vouchers) at the end to

increase their motivation. Every participant, independent of their performance, will receive £/€ 5

however, they must not be told this! They should believe that the final gain is related to their

performance!

Face task

In this task volunteers are asked to passively watch video clips presenting faces with neural,

happy and angry expressions as well as control non-biological motion stimuli (concentric circles).

After scanning a short recognition test is performed outside the scanner with 5 static pictures

extracted from the movies. The pictures are presented sequentially, each with the question:

"Have you seen this object while you were in the scanner?” The volunteers are NOT informed

that a recognition test will be performed after scanning.

Stop-signal Task

The main principle of this task is to respond to regular presented visual go stimuli (go trials) but to

withhold the motor response to the go stimulus when it is followed unpredictably by a stop-signal

(stop trials). This task yields an estimate of a subject's stop-signal reaction time (SSRT).

2.2.3 fMRI Software Installation

Installation of Microsoft .NET Framework Version 2.0

Task presentation and recording of the behavioural responses is performed using Visual Basic

2005 with .NET Framework Version 2.0. To run the tasks Microsoft .NET Framework Version 2.0

Redistributable Package (x86) has be installed first. The Microsoft .NET Framework version 2.0

(x86) redistributable package installs the .NET Framework runtime and associated files required

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to run applications developed to target the .NET Framework v2.0. For more information please

refer to the Microsoft homepage:

http://www.microsoft.com/downloads/details.aspx?familyid=0856EACB-4362-4B0D-

8EDDAAB15C5E04F5&displaylang=en

• To install Microsoft .NET Framework Version 2.0 Redistributable Package (x86) double-

click on the .NET Framework executable file (.exe)

• Follow the download and installation instructions

Contact: If problems occur during installation please contact Sanja Abbott, ([email protected])

from the Behavioural and Clinical Neuroscience Institute in Cambridge.

No changes to the parameters of functional tasks have been made for FU3. The only addition is

NODDI (for London, Dublin, Nottingham, Mannheim (Dresden)?); the parameters will be made

available at the end of August/early September. All files necessary to install the FU3 fMRI battery

are available on the Millarium homepage (https://www.milliarium.gabo.de/): IMAGEN/Follow-up 2

Study/fmri Battery/Battery2012.

2.2.4 Installation of fMRI tasks o Download all files to your local computer and unzip the files (e.g. using winscp). The

zipped folder “ImagenBattery2012” is available on Milliarium.

o Open the folder and double-click on ImagenBatterySetup2012.msi. A Setup Wizard

opens which guides you through the steps required to install the Imagenbattery on your

computer:

o Click next. Then choose your preferred installation folder C:\ProgramFiles\ImagenBattery

is recommended.

o Click next

o Confirm the installation of the IMAGEN battery on your computer by clicking next again.

o After installation is completed click close to exit the Setup Wizard.

o There is no need to restart your computer after the installation.

2.2.5 Run tasks Before running the tasks please make sure the screen resolution is set to 600 x 800.To start the

fMRI battery:

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o Open the folder C:\Program Files\ImagenBattery2012 (or the folder where you have

installed the fMRI battery).

o Start the fMRI battery by double clicking on the file Imagenbattery2012.exe

The start window opens.

2.2.6 Start window of the fMRI battery An example of the English version of the start window is presented in Figure 1.

o Enter ID: Please enter <PSC1>FU3 in the Patient DICOM field at scanning time, using

the barcode scanner to avoid human errors when entering the code. For FU3, the

barcodes will be read by the scanner as: <PSC1>FU3

o Please ensure that you use a barcode scanner (if it is available) to scan in the Patient’s

ID. If a barcode scanner is not available, it is pertinent to ensure that the ID is carefully

entered as <PSC1>FU3 (eg. 010001234567FU3). The ID should be the 12-digit PSC1

code followed by FU3 (in capital letters only). No other format will be accepted.

o Chose language of the fMRI battery (English, French or German)

o Chose what mode you want to use (practice, scanning etc.)

o Click ”Select” to confirm your selection and “Exit” to close the program

2.2.7 Scanning session window of the fMRI battery An example of the English version of the scanning window is presented in Figure 2.

o Click on the session. Choose which tasks you want to run. Please note the order is

predefined. If you tick the boxes of the 3 tasks they will be presented in that order.

o Test NNL grips: Press ‘Test NNL Response Grip’ to check whether the response grips

are working. Press each button of the grips separately and check whether the display

colours change. If so the response are registered correctly.

o This test has to be performed on the stimulus presentation computer on which the tasks

run during fMRI. In case you get no reply make sure the response grips are properly

attached to the computer.

o Test and adjust NNl goggles: Press ‘Test NNL Visual System’ -> A test picture is

presented which you can use to adjust the goggles

o If it is the scanner session always chose scanner sync (the start of the task is

synchronized with the scanner pulse). This is already the default option.

o Click ‘Run’ to start the first task

o A black screen appears and the initial letter of the task which will be presented next

appears in the upper right corner;

o Press enter to start the instructions of the respective task

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o If you press enter again a black screen appears with the word “ready” in the upper right

corner. Now the program is ready and waits for the scanner pulse to start the

presentation.

o After each task the following sentence is presented for 5 sec on the screen: ‘short break -

please relax’. Afterwards a black screen is presented and again the initial letter of the

following task appears in the upper right corner; the researcher can start the task by

pressing ‘enter’

o After all tasks have been presented the following sentence appear on the screen: ‘well

done - please wait’

Figure 1. Start Window of the fMRI battery.

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Figure 2. Scanning session window of the fMRI battery.

2.2.8 Practice session and Post-Scanning session All tasks need to be practiced outside the scanner on a computer on which the fMRI task battery

is installed. For the practice session, the left and right arrows on the computer keyboard are used

for tasks that involve button presses. Instruct the volunteer to place their left index finger on the

‘left arrow’ and their right index finger on the ‘right arrow’ of the computer keyboard. Start the

practice version of the task and give the instruction summarized under section 8.1 to the

volunteers. The scans must be administered in the following order:

o MID: Volunteers are familiarized with the task by performing a practice session block

outside the scanner. The practice session should last ~3 minutes.

o Face Task: Please present the task instructions outside the scanner. No practice trials

are performed for this task.

o SST: Volunteers are familiarized with the task by performing a practice session block of

60 trials outside the scanner. The practice session lasts ~ 2 minutes.

Postscanning session:

After the scanning session a recognition test is performed as part of the Face task. Place the

volunteer in front of the computer and start the recognition test (choose “Postscanning” and then

Face task: Recognition Test). The volunteer is asked which of the presented faces he has seen

during the scanning session.

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Please note: The results of this post scanning task need to be saved as a logfile on a memory

stick and uploaded to the local data computer for export.

2.2.9 Time flow of the scanning session 1. Switch on the NNL Sync Box and the Response-Grip optic-electric adapter.

2. Change the screen resolution of your primary monitor to 600x800.

3. Start fMRI battery by double-clicking on the IMAGENbattery.exe file again in the folder

4. C:\Program Files\ImagenBattery2012

5. Please enter <PSC1>FU3 in the Patient DICOM field at scanning time, using the barcode

scanner to avoid human errors when entering the code. For FU3, the barcodes will be

read by the scanner as: <PSC1>FU3

6. Chose scanning under scanning session and press select.

7. Click on the session A and the tasks you would like to run by ticking the boxes next to

them.

8. The next screen opens. Click on the button “NNL Response Grip” to test the response

device. Please press all buttons, one after the other, to check whether the display colour

changes.

9. Select “Test NNL visual system”. A test picture is displayed and the goggles can be

adjusted.

