Methadone Effects on Frontal Brain Lobe based EEG-P300 Waves in

Drug Rehabilitation Patients

Arjon Turnip

, M. Agung Suhendra

, Dwi Esti Kusumandari

, Faza Lisan Sadida

, Simon Willy

Laufried

, Siti Aminah Sobana

, Arifah Nur Istiqomah

and Daniel Sutopo Pamungkas

Instrumentation Development, Indonesian Institute of Sciences, Jakarta, Indonesia

Faculty of Medicine, Padjadjaran University, Bandung, Indonesia

Electical Engineering, Politeknik Negeri Batam, Batam, Indonesia

Keywords: EEG-P300, Methadone, Visual Stimuli, Frontal Lobe

Abstract: Drug abuse in various parts of the world is increasingly widespread. Therefore, a drug addict should

immediately stop and must be recovered. To overcome the symptoms of addiction, the use of methadone as a

synthetic drug to replace opioid type drugs is recommended. In this paper, an experiment with rehabilitation

patients to identify the effect of the drugs on the brain activity in the frontal, central, temporal, and occipital

lobes is proposed. The EEG data collection is performed using 18 channel electrodes, namely central: C3, C4;

frontal: Fp1, Fp2, F3, Fz, F4, F7, F8; occipital: P3, Pz, P4, O1, O2; and temporal: T3, T4, T5, T6. In the brain

signals record, subjects were asked to comfortably sit in a chair. The recording was done in three sessions: 5

minutes before drinking methadone, 10 and 60 minutes after drinking the methadone, respectively. To reduce

background noise and artefacts removal, band pass filter (0.5-50 Hz) and wavelet method were applied,

respectively. From this experiment it was found that a decrease in amplitude after methadone intake for

average in four lobes is obtained. This results indicates that the use of methadone is highly effect on the entire

brainwave activity which indicates a decrease in the level of desire to do activities.

1 INTRODUCTION

Drug abuse in various parts of the world is

increasingly widespread. Various cases show

material and non-material losses and even cause the

death. Therefore, a drug addict should immediately

stop and must be recovered. According to Indonesian

law, narcotics addicts and victims of narcotics abuse

must serve out medical rehabilitation and social

rehabilitation (Undang-Undang Republik Indonesia

No. 5 tentang Psikotropika, 1997). It regulates that

narcotics addicts and narcotics abuse victims who are

undergoing the process of investigation, prosecution

and trial in court are supported with treatment and

recovery in rehabilitation institutions (BNN

Regulation 11/2014) (Badan Nasional Narkotika,

2007). By law, the state is responsible for recovering

drug users through rehabilitation. Therefore, there

should be no obstacles for rehabilitation programs,

including regarding infrastructure or facilities for the

recovery of drug addicts. Drug rehabilitation consists

of three stages namely medical rehabilitation

(detoxification), social or non-medical rehabilitation,

and advanced development. Some detoxification

techniques include cold turkey method where the

patient is locked up in the addiction (sakau) phase,

substitution or replacement therapy where the needs

of opioid or heroin addicts are replaced with other

types of drugs such as methadone, or symptomatic

therapy where drug administration is adjusted to the

user's complaints.

The therapeutic method with an effective medical

approach that still recognized today is a drug

switching program to another substance called

methadone therapy (Wang, Kydd, Wouldes, Jensen,

& Russell, 2015; Yang, et al., 2015; Turnip, et al.,

2018; Turnip, Kusumandari, Hidayat, 2018; Hu, et

al., 2017). There are a variety of positive benefits that

allow patients to be able to carry out their normal

activities, but methadone therapy also causes side

effects and the dependence that can psychologically

affect the patients’ quality of life (Yang, et al., 2015;

Maeyer, et al., 2011; Lin, et al., 2016; Malik,

Adelson, Sason, Schreiber, Peles, 2019). Methadone

is a therapy used for drug addicts from opioid groups

Turnip, A., Suhendra, M., Kusumandari, D., Sadida, F., Laufried, S., Sobana, S., Istiqomah, A. and Pamungkas, D.

Methadone Effects on Frontal Brain Lobe based EEG-P300 Waves in Drug Rehabilitation Patients.

