國立交通大學光電工程研究所

National Chiao Tung University

以功能性近紅外光光譜術進行大腦量測:
偏頭痛檢測與注意力不足過動症治療之研究

Migraine Detection and ADHD Neurofeedback Treatment

based on fNIRS measurements

Student: Wei-Chih Tang

Advisor: Prof. Chia-Wei Sun

台北榮民總醫院
神經醫學中心一般神經科
 01 Near-infrared spectroscopy (NIRS)

02 Migraine detection

03 Attention deficit hyperactivity disorder treatment

04 Conclusion & Future works

1
 Near-infrared spectroscopy (NIRS)

2
01
Modified Beer-Lambert Law
700nm 900nm

V. Vinoth Kumar, et al.Published in Asian journal of psychiatry 2017

3
01
Modified Beer-Lambert Law
700nm 900nm Isosbestic 1 800 nm
Multi-wavelength
point 2 800 nm

V. Vinoth Kumar, et al.Published in Asian journal of psychiatry 2017

3
01
Neurovascular coupling

HbO2: oxyhemoglobin
HHb: deoxyhemoglobin
4
01
Neurovascular coupling

CBF: cerebral blood flow

CBV: cerebral blood volume
4
01
NIRS
Advantages
Wearable
Low cost
Real time
User friendly
MRI High temporal resolution
High tolerance of movement
Clinical research
Advantages
User friendly
Children
High tolerance of movement Home Care
EEG
5
01
Wearable NIRS system setup

ch2 ch3
ch1 ch4

Left channel Right channel

6
 Migraine detection
01 Introduce to migraine

02 Experimental design

03 Classification algorithms

04 Results

7
 02
Introduction to migraine

Migraine is the rd most 3 Ages 25 ~ 45

prevalent illness in the world.

01 02 03 04

4-72
Recurrent Last for hours Nausea Sensitivity to
headache to days Vomiting light and sound

Bonafede M, Sapra S, Shah N, Tepper S, Cappell K, Desai P. Direct and indirect healthcare resource utilization and costs among
migraine patients in the United States [published online February 15, 2018].

8
02
Motivation
Healthcare
lost productivity $36 billion
The vast majority of migraine
sufferers do not seek medical NIRS
care for their pain.
Machine
More than half of all migraine
learning
sufferers are never diagnosed.
Assist migraine diagnosis
GoM, BilbaoA. Orbitofrontal dysfunction predicts poor prognosis in chronic migraine
with medication overuse. 2011:459-466. doi:10.1007/s10194-011-0340-6

9 https://migraineresearchfoundation.org/about-migraine/migraine-facts/
 02
Motivation Mental stress Pain perception

1 Mental arithmetic
orbitofrontal cortex Prefrontal cortex gray
hypo-metabolism matter decreased
2 Calf restraint
3 Concentration task
Rocca, Maria A., et al. "Brain gray matter changes in migraine patients with T2-
visible lesions: a 3-T MRI study." Stroke 37.7 (2006): 1765-1770.

10
02
Experimental design Mental arithmetic

(a)-(b)-(c)-(d)-(a)…

Rest 60 sec Task 315 sec Recovery 180 sec

11
02
Experimental design Calf restraint Numerical rating scale, NRS
Standard pain level

Left calf 10

6-8

Pre-test NRS Post-test NRS

Rest 60 sec Task 90 sec Recovery 75 sec

12
 02
Experimental design Concentration task

Baseline Regulatory trail Reinforcement

5 sec 30 sec 5 sec
Rest
20 sec
…… Repeat
6 times
NeuroscienceH, MarxA, EhlisA, et al. Near-infrared spectroscopy ( NIRS ) neurofeedback as a treatment
for children with attention deficit hyperactivity disorder (ADHD)— a pilot study. 2015;8(January):1-13.
13
 02
Experimental design Concentration task

(a) Baseline
(b) Regulatory trail
(c) Reinforcement
(d) Rest

Baseline Regulatory trail Reinforcement

5 sec 30 sec 5 sec
Rest
20 sec
…… Repeat
6 times
NeuroscienceH, MarxA, EhlisA, et al. Near-infrared spectroscopy ( NIRS ) neurofeedback as a treatment
for children with attention deficit hyperactivity disorder (ADHD)— a pilot study. 2015;8(January):1-13.
13
02
Experimental design Concentration task
(a) Baseline (b) Regulatory trail
Visual feedback
Airplane height
[HbO2]regulatory trail – mean of [HbO2]rest
(c) Reinforcement (d) Rest

