The Theta/Beta Ratio as an Indicator of Evolution in Pediatric

Patients Treated for Attention-Deficit/Hyperactivity Disorder

(ADHD)

A Retrospective Study

María Evangelina Herrán-Paz

, Raúl Ortiz-Monasterio

, Antonio Rodríguez-Díaz

, Olivia Mendoza

Juan R. Castro

and Hector J. Willys

Faculty of Chemistry Sciences and Engineering, Autonomous University of Baja, California, U.S.A.

Mexican Association of Neurology and Neurosurgery, Ave. Universidad, Tijuana, México

Keywords: Analysis EEG Signals, Theta/Beta Ratio, Clinical Evolution.

Abstract: This study was performed to assess whether the theta/beta ratio can be regarded as an indicator of pediatric

patients’ evolution while receiving treatment for ADHD. This required a spectral analysis of the

electrophysiological power output from several channels with reference at the vertex (Cz). The files and

EEG signals of sixteen clinical cases, which included children and adolescents from 4 to 16 years of age,

were analyzed. The analysis of the EEG signals was performed using the Fast Fourier Transform (FFT) to

obtain the frequency bands. Patients were under pharmacological treatment for at least one year and had at

least 2 EEG studies. The results indicate that a good correlation exists between the theta/beta ratio and the

patient’s clinical evolution. 42% of the patients who had 3 or more EEG’s, showed good correlation (r >

0.9), which was coherent with their good clinical evolution. 33% showed linear tendency (0.63 < r < 0.73),

with variable response and recovery tendency. 25% had bad correlation (r < 0.3), also with variable

treatment response. These results relate to poor adherence to the pharmacological treatment.

1 INTRODUCTION

The attention-deficit/hyperactivity disorder (ADHD)

is recognized as the main behavioral disorder of

children and adolescents, with 2.4 to 19.8%

worldwide prevalence (Polanczyk et al., 2007). This

neurobehavioral disorder is characterized by a

difficulty in focusing and maintaining attention for a

long time, plus impulsivity and hyperactivity (Ruiz

and Sauceda, 2012).

The clinical diagnosis of ADHD is complicated

due to many factors, like the difficulty in assessing

objectively the degree of attention, hyperactivity

and impulsivity, based on subjective information

provided by informants. The presence of other

neurological diseases and other clinical problems

related to attention deficit are other main difficulties.

The National Initiative for Children’s Healthcare

Quality (NICHQ) Vanderbilt rating scale is useful

for detection of ADHD in children and adolescents,

and includes the assessment of comorbilities, such as

oppositional defiant disorder, anxiety and

depression(Wolraich et al., 2012)(Wolraich et al.,

2003)(Becker et al., 2012).

Monastra et. al (Monastra, 2008), found that a

substantial body of scientific support exists that

associates ADHD with two primary

neurophysiological changes: most patients showed

excessive power in theta frequencies and suppressed

beta power over frontal and central midline regions.

A minority of them exhibited hyperarousal or no

evidence of cortical slowing over these regions.

Meta-analysis of the sensitivity and specificity of the

theta/beta power ratio to differentiate patients with

ADHD from healthy peers has indicated an accuracy

level comparable with or exceeding that of

commonly used behavioral rating scales.

The usefulness of the theta/beta ratio, which is

increased in comparisons to controls with no

neurological disorder, has been proved by several

authors (Monastra, 2008) (Steven Snyder et al.,

2008). The increased theta relative power and

277

Evangelina Herrán-Paz M., Ortiz-Monasterio R., Rodríguez-Díaz A., Mendoza O., R. Castro J. and J. Willys H..

The Theta/Beta Ratio as an Indicator of Evolution in Pediatric Patients Treated for Attention-Deﬁcit/Hyperactivity Disorder (ADHD) - A Retrospective

Study.