DOI: 10.5220/0010350600050011

In Proceedings of the 3rd International Conference on Applied Engineering (ICAE 2020), pages 5-11

ISBN: 978-989-758-520-3

such as heroin, morphine and codeine including

methamphetamine. The methadone therapy must be

routinely done. Methadone is a group of opiate

analgesics that can be used to treat ongoing severe

pain (such as pain due to the cancer). This substance

works directly in the brain by changing how the body

feels and how the body responds to the pain.

Methadone is also used to treat dependence on

narcotic drugs (such as heroin) as an approved

therapy program. It can also help prevent withdrawal

symptoms due to the drug withdrawal (Hu, et al.,

2017; Wang, Kydd, Wouldes, Jensen, & Russell,

2015; Yang, et al., 2015; Malik, Adelson, Sason,

Schreiber, Peles, 2019). The success of substitution

therapy such as the methadone program for drug

addicts is higher than rehabilitation without drugs or

detoxification. Even with this therapy, the spread of

HIV can be suppressed because the use is done by

drinking. Some researchers have found that

methadone maintenance can significantly reduce

craving symptoms except in patients with heroin

dependence. Long-term consumption of heroin

causes adaptive changes in the brain system that may

last for a long time (Li, 2012). Verdejo, et al. (2005)

has found that methadone itself has the side effect of

causing cognitive impairment. Other researchers have

found that rehabilitation can effectively repair

impaired cognitive function caused by

buprenorphine, placebo, and methadone (Attou,

Figiel, Timsit-Berthier, 2001).

Electroencephalogram (EEG) is an activity that

records spontaneous brain activity in the form of

potential electrical signals along the scalp produced

by interconnected neurons. Among the medical use of

EEG, among others, for the diagnosis of diseases

associated with brain and psychiatric disorders

(Pastor, et al., 2019; Wang, Kydd, Wouldes, Jensen,

& Russell, 2015; Turnip, et al., 2018; Hu, et al.,

2017). EEG is also applied to detect a person's mind

patterns or mental condition. Visual observation of

the EEG signal directly is very difficult given the

amplitude of the EEG signal is so low and the pattern

is very complex. Besides that, EEG signals are

strongly influenced by various variables, including

mental condition, health, activity of the patient,

recording environment, electrical disturbances from

other organs, external stimulation, and age of the

patient. The nature of EEG signals in general is non

stationary and random so that adds complexity to the

processing of EEG signals (Turnip, et al., 2018; Hu,

et al., 2017; Iskandar, Kusumandari, Turnip, 2019;

Turnip, Kusumandari, Pamungkas, 2018). However,

the classification of EEG signals to changes in certain

variables can explain the work function of the brain

and capture changes in brain activity to the relevant

variable.

EEG signal in a person, generally consists of wave

components which are distinguished based on their

frequency region, namely: Human brain waves have

a range of frequencies and amplitudes - different so

that it is divided into several types of waves, namely:

delta waves (when deep asleep and without dreaming)

have the frequency is less than 4 Hz with an amplitude

of about 10 μV. Theta waves (occurring when light

sleep or drowsiness) have frequencies between 4 –8

Hz with an amplitude of around 10 μV; Alpha waves

(occur when relaxation or transition between

conscious and unconscious states) have a frequency

between 8-13 Hz with an amplitude of around 50 μV.

Beta waves (in a state of thinking or in the activity)

have a frequency between 13-19 Hz with an

amplitude between 10-20 µV. Gamma waves

(experiencing very high mental activity such as fear,

very panic, appearing in public) have a frequency

between 19-100 Hz (Motlagh, et al., 2018; Zhang, et

al., 2017). Therefore, the representation of EEG

signals into the frequency domain is mostly done in

research related to EEG signal analysis. In this study,

the use of EEG signals to observe the effect of

methadone administration on changes in brain

activity in the central, frontal, parietal, occipital, and

temporal parts is proposed. So far, methadone

experiments and observations of their effects on brain

activity using brain waves from EEG signals are still

rarely done.

2 METHODS

Experiments were carried out in a room that was

conditioned away from noise and provided comfort

for the subject (Figure 1). Before conducting an EEG

signal recording session, the subjects first directed

interviews with the medical team, filled out

information of concern, and follow the urine tests.