> threshold 0.7, height++ Focus

duration
< threshold 0.7, height - -

Baseline Regulatory trail Reinforcement Rest

5 sec 30 sec 5 sec 20 sec
13
02
4-th order low pass filter
Classification algorithms cutoff frequency = 0.1Hz

2 3
1

Machine
Learning
SVM: Support Vector Machine
PCA: Principal Components Analysis
14
02
Classification algorithms
Support vector machine (SVM)

15
02
Classification algorithms
Support vector machine (SVM)

15
 02
Classification algorithms
Support vector machine (SVM)

mature technology
S, Shylaja & , Dr.R.Muralidharan. (2018). A novel method to Huang S, Cai N, Pacheco PP, Narrandes S, Wang Y, Xu W. Applications of Support Vector
predict heart disease using SVM algorithm. Machine (SVM) Learning in Cancer Genomics. Cancer Genomics Proteomics. 2018;15:41–51.
15
 02
Feature
N rest task recovery
1
1. Mean (SM) mean 
N
Y
i 1
i Y = [HbO2]task 2. peak

2. Peak (SP) peak  max(Y ) 3. Standard derivation

3. Variance (SV) variance(Y )   (Y   ) 2

N 1. mean
4. Activation (SA)
4. activation 5. slope
Activation(Y) =
mean of [HbO2]task – mean of [HbO2]rest

5. Slope (SS)
Standard derivation (S.D) = 𝑉𝑎𝑟(𝑌)
NaseerN, QureshiNK, NooriFM, HongK. Analysis of Different Classification Techniques for Brain-Computer Interface.2016

16
 02
Feature
6. Skewness (SSK)
It is the degree of distortion from the normal
distribution.
 Y   3 
skewness(Y )  E   
   
7. Kurtosis (SK)
Kurtosis is all about the tails of the distribution.

 Y    4 
kurtosis(Y )  E   
   
x
Normalization x' 

NaseerN, QureshiNK, NooriFM, HongK. Analysis of Different Classification Techniques for Brain-Computer Interface.2016

17
02
Decision tree
Impurity  Gini impurity
c c
Gini   pi (1  pi )  1  pi2
i 1 i 1

(1) Question 1
Class 1 0  0  2  6  2 
Gini  1         0
Class 2 6  6   6  
(2) Question 2
Class 1 2  2  2  4  2 
Gini  1         0.44
Class2 4  6   6  

Gini  0 better than Gini  0.44

18
02
Subjects
Mental arithmetic & Calf restraint Concentration task

Healthy Healthy

Healthy control Healthy control

(HC) x13 (HC) x6

Migraine Migraine

Chronic migraine Chronic migraine

(CM) x9 (CM) x2
Medicine overuse headache AGE 20-60
Medicine overuse Headache
(MOH) x12 (MOH) x2

19
02

Results

01 Mental arithmetic

02 Calf restraint

03 Concentration task

20
02
Results Mental arithmetic Hemodynamic response Migraine HbO2
HHb
Healthy
HbO2
HHb

Mean change of concentration (μM)

Mean change of concentration (μM)

time (sec) time (sec)

Left side Right side
21
 02
Results Mental arithmetic Hemodynamic response Migraine HbO2
HHb
Healthy
HbO2
HHb

Mean change of concentration (μM)

Mean change of concentration (μM)

Migraine patients have lower stress threshold than healthy control,

thus they have more sensitive on stress-related event.
WangM, SuJ, ZhangJ, ZhaoY, YaoQ, ZhangQ. Visual cortex and cerebellum hyperactivation
during negative emotion picture stimuli in migraine patients. Nat Publ Gr. 2017;(April 2016):1-8.
21
02
Left Right
Results Mental arithmetic Feature

*p ≦0.05, **p ≦0.01, ***p ≦0.001

22
 02
*p ≦0.05, **p ≦0.01, ***p ≦0.001
Results Mental arithmetic Feature

A: anxiety
D: depression
GoM, BilbaoA. Orbitofrontal dysfunction predicts poor prognosis in chronic
migraine with medication overuse. 2011:459-466.

