NIRS: Functional NIRS: Functional NeuroimagingNeuroimaging

in the regulation of eating in the regulation of eating behaviorbehavior

Neuroscience Models of ObesityNeuroscience Models of Obesity

Jean-Claude Jean-Claude VouakouanitouVouakouanitou

ECNRECNR16133 Ventura Blvd, 716133 Ventura Blvd, 7thth Floor Floor

Encino, CA 91436Encino, CA 91436(818) 279-2490(818) 279-2490

Acknowledgements

Hershel Toomim, Biocomp Research Institute, Los Angeles

Athinoula A. Martinos Center for Biomedical Imaging

Massachusetts General Hospital, Harvard Medical School

E. Mark Haacke, Wayne State University

Vladislav Toronov, University of IllinoisE.Roy John, NYU School of MedecineJoel Lubar, University of Tennessee

Song Lai, University of ConnecticutHanli Liu, Group3 - BME 5345

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IntroductionIntroduction

Most studies in psychophysiology research have Most studies in psychophysiology research have used physical variables. used physical variables.

For example: heat and temperature, movement For example: heat and temperature, movement and speed, pressure and force, etc. Among and speed, pressure and force, etc. Among forces, that of gravity has been somewhat forces, that of gravity has been somewhat neglected.neglected.

This work was done to promote an interest in the This work was done to promote an interest in the principles of electrophysiology using the framework principles of electrophysiology using the framework of behavioral therapy.of behavioral therapy.

In thinking about individual personal weight the saying goes: In thinking about individual personal weight the saying goes:

“You are what you eat!”     “You are what you eat!”    

which we understand as "you weigh what you eat" which we understand as "you weigh what you eat" Your weight is determined by the quantity of the food you Your weight is determined by the quantity of the food you

eat.eat.

We realized that in order to make this method known We realized that in order to make this method known to the public and to emphasize its real significance, to the public and to emphasize its real significance, one should propose a simple example, usable by one should propose a simple example, usable by anyone and everyone. anyone and everyone.

People who use it are able to operate alone with a People who use it are able to operate alone with a minimum of instrumental support, whether or not minimum of instrumental support, whether or not they are under the observation of a monitor or a they are under the observation of a monitor or a therapist. therapist.

In the following discourse we will use "weight" and its In the following discourse we will use "weight" and its measure as a unique physical variable. measure as a unique physical variable.

Then comparing with a  model to be emulated, there are Then comparing with a  model to be emulated, there are repeating trials that reduce the gap between variables and the repeating trials that reduce the gap between variables and the model. model.

Finally, one learns the progressive correction of errors to be Finally, one learns the progressive correction of errors to be obtained in an instant gratification for each successful obtained in an instant gratification for each successful performance. performance.

All these things contribute to the basis of the All these things contribute to the basis of the electrophysiology method. electrophysiology method.

Obesity is an international Obesity is an international scourge…scourge…

We wanted:We wanted:

- - to assess side effects such as weight gain of patients to assess side effects such as weight gain of patients treated with antipsychotic medicationstreated with antipsychotic medications

- to explore the use of body weight or that of the daily to explore the use of body weight or that of the daily food ration as a physical dimension inserted in a food ration as a physical dimension inserted in a feedback loop.feedback loop.

This is another way to combat weight gain which is a pressing This is another way to combat weight gain which is a pressing social issue, especially in the United States where 127 million social issue, especially in the United States where 127 million adults are overweight, 60 million obese, and 9 million severely adults are overweight, 60 million obese, and 9 million severely obeseobese. .

……a public health problem, a a public health problem, a plagueplague, a world , a world epidemic.epidemic.

- 64.5% in the USA64.5% in the USA

- 8% in France8% in France

- 2% in China2% in China

- Developing countries are Developing countries are also affected by obesity.also affected by obesity.