Then the subject is attached to an instrument in the

form of an electro-cap on the head and also tied a belt

to the chest of the subject so that the electro-cap does

not shift. Subjects were briefed regarding the

experimental scenario. The EEG signals are recorded

through 19 channel electrodes, including Fp1, Fp2,

F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz,

P4, T6, O1, and O2. The reference in this experiment

uses electrodes mounted on the ear, the A1 and A2

channel electrodes, which are A1 for the left ear and

A2 for the right ear. When installing electrodes, a gel

is applied to each EEG sensor to increase

conductivity while maintaining impedance between

ICAE 2020 - The International Conference on Applied Engineering

the scalp and electrodes below 5 k. The electrode

mounting position, the electrolyte liquid used in the

form of an electro gel, and the impedance shown in

Figure 2. The electrode impedance can be monitored

in WinEEG software before the signal recording

process is started. The dark color on the electrode

indicator indicates a higher impedance, while the

bright color indicates a low impedance level.

In addition to fix the electrode impedance, another

thing to consider is setting the recording process in

the WinEEG system. Settings include the sampling

frequency used which is 500 Hz, the list of channels

to be used and their references, and interconnection

with PCs / laptops to display the stimuli used when

recording EEG signals. During the recording process,

subject was asked to sit relaxed while closing his

eyes. Experimental time allocated for each trial is 1

hour and 10 minutes. The time is divided into 3

sessions, namely 5 minutes before, 10 minutes after,

and 60 minutes after consuming methadone. After the

recording session is finished, the recording of the

EEG signal is exported into a file with EEG format,

which the file can later be processed using a signal

processor.

Figure 1: The experiment design.

Figure 2: (a) Electrode position, (b) electrogel for

conductivity, (c) electrode conductivity with around 5 k



impedance.

3 SIGNAL PROCESSING

EEG raw data is processed with C2 references using

18 channels from 8 subjects. The 18 channels that are

used are grouped according to the brain lobes, namely

Central: C3, C4; Frontal: Fp1, Fp2, F3, F2, F4, F7,

F8; Parietal Occipital: P3, Pz, P4, O1, O2; Temporal:

T3, T4, T5, T6. The average amplitude (after

extraction) of each channel group is calculated.

Before the data is processed montage reference is

changed to the middle part of the brain with the Cz

channel. Recording of each subject is done for ± 5

minutes per session. Data is taken from 10 seconds to

130 seconds because data processing will be more

effective if taken 2 minutes of data that is clean and

free of artefacts. Data recording before the 10th

second is cut because the initial 10 seconds are

considered to be still corrupted by noise where the

subject is still adjusting to the experimental

conditions.

From Figure 3 raw data generated, clearly visible

on the EEG signal there are still many artifacts which

make it difficult in understanding the character of the

signal, therefore the next processes are needed.

Methadone Effects on Frontal Brain Lobe based EEG-P300 Waves in Drug Rehabilitation Patients

(A)

(B)

Figure 3: Raw data of EEG in relax and close aye condition:

before and (b) after Methadone intake.

To reduce background noise, the filtering process

for EEG raw data is carried out. Bandpass filter is a

circuit that is designed to pass the frequency within

certain limits and reject other frequencies outside the

desired frequency. And bandpass filter is a

combination of highpass and lowpass filter. In the

experiment, the cut off frequency used is 0.5 and 50

Hz. As for feature extraction, the wavelet method

with the symlet model and the 5 level decomposition

process is used.

Wavelet transform is a signal processing method

by resembling signal analysis using Fourier

transforms, namely by breaking the signal to be

analyzed into several parts. The difference, if the

Fourier transform signal is broken down into signal

sinusioda with different frequencies, then the wavelet

transformation of the analyzed signal is broken down

into a number of signals resulting from shifting and

scaling of a small signal called a wavelet. The wavelet

transform method in Equation (1) (Jawabri &

Sharma, 2019), mainly used to identify true

components and remove noise from the raw data

(

)







(

)



)

with

(1)

where,



j,k

(t)  2







t  k , where



(t) is the

mother wavelet, f (t) is the series analyzed, and t

indicates the time; integer j indicates the

decomposition level, and k indicates the time

translation factor, and



*(t) is the complex

conjugate.

The first step of the wavelet application starts

from the original signal then the coefficients set is

approximated on each level. In each step except the

first one, only the approximated coefficients are

analyzed. The wavelet used must meet the regularity

of order N condition in Eq. (2)







(

)







1 (2)

Under the level of j, the original signals can be

reconstructed using Eq. (3).