DOI: 10.5220/0005268502770282

In Proceedings of the International Conference on Bio-inspired Systems and Signal Processing (BIOSIGNALS-2015), pages 277-282

ISBN: 978-989-758-069-7

 2015 SCITEPRESS (Science and Technology Publications, Lda.)

theta/beta ratio and decreased beta relative power are

consistent with a meta-analytic review (Steven

Snyder and Hall, 2006). In a prospective study

(Quintana et al., 2007), rating scales readily

classified inattentive, impulsive, and/or hyperactive

symptoms as being due to ADHD, whereas only

EEG was specific. The use of theta and beta power

has produced more sensitivity and specificity in the

detection of ADHD in a diverse clinical sample,

rating scales and EEG were both sensitive markers.

EEG sensitivity of 94% and specificity of 100%,

was obtained whereas for ADHD-IV ratings scale

sensitivity of 80% and specificity of 22% was

obtained. Based on these statements, the quantitative

analysis of EEG (QEEG) is recommended to support

the diagnosis of ADHD, in wich the theta/beta ratio

is relevant.

Pharmacological treatment of ADHD is

recommended in children and adolescents with this

characteristic behavior to prevent problems and

develop a proper conduct at home, school and with

peers. There are a variety of drugs that help to

improve the patient’s school performance, personal

interactions, life quality and self-esteem. The

treatment must be individualized and is important to

consider the possible occurrence of adverse drug

reactions to changes in therapy (Graham et al.,

2011). Better results have been shown when patients

receive both pharmacological and psychosocial

therapy (Fogelman and Kahan, 2007). Non

adherence to treatment is common in these patients,

so the clinical evolution may vary depending on

compliance or adherence to prescribed treatment.

Monitoring the therapeutic drug is important to

follow the progress of ADHD symptoms, showing

when the patient responds favorably to treatment

and detecting cases in which the pharmacotherapy is

not being effective, allowing to search causes or

change the treatment schedule. For this, ratings

scales and performance tests can be used

(Vaquerizo-Madrid, 2008)(Herrán Paz et al., 2014),

however, the same subjectivity is recognized, the

questionnaires NICHQ Vanderbilt for parents and

teachers, is useful for this purpose (Wolraich et al.,

2012)(Becker et al., 2012), but based on the findings

of Snyders et al. (Steven Snyder and Hall, 2006),

(Steven Snyder et al., 2008), the EEG analysis could

be useful for therapeutic monitoring of the patient

clinical evolution.

Considering that ADHD has a characteristic

pattern useful for its diagnosis, this retrospective

study was performed in order to assess whether the

theta/beta ratio can be regarded as an indicator of the

evolution of pediatric patients receiving treatment

for this neurobehavioral disorder.

2 METHODS

2.1 Patients Files

This is a retrospective, non-randomized study.

Clinical files of sixteen ADHD pediatric and

adolescent patients were screened. There were 12

male and 4 female with mean age of 9.33  3.4 years

(range 4 - 16 years). The weight mean was 49 

23.78 kg (21.61 - 95.34 Kg) and the height mean

was 1.43  0.74 m (1.17 – 1.75 m). A specialist on

neurological disorders made ADHD diagnosis based

on DSM-IV clinical assessment, structured interview

and EEG. The NICHQ Vanderbilt ratings scale was

found in five cases and these results were also

considered to evaluate the presence and severity of

the symptoms of ADHD. Patients with ADHD

diagnosis, comorbilities (like oppositional defiant

disorder or conduct disorder, anxiety and

depression) and that were under pharmacological

treatment were included.

The analysis of EEG

signals of children and adolescents with ADHD

diagnosis, who received pharmacological treatment

for at least one year and have at least 2 EEG studies

(67 studies considered in total), is presented.

Exclusion criteria included a history of seizure,

schizophrenia, bipolar disorder, dissocial disorder

and known serious medical problems, metal plate or

metal device in the head.

EEG studies were performed according to

International 10-20 System with at least 1 year apart.