Current weight of yourbody

Current weight of yourfood ration

To your ideal weight

Go up from

Reducing proportionally at Kthe

Up to its ideal value

To weigh the pounds which we must weigh eliminates a To weigh the pounds which we must weigh eliminates a certain number of immediate or future dangers:certain number of immediate or future dangers: the fatigue of the heart and/or the cardiovascular system,the fatigue of the heart and/or the cardiovascular system, the fatigue of the heart and/or the cardiovascular system,the fatigue of the heart and/or the cardiovascular system,

the fatigue of the the fatigue of the heart and/or the heart and/or the cardiovascular system,cardiovascular system,

the overload of the the overload of the vessels in lipids or usable vessels in lipids or usable deposits,deposits,

the accumulation of the accumulation of body fat,body fat,

a shortened life a shortened life expectancy…expectancy…

 Jim Pozarik / Getty Images file

We present a new approach, “We present a new approach, “Ponderal Neurobiological Ponderal Neurobiological Regulation”Regulation”, to , to explore the use of body weight in relation explore the use of body weight in relation to the daily food ration. to the daily food ration.

A big personA big person is a person is a person who who eats too much eats too much

Others say: “Let’s eat less sugar; let’s eat less fat; or don’t eat meat; so don’t Others say: “Let’s eat less sugar; let’s eat less fat; or don’t eat meat; so don’t absorb so many calories…”absorb so many calories…”

I say: I say: Weight is much easier to measure than calories.Weight is much easier to measure than calories.If a person begins eating too much of the wrong food and stops exercising, he If a person begins eating too much of the wrong food and stops exercising, he or she will develop habits that are difficult to change. Before long, obesity or she will develop habits that are difficult to change. Before long, obesity will take over.will take over.

- To be slim, it is necessary to be less bigTo be slim, it is necessary to be less big- To be less big, it is necessary to weigh lessTo be less big, it is necessary to weigh less- To weigh less, it is necessary to eat less.To weigh less, it is necessary to eat less.

Biopensum (from latin Biopensum (from latin ““penderependere”” = weight) is a = weight) is a method of assistance to the method of assistance to the weight decrease and its weight decrease and its control. control.

This method is not a This method is not a regimen. It is only a regimen. It is only a question of being or of question of being or of becoming very conscious of becoming very conscious of the weight of what one eats, the weight of what one eats, and to connect this weight to and to connect this weight to the pounds that one weighs.the pounds that one weighs.

Person Person Balance Balance Food Food Balance Balance PersonPerson

Our ponderal neurobiological regulation Our ponderal neurobiological regulation method of weight control is simple. It method of weight control is simple. It involves balancing the amount of food you involves balancing the amount of food you eat with the amount you weigh. eat with the amount you weigh.

Person Person Balance Balance Food Food Balance Balance PersonPerson

It involves becoming conscious of the It involves becoming conscious of the amount you eat and the amount your body amount you eat and the amount your body will absorb. will absorb.

if (Wa) = average current Weight,if (Wa) = average current Weight,

(Ra) = Ration average current day,(Ra) = Ration average current day,

(Wi) = ideal Weight (weight corresponding (Wi) = ideal Weight (weight corresponding to largest life expectancy) to largest life expectancy)

(Ri) = ideal Ration (ration corresponding at (Ri) = ideal Ration (ration corresponding at the maximum great life expectancy) the maximum great life expectancy) (Ra)/(Wa) = ka, expresses the current (Ra)/(Wa) = ka, expresses the current proportionality proportionality

or (Wa) = (Ra)/ka, or (Wa) = (Ra)/ka,

ka being a constant, personal and current. ka being a constant, personal and current. It has been able to be different in the past, It has been able to be different in the past, when you were two younger time. when you were two younger time.

Thus for the same reasons, there is a Thus for the same reasons, there is a balance, i.e. a relationship quite as fixed balance, i.e. a relationship quite as fixed between your ideal weight, or reference between your ideal weight, or reference weight, and that of your ideal ration: weight, and that of your ideal ration:

(Ri)/(wi) = ki (Ri)/(wi) = ki

or (wi) = (Ri)/ki, or (wi) = (Ri)/ki,

ki being also a personal constant. ki being also a personal constant.