(

)





(

)



*(2



)

(3)

By increasing the decomposition level j, the

detailed information of signals at larger temporal

scales would obtained. The more contribute

information we have, the better performance of the

model is achieved. However, more input could reduce

the computing efficiency and decrease the stability of

the model. Therefore, it is important to select an

appropriate decomposition level for wavelet

modeling.

4 RESULTS AND DISCUSSION

Drugs provide a dominant effect on the functioning

of the four brain lobe: frontal, parietal, temporal, and

occipital lobes. These effects can be observed if brain

activities is record and processed. In the experiment

of brain activity record, a group of subject is asked to

sit in relax while closing their eyes. The brain wave is

recorded about three times: before, 10 minutes, and

60 minutes after taking methadone. Assumption that

subjects who are follow the rules of experiment will

fill craving in the first record, starts to comfort after

10 minutes, and feel comforts after 60 minutes of

consuming methadone. The differences in the

amplitude of the extracted EEG before and 1 hour

after the subject consume the methadone in four

region of brain is observed. Subjects who have not

been given methadone have a higher level of interest

in methadone (craving), consequently the amplitude

after consuming methadone must be lower. The

decrease in amplitude value is also supported by the

influence of methadone which tends to make the

subject sleepy where theta waves increase and beta

waves decrease.

The cerebral cortex of the brain can be divided

into four lobes (see Figure 4): The frontal, parietal,

occipital, and temporal lobes. They are associated

with different functions into the body ranging from

reasoning to auditory perception. The frontal lobe is

associated with motivation, thinking, movements,

cognition, and expressive language. Damage to the

frontal lobe can lead to changes in sexual habits,

socialization, and attention as well as increased risk-

taking. The parietal lobe is associated with processing

ICAE 2020 - The International Conference on Applied Engineering

tactile sensory information such as pressure, touch,

and pain. The temporal lobe is important for

interpreting sounds and the language. Damage to the

temporal lobe can lead to problems with memory,

speech perception, and language skills. The occipital

lobe is associated with interpreting visual stimuli and

information. Damage to this lobe can cause visual

problems such as difficulty recognizing objects, an

inability to identify colors, and trouble recognizing

words (Jawabri & Sharma, 2019).

Because drugs affect the work of brain, drugs can

change the mood of feelings, ways of thinking,

awareness, and behavior of the wearer. That is why

narcotics are called psychoactive substances. There

are several kinds of effects of drugs on the brain, such

as inhibiting the work of brain, called depression.

This state could reduce awareness resulting in

drowsiness. Drugs can also stimulate the work of the

brain or what is often called a stimulant, so that arises

a sense of freshness and enthusiasm, increased

confidence, and relationships with others become

close. However, this can cause inability to sleep,

restlessness, faster heart palpitations, and increased

blood pressure. Some drugs could cause delusions, or

what are often called hallucinogens. Narcotics abuse

has an influence on the work of the nervous system,

including: Sensory nerve disorders (central and

occipital lobes) that cause numbness and blurred

vision that can cause blindness; Autonomic nerve

disorders (frontal lobe) that cause unwanted

movements through motor motion. Impaired motor

nerves (central and frontal lobes) that cause loss of

coordination with the motor system. Vegetative nerve

disorders (frontal, temporal, and central lobes) cause

language to come out of consciousness and cause fear

and lack of confidence.

Figure 4: Brain lobe effected by Methadone.

Table 1 shows the mean amplitude of each lobe

before and after consuming Methadone. The results

of previous studies show that drug use automatically

affect brain performance in each lobe such as

disturbing vision for the occipital, movement, and

language for central and frontal, emotions for

temporal. In theory, if someone who is craving is

given Methadone then the subject should feel more

comfortable after an hour. Based on the experimental

results in Table 1, except for subjects 5 and 6, the

average amplitude in each lobe has decreased.

Individually, subjects 2, 3, 4, 7, and 8 have their

respective amplitudes increasing at central, occipital,

frontal & temporal, occipital, central, and frontal

parts.

When compared with subjects 5 and 6, the

increase is not that significant. Subjects 5 and 6 had

lobes of increased amplitude after taking Methadone.