22
 02
Results Mental arithmetic Support Vector Machine

NIRS
Principal component 2

Principal component 2
low education
high education

Healthy N=13
Pearson correlation = 0.532
Principal component 1 Principal component 1 Significant = 0.09
Training accuracy Testing accuracy
85.2% 71.4%
mean/peak/skewness/kurtosis/slope/activatio
n
23
 02
Results Mental arithmetic Support Vector Machine

Non-NIRS
Principal component 2

Principal component 2
high anxiety, high depression
low anxiety, low depression

Principal component 1 Principal component 1

Training accuracy Testing accuracy
77.8% 71.4%
GoM, BilbaoA. Orbitofrontal dysfunction predicts poor prognosis in chronic migraine A/D/Answer rate/Correct rate/age
with medication overuse. 2011:459-466.
24
 02
Results Mental arithmetic Support Vector Machine

NIRS & Non-NIRS

Principal component 2

Principal component 2
1.00 0.33

0.00 0.67

Principal component 1 Principal component 1

Sensitivity 100%
Training accuracy Testing accuracy Specificity 67%
96.3% 85.7%
mean/peak/skewness/kurtosis/slope/activation/A/D/Answer rate/Correct rate/age
25
 02
Results Mental arithmetic Support Vector Machine

NIRS & Non-NIRS

Principal component 2

Principal component 2
CM

Principal component 1 Principal component 1

CM & MOH HC & MOH & CM MOH

mean/peak/skewness/kurtosis/slope/activation/A/D/Answer rate/Correct rate/age

25
02
Results Calf restraint Hemodynamic response Migraine HbO2
HHb
Healthy
HbO2
HHb

Mean change of concentration (μM)

Mean change of concentration (μM)

time (sec) time (sec)

Left side Right side
26
02
Left Right
Results Calf restraint Feature

*p ≦0.05, **p ≦0.01, ***p ≦0.001

27
 02
*p ≦0.05, **p ≦0.01, ***p ≦0.001
Results Calf restraint Feature

Russo A, Coppola G, Pierelli F, et al. Pain Perception and Migraine. Front

Neurol. 2018;9:576. Published 2018 Aug 2

28
 02
Results Calf restraint Support Vector Machine

NIRS
Principal component 2

Principal component 2
Pain stimulus is not suitable
for migraine detection

Principal component 1 Principal component 1

Training accuracy Testing accuracy
66.7% 57.1%
mean/peak/skewness/kurtosis/slope/activation
29
 02
Results Calf restraint Support Vector Machine

Non-NIRS Pain stimulus is not suitable

for migraine detection
Principal component 2

Principal component 2
vs

concentration
Principal component 1 Principal component 1 task
Training accuracy Testing accuracy
77.8% 57.1%

mmHg/pre-test NRS/post-test NRS/age

30
02
Results Concentration task Hemodynamic response Migraine HbO2
HHb
Healthy
HbO2
HHb

Mean change of concentration (μM)

Mean change of concentration (μM)

time (sec) time (sec)

Left side Right side
31
02
Results Concentration task Hemodynamic response Migraine HbO2
HHb
Healthy
HbO2
HHb

Mean change of concentration (μM)

Mean change of concentration (μM)

Healthy control have higher hemodynamic response

than migraine patients.

Left side Right side

31
02
Left Right
Results Concentration task Feature

Healthy control have

longer focus duration
*** than migraine patients.
***

*p ≦0.05, **p ≦0.01, ***p ≦0.001

32
02
Left Right
Results Concentration task Feature

*p ≦0.05, **p ≦0.01, ***p ≦0.001

33
 02
Results Concentration task Support Vector Machine

NIRS
Principal component 2

Principal component 2
1.00 0.17

0.00 0.83

Principal component 1 Principal component 1

Sensitivity 100%
Training accuracy Testing accuracy
Specificity 83%
91.7% 91.7%

mean/peak/skewness/kurtosis/slope/activation
34
02
Results
Support Vector Machine Decision tree

Mental arithmetic Training set Testing set Mental arithmetic Training set Testing set

NIRS 85.2% 71.4% NIRS 88.9% 71.4%

Non-NIRS 77.8% 71.4% Non-NIRS 77.8% 71.4%

NIRS & Non-NIRS 96.3% 85.7% NIRS & Non-NIRS 77.8% 71.4%

Calf restraint Training set Testing set Calf restraint Training set Testing set

NIRS 66.7% 57.1% NIRS 63.0% 57.1%

Non-NIRS 77.8% 57.1% Non-NIRS 63.0% 57.1%

NIRS & Non-NIRS 66.7% 42.9% NIRS & Non-NIRS 63.0% 57.1%

Concentration task Training set Testing set Concentration task Training set Testing set

NIRS 91.7% 91.7% NIRS 91.7% 83.3%

35
02
Summary

1 We build a migraine detection model successfully

2 Mental arithmetic can distinct the difference between chronic

migraine and medicine overuse headache

3 Mental stress has better performance than cuff pain

36
 ADHD Neurofeedback treatment
01 Introduce to ADHD

02 Experimental design

03 Results

ADHD: Attention deficit hyperactivity disorder

37
03
Introduction to ADHD

A mean worldwide prevalence of ADHD of 5–8% has been

estimated in children (aged <12 years).