10. Position subject in scanner with:

a. Earplugs, NNL

b. Functional equipment (goggles and handsets): Adjust goggles for the volunteer

(use again the test picture) and let them press the buttons of the response grips

and check again whether they are working

c. Place pillow under subject’s knees

d. Provide blanket if needed

11. Make sure scanner sync is ticket (default) and double-check that you have selected the

correct session. Make sure you have selected all tasks of that session and click run.

Then black screen appears with the initial letter of the task chosen presented at the upper

right corner of the screen.

12. Tell the Radiographer which task/series to download

a. Session A. 1. MID Task / 2. Face task / 3. Stop-signal task

b. DO NOT DEVIATE FROM THIS ORDER

13. Talk to the volunteer:

a. Ask the volunteer whether he is ok and ready to start with the first scans.

b. Remind the subject to lie as still as possible

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c. Remind the volunteer that she or he can always press the alarm button if she or

he feels very uncomfortable and feels the urgent need of immediately being

removed out of the scanner. Note, that the interviewer talks to the volunteer

between the tasks.

d. If the volunteer affirms the inform the subject that scanning starts and that there

will be some scanner noise (3 to 4 minutes) and that he/she will talk again to the

volunteer after these scans

14. Radiographer starts the first structural scans (see overview MR sequences)

15. After the structural scans the researcher talks to the volunteer and ask him or her

whether he/she is ok. Then inform him/her which task is next.

16. Researcher informs subject that instructions are about to be shown and there will be

some scanner noise (from the prepscan), but to stay focused on the instructions

17. Researcher starts the instructions and Radiographer performs prepscan (data dummy

acquisition (DDAs))

18. Radiographer tells Researcher when prepscan is finished and ready to scan

19. Researcher checks that the subject is ready to start the task

20. Researcher hits “Return” on the task console keyboard (a black screen appears with the

word “ready” in the upper right corner)

21. Radiographer presses “Scan” on the scanner

*****Repeat steps 12 to 19 for all the tasks of this session*****

2.3 Neuroimaging (and related data) transfer

2.3.1 Hardware All Scito site servers are up and running. Scito has developed a “short-circuit LDC” on the router

which directly pushes data from the router to Neurospin including PSC1-verification and

anonymisation and includes the transfer of the CANTAB and fMRI behavioural data. All sites will

need to have a PC with access to the ‘nil’ (Z) drive set up that can be connected to the Scito

router. This PC must have a static, private IP address.

2.3.2 Transferring the DICOM files to the router: Image acquisition should follow exactly the same conventions as for the baseline. The subjects

follow up data have the **same PSC** as at baseline but with the additional suffix ‘FU3’. The

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name of the acquisitions should read EPI_MID_FU3, EPI_SST_FU3, EPI_Face_FU3, and

EPI_Rest_FU3.

Before pushing, check the images on the scanner console and transfer the data only if you think it

can be used. Please see the next section on how to enter notes about the imaging session. One

push for all series of a single exam is preferable.

2.3.3 Logfiles Please save the fMRI logfiles for each functional task. Please ensure you keep backups of these

files in the event you need to re-send data at any point.

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2.3.4 Data Transfer Procedure [Information compiled by Ruediger Bruehl, Vincent Frouin and Arno Klassen]

Once DICOM data have been transferred to the SCITO router a directory will appear, the

following information is used as an example from the Berlin site.

Z:\exported\040000090214FU3

This directory will contain:

• A sub directory called 'ImageData'; this is where one will see all Dicom files in a flat

directory, no editing is possible, though viewing is.

• A sub directory called 'AdditionalData' in which to copy data associated with the scanning

session; this directory already contains a file called 'QualityReport.csv'

• A file called 'DELETE_THIS_FILE_WHEN_Study_Complete'

Copy the fMRI logfiles: 'mid_<PSC1>FU3.csv', 'ft_<PSC1>FU3.csv', 'ss_<PSC1>FU3.csv' and

recog_<PSC1>FU3.csv and physiological recordings for the resting state to the

'Z:/exported/<PSC1>/AdditionalData' directory. Your directory should look similar to this one:

Z:\exported\040000090214FU3\AdditionalData\scanning\

\mid_040000090214FU3.csv

\ft_040000090214FU3.csv

\ss_040000090214FU3.csv

\recog_040000090214FU3.csv

\040000090214FU3.ecg

\040000090214FU3.resp

\040000090214FU3.puls

\040000090214FU3.ext

In the additional data file please copy your CANTAB logfiles. The folder should look like this:

Z:\exported\040000090214FU3\AdditionalData\

\cant_040000090214FU3.cclar

\datasheet_040000090214FU3

\detailed datasheet_040000090214FU3

\report_040000090214FU3

In the event you encountered any difficulties during the acquisition session please edit the file

'QualityReport.csv'. If there are no comments then all scan data are presumed to be good/reliable

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quality. Please try and keep your comments short. CANTAB reliability is entered in Psytools

under the Institute login.

When you are satisfied that all the data are present and have appropriate comments where

necessary you are ready to send the file. Please delete the file:

Z:\exported\<PSC1>\DELETE_THIS_FILE_WHEN_Study_Complete'

As soon as this file is deleted the router is programmed to automatically transfer the data to

Neurospin and the file will no longer be viewable to you. You have successfully transferred your

data! If you experience any difficulties with data transfer please contact the London team who will

put you in contact with the appropriate person at Neurospin.

Transfer of Behavioural Files when no imaging data has been acquired - TBC at a later date when all data is being transferred successfully through SCITO routers.

2.3.5 Neuroimaging Quality Control The ACR phantom should be scanned at least twice a year, and only three sequences are to be

applied:

• Localiser

• MPRAGE

• Resting State EPI (no physiological recording needed)

Acquisition parameters are the same as the in vivo measurements, please also make sure your

NNL goggles are in place and switched on. Scanning the dodecane phantom (a baseline

measure) is not necessary at this stage. This acquisition should only take around 20 minutes in

total.

Please acquire the scan under the phantom PSC used at baseline and contact Erin if you are

unsure what this code is.

Once the first phantom acquisition is performed please ensure phantom scans are taken every 6

months thereafter until your site has completed the study.

19

3 Cambridge Neuropsychological Test Automated Battery (CANTAB)

3.1 Data Acquisition

Please make sure when you run the CANTAB that you only ever run the IMAGEN Battery. Do not

deviate from this; the tasks have been modified for our use. We are going to be running the tests

with the same PSCs as baseline. The PSC will need to be entered with the FU3 suffix, e.g.

01000001234FU3.

3.2 Overview of Task Battery

Test Name Abbr. Dur.

CANTAB 1. Spatial Working Memory SWM 8 min

CANTAB 2. Cambridge Guessing (Gambling) Task [Ascending first; 2s

(modified: shorter interval between stakes)]

CGT 15 min

CANTAB 3. Intra-Extra Dimensional Set Shift IED 7 min

Total Duration 30 min

1. Spatial Working Memory

2. Cambridge Guessing (Gambling) Task

3. Intra-Extra Dimensional Set Shift

3.3 Test Instructions

CANTAB Test Administration Guide

A good overview of how to use the CANTAB Eclipse software is provided in the powerpoint

presentation CANTAB_Software_tour.ppt and CANTAB_product_overview.ppt in the folder

Cantab_Eclipse on the Milliarium homepage. Please refer to the relevant pages in the

CANTABeclipse Test Administration Guide accompanying the CANTAB System for a precise

20

description of how to administer the CANTAB tests (you should already have this). Please refer to

the CANTAB Test Administration Guide in the Appendix

Each site should have complete test instructions per language from baseline. Please refer to this

for actual task administration guidance.

3.3.1 CANTAB Spatial working memory

Overview

SWM is a test of the subject’s ability to retain spatial information and to manipulate remembered

items in working memory. It is a self-ordered task, which also assesses heuristic strategy. This

test is a sensitive measure of frontal lobe and ‘executive’ dysfunction.