Based on the history of substance use, the two

subjects used almost the same drugs and the most

compared to other subjects. Both have almost the

same age with few mental disorders and a relatively

high value of impulsivity. They also took high doses

of Methadone even though they had been undergoing

rehabilitation for a long time (subject 5 had rehab for

11 years). Subjects 5 and 6 also consumed

benzodiazepines during the experiment.

Based on the demographic conditions of two

subjects, it can be understood that the increase in the

amplitude value of brain activity in each lobe is the

result of impaired brain function in the related area.

The highest increase was seen in subject, 6 which is

about 6.5 times the time of craving. Meanwhile, the

increase in subject 5 is only about 2.5 times from the

condition at craving. Based on demographic

conditions, subject 6 still consumed very high doses

of methadone or the maximum dose during the

experiment. It is suspected that subject 6 does not

follow routine and adequate rehabilitation.

Meanwhile, subject 5 had obtained a significant

reduction in dose to the maximum dose. However,

because the age of using the drug is quite long, which

is 11 years, it is likely that a lot of brain nerve tissue

has been damaged so that even though it has been

given Methadone, brain function cannot return to

normal.

Subjects 4 and 8 both had two lobes in which the

amplitude of brain activity did not decrease. Both

subjects had the second-highest history of substance

use than other subjects, and the dose was almost the

same as the maximum dose. When viewed as a whole,

changes in the brain activity amplitude after

consuming Methadone are closely related to history

of substance use and decreased Methadone dose.



Methadone Effects on Frontal Brain Lobe based EEG-P300 Waves in Drug Rehabilitation Patients

When compared with subjects 2 and 3, subject 7

experienced a significant increase in the amplitude of

the occipital region, which is almost 4 times

compared to the craving condition. Based on the

results of urine tests, subject 7 is suspected to

consume benzodiazepines and methamine during the

experiment. These conditions sufficiently state the

reasons for the increase in the associated amplitude.

Table 1: Amplitude of brain activity in the lobe of central,

frontal, occipital, and temporal: before, 10 minutes, one

hours of methadone intake.

Amplitude

Lobes Before 10 m 1 hours

Central

28.29 20.82 10.01

Frontal

119.80 63.73 8.34

Ocipital

48.23 37.78 15.40

Temporal

69.81 63.78 20.52

Central

7.80 5.82 18.12

Frontal

10.08 12.06 9.10

Ocipital

9.85 14.40 3.27

Temporal

10.55 17.04 2.71

Central

216.88 131.25 55.29

Frontal

84.02 61.15 33.26

Ocipital

89.55 105.08 124.45

Temporal

36.77 31.04 11.39

Central

42.69 28.47 32.42

Frontal

26.47 28.07 29.34

Ocipital

34.85 17.94 32.73

Temporal

8.70 8.46 9.34

Central

14.46 28.87 49.23

Frontal

15.17 21.83 50.79

Ocipital

20.55 59.43 25.65

Temporal

4.58 7.32 18.28

Central

24.49 20.47 120.79

Frontal

24.50 22.86 122.04

Ocipital

13.93 22.32 197.58

Temporal

16.74 5.6 92.36

Central

40.58 11.69 5.498

Frontal

38.51 11.85 8.81

Ocipital

1.25 6.76 5.46

Temporal

16.65 3.37 3.49

Central

27.05 28.41 33.38

Frontal

23.26 23.49 31.73

Ocipital

16.40 14.85 16.89

Temporal

7.93 9.83 7.53

5 CONCLUSIONS

Methadone intake by the drug rehabilitation patients

causes a decrease in the brain's impulsivity to given

stimuli, which indicates a decrease in the level of

desire for drugs after being given Methadone. The

main results of present analysis indicated that the

subjects have a longer P300 latency and a lower P300

amplitude after consuming Methadone. This study

revealed that drug patients have abnormalities in the

P300 component, which may reflect deficits in

cognitive function.

ACKNOWLEDGEMENTS

This research was supported by Technical

Implementation Unit for Instrumentation

Development, Indonesian Institute of Sciences and

funded by RISTEKDIKTI by INSINAS 2019,

Indonesia.

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Methadone Effects on Frontal Brain Lobe based EEG-P300 Waves in Drug Rehabilitation Patients