This second ratio is practically the This second ratio is practically the same one with little of thing close that same one with little of thing close that the precedent but however not the precedent but however not completely. In any event one can to completely. In any event one can to write write

K = ka/ki (close to 1) K = ka/ki (close to 1) and (Ra)/(Wa) = K. (Ri)/(Wi) and (Ra)/(Wa) = K. (Ri)/(Wi) This relation has the merit to provide a This relation has the merit to provide a

first approximation of the weight of the first approximation of the weight of the ration which should be henceforth your ration which should be henceforth your daily ration ideal, at least with to leave daily ration ideal, at least with to leave the moment when you will have carried the moment when you will have carried out your adjustment ponderal, i.e. still out your adjustment ponderal, i.e. still when you lose sufficient to weigh your when you lose sufficient to weigh your ideal weight. Here this ration: ideal weight. Here this ration:

(Ri) = (wi). (Ra)/(Wa). K. (Ri) = (wi). (Ra)/(Wa). K.

Who can benefit from Who can benefit from Ponderal Neurobiological Regulation ?Ponderal Neurobiological Regulation ?

If your excess weight does not exceed 36% of If your excess weight does not exceed 36% of your ideal weight, Ponderal Neurobiological your ideal weight, Ponderal Neurobiological Regulation program can help you successfully Regulation program can help you successfully lose excess weight and keep it off for good!lose excess weight and keep it off for good!

For example, if your ideal weight is 120 – 150 lbs, For example, if your ideal weight is 120 – 150 lbs, and your weight 160 – 200 then we can help you and your weight 160 – 200 then we can help you achieve your weight goal.achieve your weight goal.

No regimen, but strong motivation is needed. No regimen, but strong motivation is needed. A simple formula can help you: you A simple formula can help you: you weigh 55 times (45 to 55 times, weigh 55 times (45 to 55 times, average is 50) what you absorbaverage is 50) what you absorb

In other words, ifIn other words, if you weigh 121 pounds, you weigh 121 pounds, you absorb 2.42 pounds of food a day (121 you absorb 2.42 pounds of food a day (121 lbs divided by 50).lbs divided by 50).

If you want to weigh 100 lbs instead your “ideal” If you want to weigh 100 lbs instead your “ideal” body weight would require that you absorb 2 lbs of body weight would require that you absorb 2 lbs of food a day. (100 divided by 50).food a day. (100 divided by 50).

To gradually lose the 21 lbs over time, you would To gradually lose the 21 lbs over time, you would need to reduce your intake by .40 lbs per day (2.42 need to reduce your intake by .40 lbs per day (2.42 lbs less 2 lbs).lbs less 2 lbs).

AverageAverage: In one week, you will lose : In one week, you will lose 2.2 lbs2.2 lbs. . It It corresponds with a daily reduction of between 220-corresponds with a daily reduction of between 220-440 oz. 440 oz.

But in the course of 24 hours, the significance of each But in the course of 24 hours, the significance of each weighing of body weight could seem difficult to weighing of body weight could seem difficult to understand because weight is constantly changing.understand because weight is constantly changing.

Current Current ingestasingestas in in ascending ascending thick lines : thick lines :

BB (breakfast), (breakfast), LL (lunch) and (lunch) and DD (dinner) (dinner)

ExcretaExcreta in in downward downward violet lines : violet lines : MM (micturitions)(micturitions), , MsMs (motions), (motions), etc.etc.

Materials and MethodsMaterials and Methods

We use two electroneuropsychobiological approaches :

Quantitative electroencephalography (qEEG)

Functional Near IR Spectroscopy (fNIRS)

To implement relationships To implement relationships between Synaptic Activity and between Synaptic Activity and Hemodynamic Responses, we Hemodynamic Responses, we used an integrated system used an integrated system combining Near Infrared combining Near Infrared Spectroscopy (NIRS) and Spectroscopy (NIRS) and electroencephalographic electroencephalographic activity (EEG).activity (EEG).

How to merge these two technologies ?

conventional radio-frequency RF conventional radio-frequency RF wireless and optical fibers.wireless and optical fibers.

diffusion diffusion equationequation kkabskk srtStrrtrrDtr

tc

,,,

1

13 rrrD scatabs

We have mathematical solutions

Poisson Equation &

The spectral range is 660 – 1100 nm. The spectral range is 660 – 1100 nm.

With different-measurement approaches With different-measurement approaches we can cover most of the adult head, we can cover most of the adult head, especially to collect optical data from especially to collect optical data from prefrontal, sensorimotor and visual prefrontal, sensorimotor and visual cortices in both hemispheres cortices in both hemispheres simultaneously. simultaneously.