Administration time

Around 8 minutes, depending on level of impairment

Task

The test begins with a number of coloured squares (boxes) being shown on the screen. The aim

of this test is that, by touching the boxes and using a process of elimination, the subject should

find one blue ‘token’ in each of a number of boxes and use them to fill up an empty column on the

right hand side of the screen. The number of boxes is gradually increased, until it is necessary to

search a total of eight boxes. The colour and position of the boxes used are changed from trial to

trial to discourage the use of stereotyped search strategies.

Test modes

Clinical mode.

Outcome measures The twenty-four outcome measures for SWM include errors (touching boxes that have been

found to be empty and revisiting boxes which have already been found to contain a token), a

measure of strategy, and latency measures.

21

3.3.2 CANTAB Cambridge Guessing Task (modified)

Please note that the test has been renamed for IMAGEN due to ethical concerns – please refer to

Cambridge Gambling Task in the manual)

Overview

The Cambridge Guessing Task was developed to assess decision-making and risk-taking

behaviour outside a learning context. Relevant information is presented to the subjects ‘upfront’

and there is no need to learn or retrieve information over consecutive trials.

Administration time

Up to 30 minutes; IMAGEN version 15-20 minutes

Task

On each trial, the subject is presented with a row of ten boxes across the top of the screen, some

of which are red and some of which are blue. At the bottom of the screen are rectangles

containing the words ‘Red’ and ‘Blue’. The subject must guess whether a yellow token is hidden

in a red box or a blue box. In the gambling stages, subjects start with a number of points,

displayed on the screen, and can select a proportion of these points, displayed in either rising or

falling order, in a second box on the screen, to gamble on their confidence in this judgement. A

stake box on the screen displays the current amount of the bet. The subject must try to

accumulate as many points as possible.

Test modes

Ascending first (where stakes are displayed in ascending order for two stages, then in

descending order for two stages) and Descending first (where stakes are displayed in descending

order for two stages, then in ascending order for two stages). For IMAGEN we will use a modified

version in which the time between stakes is reduced from 5s to 2s to make the task shorter and

more interesting for participants. The new version is called Cambridge Guessing Task:

ascending first-2s.

Outcome measures

The six CGT outcome measures cover risk taking, quality of decision-making, deliberation time,

risk adjustment, delay aversion and overall proportion bet.

22

3.3.3 CANTAB Intra-Extra Dimensional Set Shift Overview

IED is a test of rule acquisition and reversal. It features

• visual discrimination and attentional set formation

• maintenance, shifting and flexibility of attention

This test is primarily sensitive to changes to the frontal-striatal areas of the brain.

Administration time

Around 7 minutes.

Task

Two artificial dimensions are used in the test:

• colour filled shapes

• white lines

Simple stimuli are made up of just one of these dimensions, whereas compound stimuli are made

up of both, namely white lines overlying colour filled shapes.

Subjects progress through the test by satisfying a set criteria of learning at each stage (6

consecutive correct responses). If at any stage the subject fails to reach this criterion after 50

trials, the test terminates.

Test modes

The IED has one clinical mode, plus 7 parallel modes. The difference between these modes is

solely in the stimuli used, which are different shapes and lines. One administration script (given in

the manual) applies to all the different setups. We will use the clinical mode for FU3.

3.4 CANTAB Outcome measures

Spatial Working Memory

Test Measure Definition Sense Units Range

SWM Between errors (by

number of boxes,

4, 6 or 8)

Between errors are defined as times the subject

revisits a box in which a token has previously been

found. This is calculated for trials of four or more

tokens only.

-ve 0-360

SWM Strategy For problems with six boxes or more, the number of

distinct boxes used by the subject to begin a new

-ve 8-56

23

search for a token, within the same problem.

Cambridge Guessing (Gambling) Task

Test

Measure Definition Sense Units Range

CG

T

Quality of

decision

making

The proportion of occasions, during the initial phases of

each trial, on which the subject chose the majority box

colour. This is calculated across all assessment trials

on which the number of boxes in each colour differed.

+ve 0-1

CG

T

Deliberation

time

The mean latency from presentation of the boxes to the

subject screen touch to select the colour on which to

gamble. This is calculated across all assessment trials.

-ve ms 0-00

CG

T

Delay

aversion

Reflects an inability or unwillingness to wait, betting

larger amounts when the points to bet are presented in

descending order than when amounts are presented in

ascending order. Calculated by subtracting the mean

proportion bet on ascending gamble trials from the

mean on descending trials. Calculated for non-practice

trials only.

Complex

– higher

shows

more

delay

aversion

-0.9-

0.9

CG

T

Overall

proportion bet

The mean proportion of current points gambled by the

subject on all assessment gamble trials.

Complex

– lower is

‘more

self-

controlle

d’

0-1

Intra-Extra Dimensional Set Shift


IED Pre-ED

Errors

This metric records the number of errors made prior to the

extra-dimensional shift of the task. Errors are defined as

instances when the subject fails to select the stimulus that

is compatible with the current rule.

+VE 0-27

IED EDS Errors made in the extra-dimensional stage of the task are 0-27

24


Errors labelled EDS errors as they have been committed at the

stage where the subjects is required to make an extra-

dimensional shift. Errors committed at the reversal stage

following the EDS stage are not included.

IED IED Total

errors

This is a measure of the subject's efficiency in attempting

the test. Thus, whilst a subject may pass all nine stages, a

substantial number of errors may be made in doing so. It is

crucial to note that subjects failing at any stage of the test

by definition have had less opportunity to make errors - the

IED Total errors (adjusted) measure attempts to

compensate for this.

+ve 0-1

IED IED Total

errors

(adjusted)

This is a measure of the subject's efficiency in attempting

the test. Thus, whilst a subject may pass all nine stages, a

substantial number of errors may be made in doing so. It is

crucial to note that subjects failing at any stage of the test

by definition have had less opportunity to make errors.

Therefore, this adjusted score is calculated by adding 25

for each stage not attempted due to failure. This value of 25

is used since subjects must complete 50 trials to fail a

stage and half of these could be correct by chance alone.

+ve -1-1

IED IED

Completed

stage

errors

This is errors made on stages sucessfully completed.

Subjects failing at any stage of the ID/ED shift will have

less opportunity to make errors than those who finish, or

get closer to finishing, the task. It would therefore be

misleading to simply compare errors made in

circumstances where different stages were reached (see

IED total errors (adjusted)).

-ve ms 0-00

IED IED errors

(block 1)

This is the total number of errors made in block 1, only

when one perceptual dimension is present. Failure at this

stage of the task indicates impairment in simple

discrimination learning.

+ve 0-1

IED IED errors

(block 2)

This is the total number of errors made in block 2. This

measure, taken together with IED errors (blocks 5, 7 and

9), provides a good measure of reversal learning and can

be sensitive to impairment shown in disorders such as

frontal variant frontotemporal dementia (fvFTD) (Rahman et

+ve -1-1

25


al (1999) Brain 122 1469-1493).

IED IED errors

(block 3)

This is the total number of errors made in block 3, when

two perceptual dimensions are present (shape and line),

but they are not truly ‘compound’ (the two dimensions are

physically and perceptually separated).

-ve ms 0-00

IED IED errors

(block 4)

This is the total number of errors made in block 4, when

two perceptual dimensions are present and one has been

superimposed on the other – they are ‘compound’.

+VE 0-27

IED IED errors

(block 5)


measure, taken together with IED errors made at blocks 2,

7 and 9, provides a good measure of reversal learning and

can be sensitive to impairment shown in disorders such as

fvFTD (Rahman et al (1999) Brain 122 1469-1493).

0-27

IED IED errors

(block 6)

This is the total number of errors made in block 6; the

number of errors taken to successfully complete an

interdimensional shift (the shift of attention to a novel

exemplar within a previously relevant perceptual

dimension). Taken together with performance at the

extradimensional shift, IED errors (block 8), these two

measures give a good indication of attentional ‘flexibility’.