The analysis of the EEG signals was performed

using Fast Fourier Transform (FFT) to obtain

frequency bands: delta (0.5–3.5 Hz), theta (4.0–7.5

Hz), alpha (8.0–12.5 Hz), beta (13.0– 31 Hz) and

sub-divisions: delta 1 (0.5–1.5 Hz), delta 2 (2 – 3.5),

and beta 1 (13.0– 20.5 Hz) y beta 2 (21 – 31.5), the

periodogram and the power ratio of theta/beta bands.

Patient outcome was assessed based on medical

records, remission reports from NICHQ Vanderbilt

ratings scale and analysis of EEG signals (2 to 6

EEG’s per patient).

2.2 EEG

EEG studies were obtained using a digital device for

brain electrical activity mapping, Cadwell 32 ch.

EEG Amplifier, EASY II v. 2.1. The person

responsible for placing the electrodes and obtain

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records of EEG’s has training and experience in

such procedures. Electrodes were placed in

accordance with the International 10-20 System,

using a 19 electrode cap, with a ground electrode at

Fz and linked ears (A1 ad A2) reference. The

impedance is ≤ 10 KΩ

EEG’s were obtained with subjects lying down

and sleeping after a sleepless night. Specifications

for digitizing signals include a sampling frequency

of 200 Hz a notch filter at 60 Hz and a pass band 3

dB from 0.5 to 31.5 Hz 50 Hz Interference

suppression: 3 dB. The channels selected for data

analysis, are located in fronto-temporal sites, these

regions are related with the ADHD behavioral

problems.

2.3 Data Processing

Data processing was made on certain steps:

1. Segment elimination based on presence of

artifacts, this procedure was made visually.

2. Data filtering, a pass windows of 0.5-31.5Hz

and a notch filter at 60Hz were used.

3. The following frontal and temporal channels

were used: FP1, FP2, F3, F4, F7, F8, T3, T4,

T5, T6 and Fz. Power spectrum (based on Fast

Fourier Transform) was obtained for the whole

EEG record.

4. Calculate power bands: delta (0.5-3.5Hz) theta

(4-7.5Hz) alpha (8-12.5Hz) and beta (13-

31.5Hz).

5. Get ratio Theta/beta.

2.4 Statistical Analyses

We hypothesized that clinic evolution of pediatric

ADHD patients under pharmacologic treatment

would follow changes in the theta/beta ratio through

time.

Theta/beta ratio has been recognized as a

characteristic pattern of this neurobiological disease,

we think that patients under treatment will improve

health, and theta/beta ratio will decrease

significantly. A paired T-test was used to compare

the initial and final theta/beta ratios at 95%

confidence interval. A good linear correlation

between theta/beta ratio versus time under treatment

will show a good clinical evolution and good

adherence to the treatment. A linear tendency will

show a variable response with improvement

tendency. A bad linear correlation will be associated

with a variable response and slight improvement or

without clinical improvement.

3 RESULTS

3.1 Physical Characteristics

Medical files of sixteen child and adolescent ADHD

patients were studied retrospectively. They where 12

male and 4 female with mean age of 9.33  3.4

years. Four cases had two EEG studies and twelve

had three to 6 EEG’s. The patients were taking

stimulants like methylphenidate, and other drugs

like: magnesium valproate, lamotrigine, risperidone,

and others for comorbilities treatment.

3.2 EEG

Table 1, shows the theta/beta ratio for the 16 cases,

for each electroencephalographic study. Theta/beta

ratio decreased in most cases (87.5%, n=14), one

case (6.25%) without changes and other case had an

increment of the theta/beta ratio. The Theta/beta

ratio decrease was related to a good clinical

evolution. Initial and final EEG studies were

compared for each case using a paired T-test, a

significative difference was found at 95%

confidence interval.

Table 2 shows correlation coefficients obtained

from patients with 3 or more EEG’s (12) and this

was related with the clinical evolution, considering

retrospective analysis of clinical histories.