We also can provide 3D images which offer high spatial and We also can provide 3D images which offer high spatial and temporal resolution of the brain and temporal resolution of the brain and images of hemodynamic images of hemodynamic parameters, suchparameters, such as: as:

cerebral changes in oxygenated (ΔO2Hb)cerebral changes in oxygenated (ΔO2Hb)

deoxygenated hemoglobin (ΔHHb)deoxygenated hemoglobin (ΔHHb)

total hemoglobin (ΔcHb = ΔO2Hb + ΔHHb)total hemoglobin (ΔcHb = ΔO2Hb + ΔHHb)

the mitochondrial enzyme cytochrome oxidase (or the mitochondrial enzyme cytochrome oxidase (or cytochrome aa3)cytochrome aa3) (ΔCtOx) in µmol, calculated with Lambert- (ΔCtOx) in µmol, calculated with Lambert-Beer's Principle.Beer's Principle.

We carried out simultaneous EEG-NIRS recordings We carried out simultaneous EEG-NIRS recordings

We developed a reflectance continuous-wave near-We developed a reflectance continuous-wave near-infrared spectroscopy topography system with multi-infrared spectroscopy topography system with multi-source (48 laser diodes) and six or eight objective source (48 laser diodes) and six or eight objective lenses.lenses.

Some wavelengths were emitting red and others near Some wavelengths were emitting red and others near infrared. infrared.

An integrated An integrated whole-head optical system whole-head optical system combining Near Infrared Spectroscopy (NIRS) and combining Near Infrared Spectroscopy (NIRS) and electroencephalographic activity (EEG) shows:electroencephalographic activity (EEG) shows:

A correlation between cognitive paradigms and A correlation between cognitive paradigms and hemodynamic signals.hemodynamic signals.

A collection of optical data from prefrontal, sensorimotor, A collection of optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously.and visual cortices in both hemispheres simultaneously.

48 light sources and six lenses video 48 light sources and six lenses video camera can also be placed in the NB camera can also be placed in the NB Optical Head to provide tomographic Optical Head to provide tomographic imaging of the brain.imaging of the brain.

This combines two technologies: This combines two technologies: conventional radio-frequency RF conventional radio-frequency RF wireless and optical fibers.wireless and optical fibers.

Light sources:

660/820 (2)660/820 (2)660/980 (2)660/980 (2)664/848 (2)664/848 (2)664/830 (1)664/830 (1)758/830 (8)758/830 (8)760/840 (3)760/840 (3)779/834 (1)779/834 (1)780/870 (2)780/870 (2)780/960 (2)780/960 (2)782/830 (1)782/830 (1)

Optical fibersOptical fibers snake over the scalp so snake over the scalp so that we can cover most of the adult that we can cover most of the adult headhead..

6 or 8 objective lenses 6 or 8 objective lenses of of infrared infrared video camera.video camera.

To have good To have good quality of quality of changes in changes in concentration concentration 24 pairs of laser diodes with intensity modulated at 110 MHz were were combined combined between 660 and between 660 and 980 nm.980 nm.

For acquiring high quality EEG and NIRS…For acquiring high quality EEG and NIRS…

Our whole-head optical system combines Near Our whole-head optical system combines Near Infrared Spectroscopy and electroencephalographic Infrared Spectroscopy and electroencephalographic activity activity so, so, the optical and electrical signals were the optical and electrical signals were recorded simultaneously.recorded simultaneously.

Top, Front and Side of the Top, Front and Side of the Neurobek box.Neurobek box.

The sensor image inside the The sensor image inside the camera uses advanced real-camera uses advanced real-time signal processing. time signal processing.

To test the models, a psychophysiological experiment To test the models, a psychophysiological experiment was carried out with fwas carried out with five groups:ive groups:

Healthy volunteersHealthy volunteers (BMI < 24 kg/m2, 3M/5F, age 46 (BMI < 24 kg/m2, 3M/5F, age 46 ± 9 y, body fat 21 9 y, body fat 21 ± 6%), 6%),

Type 2 diabetes mellitus and PADType 2 diabetes mellitus and PAD (n 5, 2M/3F) (n 5, 2M/3F) Obese onlyObese only (BMI>35 kg/m2, 5M/7F, age 45 (BMI>35 kg/m2, 5M/7F, age 45 ± 6 y, body fat: 42 6 y, body fat: 42 ± 5%). 5%).