+ve 0-1

IED IED errors

(block 7)


measure, taken together with IED errors (blocks 2, 5 and 9,

provides a good measure of reversal learning and can be

sensitive to impairment shown in disorders such as fvFTD

(Rahman et al (1999) Brain 122 1469-1493).

+ve -1-1

IED IED errors

(block 8)

This is the total number of errors made in block 8: the

number of errors taken to successfully complete an

extradimensional (ED) shift (the shift of attention to a novel

exemplar of a previously unrewarded perceptual

dimensions). Taken together with performance at the

intradimensional (ID) shift, IED errors (block 6), these two

measures give a good indication of attentional ‘flexibility’.

Performance at this stage is sensitive to cognitive deficits in

Parkinson’s disease (see Downes et al. (1998)

Neuropsychologia, 27, 1329-1343) but can also be

sensitive to pharmacological manipulation of dopamine

-ve ms 0-00

26


function by, for example, sulpride (Mehta et al (1999)

Psychopharmacology, 146 (2) 162-74.

IED IED errors

(block 9)


measure, taken together with IED errors (blocks 2, 5 and 7,

provides a good measure of reversal learning and can be

sensitive to impairment shown in disorders such as fvFTD

(Rahman et al (1999) Brain 122 1469-1493).

+ve 0-1

IED IED

Stages

completed

There are nine stages to be completed in this task in the

clinical setup. Subjects completing all stages are deemed

to have 'passed the test'. There are two key stages, the

intra-dimensional shift (stage 6) and the extra-dimensional

shift (stage 8). Analysis of stage reached has often been

conducted using the likelihood ratio method for contingency

tables which yields a likelihood ratio statistic '2i' (for further

details of this analysis see Robbins, T. 1977 in Iversen, LL.

et al. (Eds.) The Handbook of Psychopharmacology. Vol. 7,

pp. 37-82, Plenum Press New York).

+ve -1-1

IED IED Total

trials

This is the number of trials completed on all attempted

stages. Note that subjects failing at any stage of the test

have had less opportunity to complete trials - the IED Total

trial (adjusted) measure attempts to compensate for this.

-ve ms 0-00

IED IED Total

trials

(adjusted)

This is the number of trials completed on all attempted

stages. The adjustment adds 50 for each stage not

attempted due to failure at an earlier stage.

-ve ms 0-00

IED IED

Completed

Stage

trials

This is the number of trials on all successfully completed

stages.

-ve ms 0-00

27

3.5 Data Backup

Open the CantabEclipse software and chose “Analyse results” - Then display all test results by

changing the filter to the start of the study. You are then provided with an overview of all data sets

acquired since the start of the study.

Search for test results of the respective volunteer (If date of birth of the participant has not been

entered before please include this information: Mark one of the tests obtained from one

participant, click on the button edit subject and insert the date of birth and click ok). Select all

data gained from a single subject (by marking them with the mouse; remember to only select

the FU3 run)

Save the files (rawdata, datasheet, report & detailed datasheet) in the folder “Imagen_Data_FU3”

under My Documents and label the file by the Subject’s 12-digit PSC1 code. If no such folder

exists, please generate a new folder with this name the first time you are saving data. Save all

future data in this folder.

Generate and save output files for one volunteer

Generate and save RAWDATA (cclar files)

• File -> Exported selected to archive

• Save file as cant_ <PSC1>FU3 (e.g. cant _010000002002FU3)

Generate and save DATASHEET (csv files)

• Under Analysis select Summary data

• Select Recommended measures datasheet (including new tests) (do not use the

imagen_template_datasheet)

• Select please generate ‘DATASHEET’ containing the following columns

• Save to file -> save with following name datasheet _<PSC1>FU3 (e.g. datasheet

_010000002002FU3)

Generate and save REPORT data (html files)

• Under Analysis select Summary data

• Select imagen_template_report (pick respective template file you have saved before)

• Select please generate ‘REPORT’ containing the following columns

28

• Please check that the following options are chosen: Include norm comparisons (15 as

minimum size of comparison peer group (N); child as normative reference database; force

widening on: gender).

• Save to file -> save with following name report_<PSC1>FU3 (e.g. report_010000002002FU3)

Generate and save DETAILED DATASHEET (csv files)

• Under Analysis select ‘Save detailed datasheet’

• Save to file -> save with following name detailed_datasheet _<PSC1>FU3 (e.g.

detailed_datasheet _010000002002FU3)

Please back up the data onto another computer in addition to saving the data on the CANTAB.

And refer to section 2.3.4 for information on how to transfer the data to Neurospin.

*Note: It is imperative that the files are saved with the correct 12-digit PSC1 code followed by FU3 (capital letters). No other format will be accepted into the Neurospin database.

4 Psytools Institute Assessments Note: If you have a barcode scanner, please ensure that the PSC1 codes are scanned into

the Psytools Institute to avoid any errors.

4.1 Passive Avoidance Learning Paradigm (PALP) Adapted from the WinGo task under direction from Natalie Castellanos (IoP, London).

4.1.1 Overview

This Go/No Go task is an experimental method for investigating passive avoidance learning and

behavioral disinhibition in humans. Passive avoidance is defined as the ability to withhold a

response that would have led to punishment. In this task subjects must learn by trial and error to

response to “good” numbers for monetary reward and withhold response to “bad” numbers to

avoid punishment (loss of money) (Arnett and Newman, 2000).

Series of numbers appear on the screen, subject has to decide if they should respond or not.

Some numbers should be responded to other should not. The subject has to learn which is which.

A running score is always displayed and the reward and punishment involve the increase or

decrease of the score- they are informed that the score will influence a real monetary reward at

29

the end of testing. All responses are made using the space bar. The task is run under three of the

possible four reward contingencies –

• RP (responding to a “right” or active number is Rewarded and responding to a “wrong” or

passive number is Punished)

• RR (“right” responding to an active number is Rewarded and correctly missing a “wrong”

or passive number is Rewarded)

• PP (missing a “right” or active number is Punished and responding to a “wrong” or

passive number is Punished)

4.1.2 Introduction Each condition is preceded with 3 practice blocks using the stimuli 1 and 2. In the first block the

subject is forced to respond to every trial to see which stimuli is right/wrong and whether this is

rewarded or punished. In the second block the subject is forced to not respond to any trial to see

how this affects the reward/punishment. In the third block the subject is able to choose whether to

respond or miss each trial. After the introduction the subject is offered the chance to repeat it.

4.1.3 Main Test First the subjects see a “pretreat” block – this is to help them learn which stimuli is right/wrong. It

contains two trials of each “right” stimuli and one trial of each “wrong” stimuli, presented in a

random order. Then follows 10 test blocks, each one contains one trial for each stimuli presented

in a random order.

4.1.4 Trial Timeline 0 ms - Clear Screen.

0 ms - Response window opens.

0-3000 ms - Stimulus displayed centrally.

3000 ms - Response window closes.

3000 ms - Erase stimulus.

3000 ms - Feedback presented if necessary.

3000-4000ms – ITI

30

4.2 SRC

4.2.1 Overview The SRC task was introduced by De Houwer et al. (2001). It aims to measure the affective Simon

effect. This effect occurs when someone is inclined to respond in a certain way to a stimulus, i.e.

faster for congruent than for incongruent responses. For example: someone that would like to

drink alcohol would be more inclined to respond to an alcohol stimulus by approaching it

(congruent, faster response), than by avoiding it (incongruent, slower response).

31

5 Time-Line-Follow-Back

The researcher is required to complete a diary with the participant to document the amount of

drug, cigarette, alcohol consumption, and medication intake in the past 30 days, not including the

institute assessment day. It also asks for the amount of money the participant spent on the

drug/alcohol/cigarettes.