Considering only 12 such cases, 41.66% of this

patients (5) had a good clinical evolution, this is

coherent with a good linear correlation between

theta/beta ratio versus time under treatment,

correlation coefficients (r) were 0.977  0.015,

range: 0.991 to 0.951.

Four cases (33.33%) shown a linear tendency,

their mean correlation coefficient was r=0.666  0.

045, varied from 0.731 to 0.627.

Three cases (25%) shown a very low correlation

coefficients r, with mean of 0.206  0.156, range

varied from 0.310 to 0.026.

These coefficients were associated with a good,

variable or bad clinical response, characterized by

periods with variable adherence and periods of

discontinuing the therapy.

For cases with only two EEG (n=4), clinical

evolution was assessed according to medical

records, three of them had a good evolution and one

case was bad.

TheTheta/BetaRatioasanIndicatorofEvolutioninPediatricPatientsTreatedforAttention-Deficit/HyperactivityDisorder

(ADHD)-ARetrospectiveStudy

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Table 2: Linear correlation coefficients of the

theta/beta ratio.

Linearity % Mean

(SD)

Good

(n=5)

R > -0.95 41.67 -0.997

(0.015)

With

Tendency

(n=4)

-0.73 > R > -0.63 33.33 -0.666

(0.045)

Low

(n=3)

-0.03 > R < 0.31 25.00 -0.206

(0.156)

SD: Standard deviation

4 DISCUSSION

Patients were taking pharmacological treatment and

most of them had frequent periods of nonadherence

to pharmacotherapy, with periods of improvement

and relapse associated with such phenomenon.

Five patients had NICHQ Vanderbilt

questionnaire, these rating scales were assessed by a

psychologist. The information obtained from these

rating scales answered by parents and/or teachers

was included in Table 1, and was considered for

assessment of patient’s clinical evolution. In all

these cases (n=5), results were: “in remission” or

“without ADHD symptoms”.

Table 1: Relation theta/beta and patient’s clinical evolution.

case

Theta/beta ratio

each year of treatment, mean (SD)

R Clinical

Evolution

10.58

(3.58)

4.54

(1.87)

5.71

(1.73)

5.55

(2.16)

N.D.

3.70

(1.87)

-0.731

Variable

Remission

5.85

(2.34)

4.49

(1.44)

N.D.

3.45

(0.85)

N.D. N.D.

2.95

(1.00)

2.02

(0.25)

-0.952

Good

10.03

(3.09)

6.39

(1.88)

4.18

(1.82)

2.70

(0.67)

-0.98

Good

Remission

11.77

(4.12)

10.59

(5.05)

9.94

(4.80)

-0.985

Good

Remission

8.59

(2.93)

N.D.

8.19

(2.75)

N.D. N.D. N.D. N.D. N.D.

5.13

(1.71)

-0.991 Good

2.63

(1.00)

N.D. N.D.

2.43

(0.58)

Good

4.24

(1.55)

4.67

(1.32)

Bad

7.22

(2.31)

5.61

(1.73)

N.D.

2.30

(1.42)

4.94

(1.60)

4.88

(0.87)

-0.628

Variable

7.06

(3.83)

14.14

(5.43)

9.54

(3.56)

4.40

(1.55)

6.11

(2.41)

3.32

(1.09)

-0.651

Variable

Remission

3.29

(0.90)

2.40

(0.61)

Good

4.29

(1.33)

5.98

(1.74)

3.63

(1.35)

3.43

(0.87)

0.281

Variable

SPI

21.42

(8.31)

16.96

(6.12)

6.92

(5.04)

-0.976

Good

Remission

8.18

(2.75)

5.12

(2.03)

7.22

(2.18)

N.D.

6.04

(1.80)

4.65

(3.07)

-0.654

Variable

9.11

(3.62)

6.61

(2.98)

10.50

(4.18)

9.11

(3.20)

0.31

Variable

Bad

3.91

(1.71)

0.89

(0.30)

Good

3.59

(1.69)

N.D. N.D.

