EEG Patterns Analysis of Methadone Patients with Closed Eyes

Condition using Wilcoxon Test

Dwi Esti Kusumandari

, M. Faizal Amri

, Artha I. S.

, Rina Ristiana

, Maissy Jahja

and Arjon Turnip

Technical Implementation Unit for Instrumentation Development, Indonesian Institute of Sciences,

Komplek LIPI gedung 30, Bandung, Indonesia

Department of Physical Engineering, Telkom University, Bandung, Indonesia

Department of Electrical Engineering, Padjadjaran University, Bandung, Indonesia

Keywords: Methadone, EEG, Brain Waves, Wilcoxon Test.

Abstract: This research was conducted to know the effect of methadone on brain waves before and after consuming

methadone with closed eyes and relaxed body conditions. EEG signal recording will use 19 channels, which

are placed using a 10-20 system. The raw data will be filtered using a bandpass filter (0.5 - 70 Hz), removal

of artifacts using the Independent Component Analysis (ICA) method, and feature extraction using the Fast

Fourier Transform method. Then a significant test will be carried out using the Wilcoxon test with a

significance value (accuracy) of 95% or p <0.05. The results were obtained, namely the effect of methadone

on brain waves with an average number of participants that is 14 people on alpha waves. Furthermore, each

wave occurs at a different recording stage.

1 INTRODUCTION

Methadone maintenance therapy is one of the stages

of rehabilitation for opioid drug users, such as

cocaine, heroin, marijuana, and others (Dewi, 2017).

This therapy is done to help addicts reduce the habit

of using needles (Kementerian Kesehatan RI, 2013).

This is because the methadone given is like a syrup,

so it must be consumed by mouth, not by injection.

To determine the effect of methadone, it is still seen

through changes in behaviour alone. This is not

accurate enough, because not all patients follow the

therapy properly and routinely. Several researchers

have researched about EEG recording to determine

the effect of methadone on patients during the

rehabilitation process.

EEG has been use since 1929 (Simbolon, 2019).

EEG is used to record the electrical activity in the

brain with electrodes placed on the scalp (Sanei,

2007). Usually, an EEG is used to look for

abnormalities in the brain, such as epilepsy. However,

now, EEG can be used to see the effects of drug on

the brain.

The electrical activity of the brain based on its

frequency is divided into delta, theta, alpha, and

gamma waves. Delta (δ) has a frequency range from

0.5-4 Hz and an amplitude of 20-200 μV. Delta waves

are generated in a state of deep sleep, without dreams

or what is commonly known as deep sleep. Theta (θ)

has a frequency range of 4-8 Hz and an amplitude of

10 μV. Theta waves are generated during light or very

drowsy sleep, trance, hypnosis, meditation. Alpha (α)

has a frequency range from 8-13 Hz and an amplitude

is normally below 50 μV. Alpha waves are generated

in a state of relaxation or begin to rest, going to sleep,

the transition between conscious and unconscious.

Beta (β) has a frequency range from 13-30 Hz and an

amplitude is normally below 30 μV. Beta waves are

generated when you are thinking, focused. Gamma

(γ) has a frequency range from 30-50 Hz. Gamma

waves are generated when a person feels panic,

fearful, and is in a state of full awareness. The brain

wave pattern of normal people can be seen in Figure

To determine the effect of methadone, several

researchers conducted studies on theta, alpha, and

beta waves (Jahja, 2019; Wang, 2014; Kusumandari,

2019; Gunawan, 2012; Uson, 2008). With the results

are that the used of methadone affect those three brain

waves. However, the data processing used was to see

the trend of these three waves in methadone

574

Kusumandari, D., Amri, M., S., A., Ristiana, R., Jahja, M. and Turnip, A.

EEG Patterns Analysis of Methadone Patients with Closed Eyes Condition using Wilcoxon Test.

DOI: 10.5220/0010339000003051

In Proceedings of the International Conference on Culture Her itage, Education, Sustainable Tourism, and Innovation Technologies (CESIT 2020), pages 574-578

ISBN: 978-989-758-501-2

maintenance therapy patients with normal people.

Besides that, some focus on the frontal part only

Figure 1: Brain wave pattern of normal people.

(Turnip, 2019; Turnip 2017). Based on this, this study

will focus on 4 waves, namely delta, theta, alpha, and

gamma to see the effect of methadone before and after

consuming methadone. The stage after consuming

methadone will be divided into 3 sessions, namely 10

minutes, 1 hour, and 3 hours after consuming

methadone. From 3 sessions after consuming

methadone, it will be compared with before

consuming methadone. The recording process will be

carried out with closed eyes and relaxed body

condition. It aims to help doctors find out which brain

waves have undergone significant changes to create

the right treatment for other brain waves as well.