Additionally please register the drug, alcohol, cigarette and medication use on the day of the

institute visit as we will need to know whether the participant is suitable to be scanned. Some

drugs have effects on the individual that mean performing a functional MRI scan would be

inappropriate.

Please ensure you are conducting this assessment in a confidential environment i.e. not in the

corner of a waiting area. Remind your participant about confidentiality. Full instructions can be

found in section 8.3.1.

To facilitate recall the researcher needs to explain the diary sheets to the participant; show them

the 30 day calendar with TODAY marked into the appropriate place. The researcher then fills in

the calendar dates beginning with YESTERDAY as day 1 and counting back 30 days.

The researcher must ask the participant to recall as many potentially relevant events that have

happened during the past 30 days (e.g. bank holidays, regular courses etc), please record these

events first. Then return to day one of the calendar and document day-by-day the amount of

drugs/alcohol/cigarettes the participant consumed, as well as the amount of money the participant

spent on the substances.

At a later point in time, the results of the TLFB interview regarding the past 30 days (not including

today) will be summed and filled into the boxes in the last section of the TLFB sheets (see also

CRF). To calculate the number of Standard Drinks Units, an excel sheet is provided including a

formula containing the two variables; volume percentage of alcohol and the volume per drink.

Please ensure you use the excel sheet that pertains to your country. To calculate drug and

tobacco use, please see section 8.3.5. These data will then be entered into Psytools by the

researcher.

The TLFB data (and reliability) should be transferred to the database via Psytools, under the

participant Institute login.

32

6 Biological Sample Collection and Storage Please refer to the Biological Sample SOP that has been uploaded on Milliarium.

Please ensure that you contact the participant to remind them not to use hair dyes, bleach or anti-

dandruff shampoo on their hair for at least 3 days prior to institute visit.

7 Mini-International Neuropsychiatric Interview (MINI)

7.1 Overview of the MINI modules:

M.I.N.I. 5.0.0 / English version / DSM-IV / current MODULES TIME FRAME

A. MAJOR DEPRESSIVE EPISODE Current (past 2 weeks) + Lifetime

A’. MDE with melancholic features Current (past 2 weeks) (Optional)

B. DYSTHYMIA Current (past 2 years)

C. SUICIDALITY Current (past month)

D. (HYPO) MANIC EPISODE Current + Lifetime

E. PANIC DISORDER Lifetime + current (past month)

F. AGORAPHOBIA Current

G. SOCIAL PHOBIA Current (past month)

H. OBSESSIVE-COMPULSIVE DISORDER Current (past month)

I. POSTTRAUMATIC STRESS DISORDER Current (past month) (Optional)

J. ALCOHOL DEPENDENCE / ABUSE Current (past 12 months)

K. DRUG DEPENDENCE / ABUSE (Non-alcohol) Current (past 12 months)

L. PSYCHOTIC DISODERS Lifetime + Current

M. ANOREXIA NERVOSA Current (past 3 months)

N. BULIMIA NERVOSA Current (past 3 months)

O. GENERALIZED ANXIETY DISORDER Current (past 6 months)

P. ANTISOCIAL PERSONALITY DISORDER Lifetime (Optional)

7.2 General Instructions

The M.I.N.I. was designed as a brief structured interview for the major Axis I psychiatric disorders

in DSM-IV and ICD-10. Validation and reliability studies have been done comparing the M.I.N.I. to

the SCID-P and the CIDI. The results of these studies show that the M.I.N.I. has acceptably high

validation and reliability scores, but can be administered in a much shorter period of time (mean

33

11.6 – 18.7 min., median 15 min.) than the above referenced instruments. It can be used by

clinicians, after a brief training session. Non-clinicians will require more extensive training.

Interview: In order to keep the interview as brief as possible, inform the patient that you will

conduct a clinical interview that is more structured than usual, with very precise questions about

psychological problems which requires a yes or no answer.

General format: The M.I.N.I. is divided into modules identified by letters, each corresponding to a

diagnostic category. At the beginning of each module (except for psychotic disorders module),

screening question(s) corresponding to the main criteria of the disorder are presented in a gray

box. At the end of each module, diagnostic box(es) permit(s) the test administrator to indicate

whether the diagnostic criteria are met.

7.3 Conventions

Sentences written in « normal font » should be read exactly as written to the patient in order to

standardize the assessment of diagnostic criteria. Sentences written in « CAPITALS » should

not to be read to the patient. They are instructions for the interviewer to assist in the scoring of

the diagnostic algorithms. Sentences written in « bold » indicate the time frame being

investigated. The interviewer should read them as often as necessary. Only symptoms occurring

during the time frame indicated should be considered in scoring the responses. Sentences (in

parentheses) are clinical examples of the symptom. These may be read to the patient to clarify

the question. Answers with an arrow above them ( ) indicate that one of the criteria necessary

for the diagnosis(es) is not met. In this case, the interviewer should go to the end of the module,

to circle « NO » in all the diagnostic boxes and move to the next module. When terms are

separated by a slash (/), the interviewer should read only those symptoms known to be present in

the patient (for example, question A3).

7.4 Rating instructions:

All questions read must be rated. The rating is done at the right of each question by circling either

YES or NO. The clinician should ensure that each dimension of the question is taken into account

by the patient (i.e.: time frame, frequency, severity, « and/or » alternatives). Symptoms better

accounted for by an organic cause or by the use of alcohol or drugs should not be coded positive

in the M.I.N.I.. The M.I.N.I. Plus has questions that investigate these issues.

34

8 Wechlser Adult Intelligence Scale (WAIS)

8.1 Overview The WAIS-IV is a battery of tests that provides an estimate of general intellectual functioning.

Intelligence tests like this one are samples of problem solving abilities and learned facts, and are

good predictors of future learning and academic success.

The WAIS-IV has 10 core subtests, which make up four index scores, including the Verbal

Comprehension Index (VCI), the Perceptual Reasoning Index (PRI), the Working Memory Index

(WMI), and the Processing Speed Index (PSI). These 4 subsets being included in the Institute

Assessment at Follow-up 3 are: Block Design, Similarities, Vocabulary, and Matrix Reasoning.

Participants were assessed at baseline using these four subsets with the WISC, the child-

compatible version of the WAIS.

8.2 Test Instructions Follow the instructions in the manual. A free webinar and PPT/PDFs of resources can be found at

http://www.pearsonclinical.com/psychology/products/100000392/wechsler-adult-intelligence-

scalefourth-edition-wais-iv.html#tab-training.

8.2.1 Block Design It measures the ability to analyze and synthesize abstract visual stimuli. Working within a

specified time limit, the examinee views a model and a picture, or a picture only, and uses red-

and-white blocks to recreate the design.

8.2.2 Similarities It measures verbal reasoning and verbal concept formation. The examinee is presented two

words that represent common objects or concepts and describes how they are similar. For

example: "Now I am going to say two words and ask you how they are alike. How are ….. and

…..alike? How are they the same?"

8.2.3 Vocabulary It measures word knowledge and verbal concept formation. For picture items, the examinee

names the object presented visually. For verbal items, the examinee defines words presented

35

visually and orally. As a 'picture' item example: "What is this?". As a 'verbal' item example: "I am

going to say some words. Listen carefully and tell me what each word means."

8.2.4 Matrix Reasoning It measures fluid intelligence, spatial ability, perceptual organization and simultaneous

processing. The examinee views an incomplete matrix or series and selects the response option

that completes that matrix or series.

36

9 APPENDIX

9.1 Neuroimaging

fMRI Instructions to participants (ENGLISH):

In the following scanning session we will ask you to perform different tasks and games; they are

the same ones you have performed ~4 years ago during your second follow-up assessment. We

would like to go through these tasks and games first outside the scanner using this standard

computer. Additionally you have the opportunity to practice some of the tasks. Let’s start with a

few simple tasks which target basic functions of the brain.