6.81

(2.19)

4.28

(1.29)

3.38

(0.85)

-0.026

Variable

SD: Standard deviation, R: Correlation coefficient, PI: Patient Improvement , SPI: Slight patient improvement.

N.D.:No data available

BIOSIGNALS2015-InternationalConferenceonBio-inspiredSystemsandSignalProcessing

280

Theta/beta ratio decreased in most cases (87.5%,

n=14), one case (6.25%) without changes and other

case had an increment of theta/beta ratio.

50% of patients (n=8), had good clinical

evolution, 43.75% had a variable response and

12.5% had bad clinical response. Poor adherence to

treatment was associated with variablity in theta/beta

ratios and in their response to pharmacological

therapy. Pharmacological treatment with this sample

was varied and interrupted in several occasions and

resumed after patients worsening.

The main problem related with pharmacotherapy

in these patients was low adherence at the treatment.

100% of cases discontinued treatment for weeks or

even months at least once. When this happened, a

new EEG was obtained and the patient reinitiated

treatment. Then the EEG’s changes are not related

directly with the time of treatment. Studies of

pharmacy claims databases and treatment studies

have shown that the prevalence of medication

discontinuation or nonadherence is between 13.2%

to 64% and medication nonadherence is common in

childhood/adolescent ADHD (Adler and Nierenberg,

2010).

Previous studies had found that a minor

percentage of children diagnosed with ADHD, may

show excessive beta activity in their resting state

EEG, generally associated with a negative response

to methylphenidates and dexamphetamines (Clarke,

et al., 2001), however this pattern was not present in

these study cases. In other study(Steven Snyder et

al., 2008), the theta/beta ratio was obtained in order

to identify ADHD patients in three age groups: 6-11,

12-15 y 16-18 years. The EEG was obtained in

resting state with close eyes. In comparison with our

results in patients under the same age group. The

theta/beta ratio in this studio was 7.4  3.3 and 4.1 

1.1 for the first and second group of age, while in

our study, the theta/beta ratio obtained before

treatment was: 7.12  3.1 for the patients who were

in the group of age of 6-11 years (n=12), the

theta/beta ratio obtained on patients after treatment

was 5.11  2.83 (n=9) and 3.14  1.16 (n=5) for the

first and second group of age respectively.

Figure 1 show the patients’ clinical evolution,

classified as: Good, variable with patient

improvement, variable with slight patient

improvement and bad, corresponding to sixteen

cases studied. In order to relate this observations

with the theta/beta correlations obtained in twelve

of sixteen cases, we grouped the last two categories

in only one (variable with slight patient

improvement and bad).

Fig. 1: Patients’ clinical evolution, according medical

valoration.

There is some future work pending for other

studies, an example could be a study in which EEG

signals from a given sample are taken under

different states as resting state with closed eyes and

sleeping state and compare results. Another example

of future work could be the automate of the process

of EEG data analysis in a system such that the

theta/beta ratio could be given to the doctor in

minutes and this information could be used to help

ADHD diagnosis.

4.5 Limitations

First, a small sample was examined in this study, a

study with a larger sample size will be required.

Second, a single psychiatric clinical site for the

current study which limits the generalizability of the

results.

Third, we focused in theta/beta ratio but other

patterns may be useful to evaluate patient evolution.

5 CONCLUSIONS

Theta/beta ratio obtained from EEG signal analysis

can be an indicator of clinical evolution of ADHD

patients. The main factor for variability in response

to changes in theta/beta ratio is a reflect of

nonadherence to pharmacotherapy, with associated

periods of improvement and relapse.

ACKNOWLEDGMENT

This study was supported by National Council for

Science and Technology of México

(Conacyt).Project 209537.

TheTheta/BetaRatioasanIndicatorofEvolutioninPediatricPatientsTreatedforAttention-Deficit/HyperactivityDisorder

(ADHD)-ARetrospectiveStudy

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