2 METHOD

2.1 Participants

Participants used 30 men aged 25-45 years and have

a history of at least high school education. These

participants will be divided into 2 groups, namely 19

participants for methadone rehabilitation patients and

11 participants as control participants. The

methadone rehabilitation patient participants were

TRM of RS Hasan Sadikin, Bandung. The criteria

that a methadone patient participant must have is that

it has been more than 6 months and its regular use,

has been in a stabilized dose, which is above 60 mg,

is a THD patient (take-home doses), does not use

other types of drugs other than benzodiazepines for

the last 1 month, and do not have serious physical

illnesses, epilepsy, and organic mental disorders that

can make communication difficult.

2.2 Experiment

The experiment is carried out in the UNPAD Faculty

of Medicine treatment room, Bandung. Each

participant in a methadone rehabilitation patient will

undergo 2 recording stages, before and after

consuming methadone. During the recording process,

participants will be directed by the operator to be

relaxed, eyes closed, and minimize any unexpected

movements and eye blinks.

Experiments have been completed with ethical

clearance. Before the experiment, each participant

was required to take a urine test and fill out informed

consent. Then the subjects were interviewed by

medical team about the subject related with an abuse

of drug. During the recording, the subject was asked

to relax with closing eyes before, after 10 minutes,

one hour, and after three hours of methadone intake.

This time rule was chosen to identify the change of

brain activity to the given doses of methadone. It is

also predicted that after three hours, the craving has

been stopped as the methadone has effectively

functioning. The experiments were conducted in a

room that has been conditioned from the noise and

comfort with the subject. Then the subject is paired

with a device in the form of an electro-cap on the head

and also a belt tied to the chest of the subject such that

the electro-cap is fit with the subject body. The EEG

signals are recorded through 19 electrode channels,

including Fp1, Fp2, F7, F3, F2, F4, F8, T3, C3, Cz,

C4, T4, T5, P3, P2, P4, T6, O1, O2 (Fig. 1). The Cz

(central part of the brain) is chosen as a reference.

When electrodes are installed on the subject head,

there will be a large impedance between the scalp and

the electrode. Therefore, electrolyte liquid is needed

which serves to minimize those impedance such that

the current (brain activity) flows more easily. The

used electrolyte liquid is electro-gel. Electrode

Figure 2: Position with impedance electrode.

EEG Patterns Analysis of Methadone Patients with Closed Eyes Condition using Wilcoxon Test

575

EEG Signal Record

Data Aquititions

Preprocessing

Feature Extraction

OUTPUT (frequency &

amplitude of the brain

activity)

impedance can be monitored in the WinEEG software

before the signal recording process is started. The

appearance of the impedance setting is shown in Fig.

2. The dark colour on the electrode indicator indicates

a large impedance (inactive), while the bright colour

indicates a low impedance. In this experiment, the

impedance is retained under 5 KOhm such that a

high-quality of the EEG data is obtained.

2.3 Pre Processing

The results of the recording of the EEG signal will be

obtained in the form of raw data which will be

followed by a filtering process using a Finite Impulse

Response (FIR) with a bandpass filter (0.5-70 Hz)

impulse response type and artifact removal using the

Independent Component Analysis (ICA) method

(Wang, 2014).

Independent Component Analysis (ICA) can be

used to extract the signal source underlying a series

of mixed signals being measured. In this study, the

ICA method was used to separate the EEG signal

from the overlapping artifacts on the electrodes

attached to the scalp assuming statistically the signal

source is independent.

EEG data is assumed to fit the following equation

model:

𝑥



𝑡



 𝐴𝑠



𝑡



𝑣𝑡 (1)

Where, in equation (1) there are three parts,

namely 𝑥,𝑠, and 𝑣, each of which is a vector of the

signal source, the observed signal, and the noise that

occurs at discrete time. 𝑥



𝑡







𝑥





𝑡



,𝑥





𝑡



,.…,𝑥





𝑡







is a linear mixture of

sources. 𝑁 𝑠



𝑡







𝑠





𝑡



,𝑠





𝑡



,.…,𝑠





𝑡







, 𝐴 is a

mixed matrix with size 𝑀𝑥𝑁, and 𝑣𝑡 

𝑣1𝑡, 𝑣2𝑡, … , 𝑣𝑀𝑡



is additional noise on the

EEG sensor.

2.4 Feature Extraction

To get the characteristics of each wave, feature

extraction will be carried out using the Fast Fourier

Transform (FFT). Mathematically represented by

equation (2), namely (Turnip, 2019):

𝑠



𝑓







𝑠



𝑡



𝑒



𝑑𝑡





(2)

Whereas 𝑠



𝑓



is the frequency domain signal,

𝑠



𝑡



is the time domain signal, and 𝑒



is a

constant.

The signal processing scheme is given in the

Figure. 3

Figure 3: Signal processing scheme.