Monetary Incentive Delay Task (MID Task)

This task is a reaction time task - it tests how quickly you can press the button to hit a target,

which is a white square appearing only for a short time on the left or right of the screen. If you

manage to press the button as soon as the white square appears, you will score points. If you

respond too early (before the white square appears) or too late (after the white square has

disappeared) you will not gain any points. You can tell where the white square will appear and

how many points you will win by the symbol you see on the screen before the white square is

shown. A triangular symbol means you will not win any points, a circle with a line means you will

win 2 points and a circle with three lines means you will win 10 points. You should try to win as

many points as you can! - but only if you press the button while the square is presented on the

screen! Your points will be exchanged for cash/vouchers, let’s see how much you can win!

Face task

In this task you will be presented with short video clips showing faces with neutral, happy and

angry expressions as well as moving circles. Please watch them carefully and remember to lie as

still as possible during this task.

Stop-signal task In this task you will be presented with a picture of an arrow pointing left, or a picture of an arrow

pointing right. You must respond by pressing the button with your left index finger if the arrow is

pointing to the left and with your right index finger if the arrow is pointing to the right. It is

important that you react as quickly as possible. Occasionally, the arrow pointing left or right will

be followed by an arrow pointing upwards. If this happens, you must not respond at all, rather you

must try and refrain from reacting. Of course, you will not always be able to stop yourself from

37

responding when this happens. Please do not wait to see if the upwards arrow is going to appear,

the task is designed to allow for these mistakes.

Resting State: This task uses no visual or auditory stimulation. Please keep your eyes closed,

relax, refrain from moving and please stay awake.

Acquisition Protocol

VERY IMPORTANT NOTE: The procedures for operating of the MRI console are described in the

baseline “Neuroimaging Standardization SOP” (WP 05). They are relevant for FU3 and the

document for each site can be found on Milliarium (22_WP Documents > WP05 Neuroimaging

standardization > Imaging SOPs). However, the FU3 acquisition parameters are the same as for

FU2, which were different from baseline. The acquisition parameters described in this section are

MANDATORY for FU3.

The neuroimaging acquisition protocol is based on the 2012 MRI Quality Control acquisition

protocol, which was developed using the baseline acquisition protocol as a reference.

Functional Sequences:

- Monetary Incentive Delay Task (MID)

No. of Volumes 191

TR 2.2

TE 30

Flip Angle 75

No. of Slices / DDAs 40 / 3

Slice Thickness 2.4

Slice Gap 3.4

Voxel size 3.4x3.4x2.4

Matrix Size 642

FOV 218

38

- Face task (FT)

No. of Volumes 202

TR 2.2

TE 30

Flip Angle 75


Slice Thickness 2.4

Slice Gap 3.4


Matrix Size 642

FOV 218

- Stop-signal task (FT)

No. of Volumes 349

TR 2.2

TE 30

Flip Angle 75


Slice Thickness 2.4

Slice Gap 3.4


Matrix Size 642

FOV 218

39

- Resting State (RS)

No. of Volumes 164

TR 2.2

TE 30

Flip Angle 75


Slice Thickness 2.4

Slice Gap 3.4


Matrix Size 642

FOV 218

Structural Sequences:

- 3D Sagittal ADNI MPRAGE (Long)

Siemens (3T) GE (3T)

Orientation sagital sagital

Slice Thickness 1.1 1.1

Slice Gap 1.1 1.1

TE 2.93 2.812

TR 2.3 6.608

TI 900 900

No. of Slices 160 166

Matrix Size 2562 2562

FOV 280 280

For ADNI MPRAGE, please set z=0 according to the red cross in the figure below.

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- Axial T2 slices (optional)

- Axial T2 Flair slices (optional)

- DTI (un-gated in the Siemens sites; gated in the GE sites)


TR 15 s 17.6 s

TE 104 104

Flip Angle - 90

No. of Slices 60 60

Slice Thickness 2.4 2.4

Slice Gap 2.4 2.4

Matrix Size 1282 1282

FOV 307 307

41

- NODDI (parameters to be decided by August/early September)


TR x y

TE x y

Flip Angle x y

No. of Slices x y

Slice Thickness x y

Slice Gap x y

Matrix Size x y

FOV x y

42

9.2 CANTAB

CANTAB Instructions:

Now I’d like to ask you to take part in different computer games. They could appear to be a bit

different than the ones you might be used to. They are on the one hand demanding but also fun.

Some of them will challenge your memory and patience, some of them will just ask you to make

your best guess. We will have a closer look at them one by one. Do you have any questions so

far?

43

1) Spatial Working Memory - SWM - (p. 155)

48

2) Cambridge GUESSING Task - CGT - ascending first-2s (p. 46)

52

3) Intra-Extra Dimensional Set Shift (p. 69)

54

9.3 Passive Avoidance Learning Paradigm (PALP) PALP Instructions for Participants

For all tasks

1. There are three conditions of this Numbers Task. Each condition differs from the other

two in how you can win points. Therefore, please read the instructions carefully for every

condition.

2. In this task, you're going to see a series of numbers flash in the middle of the screen, one

at a time. Some of these numbers will be designated as “right,” and others will be

“wrong.” Your job will be to PRESS THE SPACE BAR for the RIGHT NUMBERS ONLY.

3. You will have to figure out WHICH NUMBERS ARE RIGHT and WHICH NUMBERS ARE

WRONG by trial and error. To figure this out, try pressing or not pressing THE SPACE

BAR when a number comes up and see what happens.

4. In order for your response to count, you'll have to press quickly, while the number is still

on the screen.

5. You'll have the opportunity to win points – the goal is to try and win as much as you can!

6. First, there is a practice trial to show you what happens by pressing and not pressing the

SPACE BAR in response to the numbers. Now let’s start with the practice for this

condition - your score does NOT matter yet.

RP:

For this condition, if you PRESS for a RIGHT number, you'll win 5 points. If you PRESS for a

WRONG number, you’ll lose 5 points. If you DON’T PRESS for ANY of the numbers, you won't

win or lose any points. Let's do some practice trials.

First, I want you to press for each of the numbers and see what happens…

So, it should be clear which number was right (“1”) and which was wrong (“2”). Notice that you

won points by pressing for “1”, but lost when you pressed for “2”.

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Now, DON’T PRESS for any of the numbers and see what happens …

Notice that you didn’t win or lose any points, but you know from the last trial that you could have

won points by pressing for “1”.

Now, try to press for the right number and don't press for the wrong number and see what

happens …

Notice that you won points by pressing for the right number (1) and that by not pressing to the

wrong number (2), you didn't lose any points. In the real task, the numbers will be different and

there will be more to remember – Basically, you need to remember which are the right and wrong

numbers. Let’s try the real thing now…

PP:

For this condition, if you DON’T PRESS for a RIGHT number, you’ll lose 5 points. If you PRESS

for a WRONG NUMBER, you’ll also lose 5 points. If you PRESS for the right number, or you

DON’T PRESS for the wrong number (i.e., if all your responses are correct), you won’t win or lose

any points – so nothing will appear on screen (no feedback).


So, it should be clear which number was right (“1”) and which was wrong (“2”).¬Notice that you

did not win points by pressing for “1”, but lost when you pressed for “2”.


Notice that you lost points by not pressing for “1”, but did not lose when you not pressed for “2”.

Let’s do it properly this time. PRESS for “1” and DON’T PRESS for “2” and see what happens …

Notice that you don’t win or lose any points when all your responses are correct. On the real task,

you’ll be given some points at the beginning, and you should try to keep as much of it as possible.