Bipolar disorderBipolar disorder (n 6, 2M/4F) (n 6, 2M/4F)

SchizophreniaSchizophrenia (n 5, 3M/2F) (n 5, 3M/2F)

Group BMI N Age Body FatGroup BMI N Age Body Fat

Healthy volunteers Healthy volunteers 24 kg/m2 3M/5F24 kg/m2 3M/5F 46±9 y46±9 y 21±6% 21±6%

Type II diabetesType II diabetes 35 kg/m2 2M/3F35 kg/m2 2M/3F 65±7 y 33±7%65±7 y 33±7%

ObeseObese 35 kg/m2 5M/7F35 kg/m2 5M/7F 55±6 y 42±5%55±6 y 42±5%

Bipolar disorderBipolar disorder 30 kg/m2 2M/4F30 kg/m2 2M/4F 63±8 y63±8 y 35±9% 35±9%

SchizophreniaSchizophrenia 30 kg/m2 3M/2F 29±5 y30 kg/m2 3M/2F 29±5 y 37±8% 37±8%

Subjects in this study consumed an herbal tea containing pBFKT 750 (kolokoto tea, 0.39 US gal) daily for six months.

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BFKT™ imported from Congo under CITES & USDA.

MicroCog MicroCog Glycosylated hemoglobin Glycosylated hemoglobin

(HbA1C)(HbA1C) Liver and renal functions Liver and renal functions Body fat measurementsBody fat measurements The measuring tapeThe measuring tape

were assessed and were assessed and compared at the baseline, compared at the baseline, at a 3 month and at a 3 month and at a 6 at a 6 month period.month period.

Prisca, 28 y. o Weight: 264 lbs, Height: 5’7” BMI = 40.91Prisca, 28 y. o Weight: 264 lbs, Height: 5’7” BMI = 40.91

The daily body weighing of Prisca and the immediate The daily body weighing of Prisca and the immediate notation of the resulting weight. notation of the resulting weight.

Became her motivational desire to obtain a Became her motivational desire to obtain a progressive and finally sufficient weight loss. She progressive and finally sufficient weight loss. She achieved this, thanks to a daily adjustment and an achieved this, thanks to a daily adjustment and an adapted  food rationing. adapted  food rationing.

Beginning on Beginning on November 1November 1stst 2006 2006

End on May 30End on May 30thth 2007 2007

Target Period Intake solution1st target  214 lbs Jan.30th 3.15 2.23 Av.2 ,72nd target  187 lbs Feb 28th 2.90 2.56 Av 2.73rd target  161 lbs March 30th Av 2.654th target 152 lbs May 15th

Av. 2.56lost : between 119 and 75 lbs Average: 97 lbs 16 lbs per month.

Whatever long the Whatever long the reduction period has reduction period has been, it has to be been, it has to be followed  by a followed  by a Stabilization period.Stabilization period.

For many people, the For many people, the end of a weight loss end of a weight loss period or that of a period or that of a diet of ponderal diet of ponderal reduction means the reduction means the end of a small torture. end of a small torture. Many will return at Many will return at last to previous last to previous habits. In a very short habits. In a very short time they will be back time they will be back to their initial weight, to their initial weight, the one at which they the one at which they were  before ponderal were  before ponderal reduction.reduction.

Prisca showing her weight losePrisca showing her weight lose

October 2006 October 2006

5’7” 264 lbs5’7” 264 lbs

January 2007 January 2007

175 lbs 175 lbs

April 2007April 2007

145 lbs145 lbs

ResultsResults Results shown an increase (p < 0.005) in Results shown an increase (p < 0.005) in

cerebral blood volume and COV in areas cerebral blood volume and COV in areas of the prefrontal, parietal and temporal of the prefrontal, parietal and temporal cortex. cortex.

This blood increase occurs during a This blood increase occurs during a calculation and verbal-fluency tasks while calculation and verbal-fluency tasks while it decreases in the orbito-frontal of an it decreases in the orbito-frontal of an obese individual compared to a healthy obese individual compared to a healthy volunteer (P < 0.05). volunteer (P < 0.05).