2.5 Wilcoxon Signed-rank Test

The Wilcoxon signed-rank test is the nonparametric

test equivalent to the dependent t-test. As the

Wilcoxon signed-rank test does not assume normality

in the data, it can be used when this assumption has

been violated and the use of the dependent t-test is

inappropriate. It is used to compare two sets of scores

that come from the same participants. This can occur

when we wish to investigate any change in scores

from one time point to another, or when individuals

are subjected to more than one condition.

The Wilcoxon signed-rank test represented by

equation (3):

𝑊

∑

𝑠𝑔𝑛𝑥

,

𝑥

,

. 𝑅











(3)

Whereas 𝑊 is test statistic, 𝑁



is sample size, 𝑠𝑔𝑛

is sign function, 𝑥

,

,𝑥

,

is corresponding ranked

pairs from two distribution, and 𝑅



is rank i.

3 RESULT & ANALYSIS

The results of EEG recording on closed eyes can be

seen in Figure 2. Raw data in Figure 2 will go through

several stages of signal processing, namely from the

filtering process, removal of artifacts, feature

extraction, and up to data processing.

The effect of methadone use can be seen through

changes in the amplitude value before and after

CESIT 2020 - International Conference on Culture Heritage, Education, Sustainable Tourism, and Innovation Technologies

576

Figure 2: Raw data on closed eye.

consuming methadone. One way is to use the

Wilcoxon test. Wilcoxon test is intended for data that

are not normally distributed (Turnip, 2017). To

determine the influence of methadone use, it can be

seen from the Sig.2-tailed value. In this study, using

the assumption of accuracy with a Sig. 2-tailed value

<0.05 (p <0.05) which is equivalent to 95%. The

sig.2-tailed value can be seen from before 10 minutes,

before 1 hour after consuming methadone, and before

3 hours after consuming methadone.

Based on the results of recording with closed eyes,

it can be seen that each wave has a different rate of

change for each channel, as shown in Table 1.

Table 1: Recapitulation of the Wilcoxon test of 19 participants.

Channel

Delta Theta

lpha Gamma

Sig.2-

tailed

Number of

articipants

Sig.2-

tailed

Number of

articipants

Sig.2-

tailed

Number of

articipants

Sig.2-

tailed

Number of

articipants

- - - - - - 0.019 5

0.011 3 - - - - 0.003 5

0.033 4 - ---- -

0.02 4 - - - - 0.022 5

0.012 5 - ---- -

0.016 4 - - 0.049 12 0.036 5

0.009 3 - ---- -

0.049 5 - - - - 0.002 5

0.012 4 - - - - 0.046 7

0.022 4 - - 0.049 15 0.006 5

0.018 5 - - 0.005 15 0.018 6

0.018 5 - - - - 0.036 6

0.025 5 - - - - 0.03 6

0.013 3 - - - - 0.027 7

0.028 5 - - 0.012 14 - -

0.018 5 - - 0.03 14 0.014 6

0.012 5 - - - - 0.024 4

0.006 3 - ---- -

0.016 5 - - 0.027 14 0.014 6

Avera

e - 4.24 - - - 14 - 5.57

In Table 1, it can be seen that, in the delta, almost all

channels experienced significant changes with a p-

value <0.05, with the mean change of participants at

4.24 people. This change occurred before taking

methadone to 10 minutes after taking methadone. In

the theta wave, there was no significant change in all

channels and all recording stages. This is because all

of them have a p value> 0.05. In alpha waves, several

channels experience significant changes, namely on

the F4, Cz, C4, Pz, P4, and O2 channels with an

average number of participants who experience

changes, namely 14 people. However, not all of these

channels have undergone significant changes at the

same stage. Channels F4 and Cz occurred before

consuming methadone with 10 minutes after

consuming methadone, while C4, Pz, P4, and O2

occurred before consuming methadone 1 hour after

consuming methadone. This change in alpha waves

occurs, because of the p-value <0.05. In gamma

waves, almost all channels experienced significant

changes and occurred at the same stage, namely

before consuming methadone with 3 hours after

consuming methadone with the average participant

who experienced changes, namely 5.57 people. When

compared with the average number of participants

who experienced changes from before to after

EEG Patterns Analysis of Methadone Patients with Closed Eyes Condition using Wilcoxon Test

577

consuming methadone, the effect of methadone was

mostly felt in alpha waves although not in all

channels.

4 CONCLUSIONS

Based on the average number of participants, it can

be seen that there is an effect of methadone that is

mostly felt by 14 participants on alpha waves.

Besides, each wave occurs at a different recording

stage.

ACKNOWLEDGEMENTS

This research was supported by Technical

Implementation Unit for Instrumentation

Development (Deputy for Scientific Services),

Indonesian Institute of Sciences, Indonesia and

INSINAS 2019 Program from Ministry of Research,

Technology and Higher Education, Indonesia.

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