In the real task, the numbers will be different and there will be more to remember – Basically, you

need to remember which are the right and wrong numbers. Let’s try the real thing now…

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RR:

In this condition, if you PRESS for a RIGHT number, you’ll win 5 points. If you DON’T PRESS for

a WRONG number, you’ll also win 5 points. If you DON’T PRESS for a RIGHT number, or you

PRESS for a WRONG NUMBER, (i.e., if all your responses are incorrect) you won’t win or lose

any points. Let’s do some practice trials.


So, it should be clear which number was right (“1”) and which was wrong (“2”).¬Notice that you

won points by pressing for “1”, but did not lose when you pressed for “2”.


Notice that you did not lose points when you did not press for “1” and won when you did not press

for “2”.

Let’s do it properly this time. PRESS for “1” and DON’T PRESS for “2” and see what happens …

Notice that you won points each time by pressing for “1” and not pressing for “2”. In the real task,

the numbers will be different and there will be more to remember – Basically, you need to

remember which are the right and wrong numbers. Let’s try the real thing now…

9.4 Timeline Follow Back (TLFB) We have composed some guidance for how we are dealing with the notion of ‘rounds’; when one

person buys the drinks for the entire table and the favour is reciprocated throughout the drinking

session. For the TLFB we are particularly interested in how much the participant spends on a

substance e.g. alcohol, that they consume themselves, their ‘personal engagement’ in the

substance ingestion. So if a person recalls spending £30 on an evening in the pub with their

friends, and they were the recipient of drinks as part of rounds then we would recommend you

score this as follows:

Calculate how much the individual would have spent on their own drink(s) in the round they

purchased and only include this in your scoring. We are not interested in how much the

participant invested in getting other people drunk!

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For situations where the type and amount of alcohol ingested was unknown e.g. ‘punch’ please

just try and get the best estimate the participant can give. So ask about size of the cups, what

type of alcohol they could taste (if they could) etc.

9.4.1 Administration Script Please follow the bold script verbatim where possible. In addition we have included questions to

help you elicit the maximum amount of information from you participants. This script is nearly

exactly the same as the one we used at baseline; however we have made it a little more

structured to help you administer it. Some researchers felt it was a little difficult to follow during

the baseline assessment.

This interview is going to focus on an evaluation of substance use; please be reassured that everything you tell me will be kept strictly confidential. To help us

evaluate your drinking, smoking and drug use as well as your intake of medication,

we need to get an idea of what your use has been like over the last 30 days. We

are also especially interested in your drinking, smoking and drug use, as well as

your intake of medication today.

So have you ever (in your lifetime) drunk alcohol, smoked tobacco (including e-

cigs), used drugs or taken any medication? <Wait for participant to answer> Yes/No

Thank you very much <enter answer onto sheet in CRF>.

If no – just check again with participant;

Are you sure? We do count the experiences of people who might have taken just a

sip of alcohol or an aspirin or a paracetamol for a headache.

If still no thank the participant very much and cease interview.

And may I ask now if you have [drunk alcohol/smoked tobacco(including e-

cigs)/used drugs/taken medication] in the last 30 days? <Wait for participant to

answer> Yes/No Thank you very much <enter answer onto sheet in CRF>. If yes,

proceed with interview as below.

Have you taken any medication today? <Wait for participant to answer> Yes/No

Thank you very much

If yes –May I ask what medication you have taken?

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Record as much detail as possible; if females have taken the oral contraceptive pill ask the brand

name, if they say something like ‘a painkiller’ ask what kind? If they are unsure try and prompt

their memory;

Did you buy it from a shop or did your doctor need to prescribe it to you?

Do you know if it was paracetamol/aspirin/ibuprofen/codeine?

Do you know the brand name of the painkiller you took?

How many tablets did you take?

How much did you pay for the paracetamol/aspirin/ibuprofen/codeine/cold and flu

remedy?

The idea here is that we can get an idea of the number of milligrams the person has ingested. If

they have the box with them please use it as a prompt, or perhaps they remember the dosage

instructions.

Have you taken any drugs today? <Wait for participant to answer> Yes/No Thank you

very much

If yes May I ask you what kind of drug you took today?

Again record as much detail as possible; for most drugs it would be unsuitable to perform the

neuroimaging session as their performance will most likely be affected – check with your local

team of radiographers if this is the case, but it is likely you will need to reschedule the scanning

session.

By this point you will know whether you need to fill out the whole calendar – it’s quite likely at this

age so be prepared to leave enough time to complete the assessment properly; we recommend

allowing up to one hour.

The idea for the text below is for you to tailor the assessment to the participant – so if they have

only reported smoking cigarettes ONLY refer to the fact that they have smoked cigarettes, there

is no need to refer to drinking or drug taking if they have not done it.

Ok, so as you have reported <smoking tobacco/drinking alcohol/drug use> in the last

30 days we are going to complete this calendar <show the example calendar to the

participant>. The idea is to fill out each day of the calendar – so on the days where you did not <drink alcohol/smoke cigarettes/take drugs/take medication> we will write a

zero (0) on the calendar. On the days where you did <drink alcohol/take drugs/take

59

medication> we’re going to record the type <give an example if you can – so a glass of

wine or a pint of beer, for example> and the amount you <drank/smoked/took>. We’re

also interested in the amount of money you spent on the <cigarettes/alcohol/drugs>

so if you paid for <the drinks/cigarettes/drugs> then we would also like to record that too.

We realise it isn’t easy to recall these things completely (or 100%) accurately, so if

you’re not sure if you had four or five pints of beer, or seven or eight cigarettes, or

if this was on a Thursday or a Friday then just give us your best estimate. What is

important is that seven or eight <drinks/cigarettes etc.> is very different to one or

two, and spending £5 is very different to spending £50.

At this point pull out the blank calendar and show it to the participant. The best way to fill out this

calendar is to start by putting in special one off events first, then asking about regular events the

participant might be engaged in, for instance sporting activities like playing football each week or

going to the gym. You could add on days when the participant went to work, or lectures –

anything they do regularly to jog their memory. Add on social events like parties they might have

attended. You could also ask if the participants have had any deadlines recently and if they

celebrated, e.g. had a presentation at work or handed in an essay at university/college. It’s a

good idea to ask the participant to bring their diary/iPhone/Android/organiser with them when

you’re booking their appointment – explain that it will help them to complete one of the

assessments.

When you’re completing the calendar write ‘TODAY’ in the last row – for example if the participant

has come for their assessment on Friday, write TODAY in the Friday box of the last row. Count

back from that day 30 days and fill out the date in each cell.

Record EVERYTHING no matter how nominal the amount seems! This includes ‘sips’ of alcohol

and ‘puffs’ of tobacco/drugs and importantly if they paid for the ‘sip’ or ‘puff’!

As you are recording what the participant is saying, bear in mind the way the data is entered

afterward. In particular, keep in mind the way the quantities are recorded, for example if grams or

tablets, and try to ascertain how much the participant consumed.

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9.4.2 Example Prompts/Questions

EXAMPLE ONE: If the participant reports smoking cannabis you could ask the following

questions:

o How much did you smoke?

o Did you smoke a joint?

o Did you smoke the joint with tobacco? <in which case, try to calculate the amount of

tobacco the participant would have consumed with cannabis>

o Did you smoke a pipe/bong/bucket/lung/blowback?

o Did you eat it?

o Did you smoke it on your own or did you share it?

o Did you pay for the cannabis?

o How much did you spend on buying it?

o How many joints would that amount of cannabis usually make you?

That way you could calculate cost per joint – If they shared the joint ask them how many puffs

they had, and whether they contributed to the cost. Remember that you are trying to get an

estimate in terms of grams so if the participant knows how many grams they bought and

consumed, you do not need to know the number of joints they had. Please try your hardest to get

an estimation of the amount and cost – this is very important.

EXAMPLE TWO: If the participant reports smoking cigarettes you could ask the following

questions:

o Are you a regular smoker?

o Do you pay for your cigarettes?

o What brand of cigarettes do you smoke?