This study provides preliminary This study provides preliminary evidence that patients suffering from evidence that patients suffering from type II diabetes and obesity had higher type II diabetes and obesity had higher fasting plasma glucose (85.2 fasting plasma glucose (85.2 ± 5.4 vs. 5.4 vs. 82.5 82.5 ± 8.5 mg/dl; P = 0.0003) 8.5 mg/dl; P = 0.0003)

and insulin concentrations (6.9 and insulin concentrations (6.9 ± 4.1 vs. 4.1 vs.

2.8 2.8 ± 1.9 microU/ml; P < 0.0001). 1.9 microU/ml; P < 0.0001).

Other changes values from 8.2 to 4.7 for Other changes values from 8.2 to 4.7 for HbA1C whereas for BMI from 35 and HbA1C whereas for BMI from 35 and more to 24 and 22.5 were observed. more to 24 and 22.5 were observed.

Some tasks of Horatherapy such as the Some tasks of Horatherapy such as the “1” and cognitive enhancing exercises “1” and cognitive enhancing exercises increase both CBV and COV in the increase both CBV and COV in the affected prefrontal cortex of patients affected prefrontal cortex of patients with obesity.with obesity.

Quantitative analysis of [O2Hb] & Quantitative analysis of [O2Hb] & [HHb][HHb]

Subjects[O2Hb]0

(M)

[HHb]

0

(M)

b]

(M)b]

(M)P%

CP R% CR APARr

with R

r

without R

Type II diabetes Mellitus

00.6±1.2

-1.19±0.27

0.007-0.25±0.25

0.97 0.95 0.83 0.902.40

±1.180.784 0.784

Obesity30.1±2.7

6.0±1.8

0.52 0.23 3.49 0.96 0.920 0.962.64

±0.350.976 0.9375

Bipolar disorder &

Shizophrenia

0.009±4.3

6.3±1.5

0.41 0.25 3.570.94

0.57 0.452.37

±1.640.989 0.8937

Healthy31.5±3.2

12.7±1.4

0.39 0.37 3.390.82

0.82 -0.26

3.72 ±0.89

0.8685 0.8451

Statistics of physiological Statistics of physiological parameters parameters

  

Total  Right Middle Left

Scalp Brain Scalp Brain Scalp Brain Scalp brain

StOx (%)

61.25 ± 3.57

62.38 ± 5.82

61.69 ± 3.04

64.73 ± 5.78

60.78 ± 3.14

64.38 ± 5.93

61.07 ± 3.85

65.68 ± 5.83

tHb(M)

47.12±10.7

73.85 ± 12.8

56.67 ± 8.13

78.96 ± 12.14

53.67 ± 12.8

75.65 ± 14.29

66.73 ± 12.64

75.93 ± 14.96

O2Hb(M)

37.38± 7.81

54.71± 11.5

43.61 ± 5.75

58.34 ± 9.05

38.42 ± 8.23

56.29 ± 12.60

38.93 ± 9.14

56.57± 12.63

HHb(M)

15.59 ± 3.25

19.56± 5.84

15.83± 3.25

19.87± 5.62

14.69± 3.53

19.67± 5.89

15.79± 3.46

19.71± 6.95

DPF=758nm

6.09 ± 0.71

4.89 ± 1.35

6.17 ± 0.85

4.76 ± 1.26

6.15 ± 0.67

4.66 ± 1.92

5.98 ± 0.91

4.75 ± 1.35

conclusionsconclusions Obesity is mostly caused by overeating. Obesity is mostly caused by overeating.

Ponderal neurobiological regulation (pBFKT) can be Ponderal neurobiological regulation (pBFKT) can be used as an effective way to combat weight gain with used as an effective way to combat weight gain with motivation. motivation.

Bridelia ferruginea have been validated for treating Bridelia ferruginea have been validated for treating type II diabetes, overweight and obesity. type II diabetes, overweight and obesity.

Near Infrared Opitical Imaging can be used to Near Infrared Opitical Imaging can be used to pinpoint the regulation of eating behavior.pinpoint the regulation of eating behavior.

Thank you very much !Thank you very much !

ACKOWLEDGEMENTThis research is supported by Electrophysiology & Clinical Neuroscience Research (ECNR).© Los Angeles, Encino, 2006, 2007