Hyperactivity
Inattention & Impulsivity
Mix

38
03
Motivation
Neurofeedback treatment
Behavior therapy
Signal of brain
activation
Parent training in behavior therapy
Classroom behavior management

Medications
insomnia, stomach pain, loss of appetite,
nausea, vomiting, headache, vision
problems, increased heart rate, sweating Feedback
39
03
Experimental design
SNAP-IV Concentration task SNAP-IV

Baseline Regulatory trail Reinforcement

5 sec 30 sec 5 sec
Rest
20 sec
…… Repeat
28 times
40
03
Neurofeedback training HbO2 HHb

Phase I Phase II Phase III

Neurofeedback can improve concentration of ADHD patients.

【 HbO2 ↑ HHb ↓】
Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8
(unit: sec)
41
03
Neurofeedback training

Phase I Phase II Phase III

29.5 30.2 29.7

28.4
25.7
23.7
21.7

14.6

Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8

42
03
SNAP-IV assessment
26 item –Inattention (9); Hyperactivity/Impulsivity (9); Opposition/Defiance (8)

Pre-test Pre-test Post-test Post-test

Subject 1
(Parent) (Teacher) (Parent) (Teacher)
Inattention Subset 21 23 16 11
Hyperactivity/Impulsivity
Subset
3 13 5 4
Opposition/Defiance Subset 5 3 13 4

The higher the score(maximum 27 points),

the more severe the inattention.

43
03
SNAP-IV assessment
26 item –Inattention (9); Hyperactivity/Impulsivity (9); Opposition/Defiance (8)

Pre-test Pre-test Post-test Post-test

Subject 1
(Parent) (Teacher) (Parent) (Teacher)
Inattention Subset 21 23 16 11
Hyperactivity/Impulsivity
Subset
3 13 5 4
Opposition/Defiance Subset 5 3 13 4

The higher the score(maximum 27 points),

the more severe the hyperactivity/impulsivity.

43
03
SNAP-IV assessment
26 item –Inattention (9); Hyperactivity/Impulsivity (9); Opposition/Defiance (8)

Pre-test Pre-test Post-test Post-test

Subject 1
(Parent) (Teacher) (Parent) (Teacher)
Inattention Subset 21 23 16 11
Hyperactivity/Impulsivity
Subset
3 13 5 4
Opposition/Defiance Subset 5 3 13 4

The higher the score(maximum 24 points),

Bussing R, Fernandez M, Harwood M, et al. Parent and teacher SNAP-IV ratings
the more severe the opposition/defiance. of attention deficit hyperactivity disorder symptoms: psychometric properties and
normative ratings from a school district sample. Assessment. 2008;15(3):317–328.

43
03
Summary

1 The increase of the Δ[HbO2] represents the concentration

improved.

2 The scores of inattention and hyperactivity/impulsivity on the

SNAP-IV have significantly decrease.

44
 Conclusion
&
Future works

45
04

1 We can use mental-related task to extract feature for

migraine detection.

2 The difference between CM and MOH for what we found,

can help patients to manage their medicine dosage.

3 Neurofeedback is an feasible treatment for ADHD.

46
04
Skewness No significant difference in our
kurtosis experiment results

Reduce task execution time

Experiment

N. Naseer, K.S. HongClassification of functional near-infrared spectroscopy signals corresponding to the right-
and left-wrist motor imagery for development of a brain–computer interface.Neurosci. Lett., 553 (2013), p. 84

47
04
Improving accuracy
1. Motion correction
Detrend

2. Image classification
Algorithm
More channels
Increase spatial resolution
Deep learning
Statistical parameter mapping (SPM)
Convolution neural network (CNN)

47
04

Migraine ADHD

Neurological
disease

Subjects
NIRS --- Tourette
disease detection system syndrome Dementia

47
 Speaker: Wei-Chih Tang 唐偉智

63
48