<If you know the brand you can work out the cost per pack for your country> If the participant is a

regular smoker it might be more difficult to get an estimate of exactly how many cigarettes per

day they smoke but most people will be able to give you an estimate e.g. 4-5 per day. Perhaps

take them through a ‘typical’ smoking day so:

o Do they smoke when they wake up?

o How many cigarettes do they smoke before they leave the house?

o Do they smoke while they’re waiting for the bus/train or walking to work?

o Do they have a cigarette in a particular place before work/university?

o Do they take cigarette breaks? E.g. between lectures, or as part of a working day?

o Are there some times when they smoke more than others?

For instance if they are in a social group or perhaps if they are watching a sporting event (e.g.

some people get ‘stressed’ watching football!), perhaps when they’re in a bar/pub they smoke

61

more. Asking detailed questions like this will mean you get good data and the participant gives

you more accurate answers.

EXAMPLE THREE: If the participant reports drinking alcohol you ask the following questions as

suggested for the other examples. If the participant reports drinking wine, find out what type:

o Was it a red, white or rose?

o Did they have one glass or 5?

o What size was that glass?

o Were they in a bar/pub/restaurant or at home?

o Did they share a bottle with a friend?

All of these questions should help you to work out how much money they spent on the alcohol.

EXAMPLE FOUR: Participant reports taking Class A drugs, for instance cocaine, you could ask

the following questions:

o Did you buy the drug yourself?

o How many grams did you buy?

o How much did it cost you?

o Did that amount last you one night out or more than one?

o Did you take it all yourself or did you share it with any of your friends?

o How many lines did you take?

o From the total amount you bought how much did you take/how much was left?

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9.4.3 Local Help per Site/Country

In London we have made a list of types of alcohol to help prompt us researchers and also to help

us accurately record the different kinds of alcohol – it’s easier for us to check/estimate the price

too that way if the participant is unsure. Please make such a list for your site if you feel it is useful.

Snakebite: half lager half cider with blackcurrant cordial popular with university students

Jaegerbomb: shot of Jaegermeister dropped into energy drink e.g. Redbull

Turboshandy: Smirnoff ice mixed with lager

Swizzle: whiskey, soda/lemonade and lime

Cheeky vimto: port mixed with smirnoff ice and blue wkd

Chinese: half a lager mixed with half a bitter

Red wine mixed with coke

Black velvet: Guinness mixed with champagne/prosecco/cava

Knockout: Guinness mixed with vodka

Centurian: 100 shots of beer in 100 minutes

Gin and Tonic

Vodka and…..

Rum and coke

Prosecco/champagne/cava

Bitter: London pride, doom bar, john smiths, bombardier

Lager: Fosters, Carlsberg, Heineken, Stella Artois, Carling Black Label, Becks, Coors, Budweiser

Premium lager: Peroni, Leffe, Hoegarden

9.4.4 Example Calendar

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9.4.5 Scoring the TLFB

The following bullet points will help you to score alcohol consumption in the TLFB.

• Try and get as much detail as you possibly can e.g. size of glass, if a mix what was the

mix made of? If in doubt please do not hesitate to ask the participant what the type of

drink was made of.

• If the participant cannot tell you exactly what the drink is made of or the quantity, ask for

the best guess/ estimate possible.

• Once you have this, you must follow the protocol for scoring TLFB, i.e. the first reference

should always be the Standard drink unit chart. This should have most of the drinks listed

and the quantity stated.

• In case the drink is not listed please Google it and check what the percentage volume is.

Also different brands of alcohol will have different strengths - for instance, different makes

of gin have different percentage volume, it may also vary in different countries.

• Also bear in mind that the glass sizes may differ in different countries.

• Once you have all this information you must refer to the chart – for example, if the

participant had one small glass of white wine:

a) Check if the listed alcohol and glass measure is listed in the SDU sheet.

b) If yes you can proceed to that row and see the column where it states times, in this

instance it is only one glass so you enter 1 and the press the enter key. The result

column will show you the calculated SDU.

If you do NOT have a drink which is listed in the SDU sheet then you should:

• Google the volume of the glass used if it not standard glass.

• Check what the drink is made of in this case, if it was a mixer or a punch you find out

what went in the punch. For example it was made of ½ a bottle of peach schnapps

and half a bottle of red wine then you check online what the percentage volume of

each drink is.

• Make a new row in the SDU sheet for the different alcohol. Make sure you go to the

last the 3 columns of the row where you are adding the new drink and copy or drag

the formula from the previous row to the new one.

• In this instance if only half bottle of archers was used you can put .5 in the times

column and it will calculate it for you.

• This way you can get a total of all the days. You must keep in mind you also have to

calculate the total of the SDU consumed per day; the number of days where it is 5

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and above for boys or 4 and above for girls must be recorded on the scoring sheet

separately from the grand total of the 30 days.

Cigarettes and Drugs

The following bullet points will help you to score the cigarettes and other drugs sections in the

TLFB

• Try to get as much detail as possible when speaking to the participant; e.g. what type

of drug it was, how much it cost, how much they bought/consumed, exact details of

how they took the drug such as insufflating lines or swallowing dabs of powder.

• Most of the drugs are quantified in terms of grams; the exceptions being number of

cigarettes for tobacco, number of tabs/trips for LSD and number of pills for ecstasy

• For cigarettes, consider one hand-rolled cigarette to be equivalent to one pre-rolled

cigarette

• Feel free to ask about electronic cigarette usage. Currently, there is no unit

standardization. It's also hard for people to estimate their usage as the amount often

depends on the delivery system of choice and type of liquid used. Safe questions

include: how many times per day they use it, how many minutes per day they use it,

the length of each smoking session, and the approximate number of puffs per

session and per day.

• Tobacco consumed as part of a cannabis joint should be recorded in the ‘Tobacco’

section – if a participant had a joint that was half tobacco and half cannabis, the

tobacco may be recorded as 0.5 cigarettes

• Method of consumption is recorded for cannabis, heroin and narcotics so please be

mindful to ask participants how they consumed any of these drugs

• Note that there is a free text box in the Psytools sections for cannabis, inhalants,

prescription drugs, amphetamines and other drugs. This cannot be left blank, if

there is no information to add to the box, please write ‘n/a’ to indicate that the box is

not needed.

• The free text box is used to detail the exact method of consumption, unless specified

elsewhere, for example, 2 lines of cocaine, 4 ‘dabs’ of MDMA, 3 joints etc., or for any

other relevant information.

• In some instances it can be particularly hard to quantify the drugs taken in terms of

grams. Therefore it is recommended that in addition to an estimate of quantity, the

terms given by the participant are specified in the free text box. For example; 4 lines

of cocaine, 2 ‘dabs’ MDMA

• Cannabis is quantified in terms of grams and should be recorded as such. However,

on occasion a participant may report the amount of cannabis consumed in other

67

terms, e.g. no of joints, and will be unable to give an estimate in grams. In this case,

the researcher should report a ‘0’ in the gram box and then use the free text box to

detail the exact quantity and consumption method. For example; one small metal

double-chamber pipe shared evenly between four people; three inhalations of a joint

containing tobacco; one inhalation from a water bong.

• Any medication taken by the participant should be noted in the “Other Drugs”

section, with details of the name of the medication, amount taken and active

ingredients recorded in the free text box, e.g., “Lemsip Cold &Flu, 2 tablets taken,

ingredients: Paracetamol 500mg, Phenylephrine Hydrochloride 6.1mg, Caffeine

25mg per tablet”

• Hormonal contraception use is recorded elsewhere in Psytools, in NI Data

• The section named “prescription drugs” is for recording the consumption of

prescription drugs taken for an unintended use, e.g. taking Valium for recreational

purposes [Note that if the participant is taking codeine for recreational purposes, it is

recorded in the narcotics section]