International Summer School and Workshop on Brain Dynamics July 23 - 28 , 2012 ITAP, , Marmaris, TURKEY

Murat Ozgoren, MD PhD Dokuz University, Medical Faculty, Biophysics Department, Izmir, Turkey

Heraclitus ; c. 535 c. 475 BCE

Everything changes and nothing remains still ... and ... you cannot step twice into the same

Heraclitus (figured by Michelangelo) ITAP 2012 Ozgoren

Ephesos

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Brain Biophysics Workshops

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Brain biophysics, psycho- EXAMPLE Dichotic (brain asymmetry)

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Brain Biophysics Research Area

Different domains in Brain Biophysics

fNIR

Termal

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Invasive

Non-Invasive

Log time (s)

EEG matrix (1011 neurons) Quantum computers

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Solution EMISU

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Pinball

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Dichotic Paradigm:

A Multidisciplinary and Translational Journey

Dichotic Stimuli

L R

BA DA TA KA GA PA KA GA

%

Hugdahl, K., Carlsson, G., Uvebrant, P. und Lundervolt, A. J. (1997) Dichotic listening performance and intracarotid amobarbital injections in children / adolescents: Comparisons pre- and postoperatively. Arch. Neurol., 54: 1494-1500. Hugdahl,K. (2005). Symmetry and asymmetry in the human brain. European Review, 13:2;119-133. ITAP 2012 Ozgoren

Methods

144 stimuli (with left and right hand)

The subject responds to firstly heard or best heard CV

The personal observations are also noted

Left ear

Right ear

GA - DA

KA - TA -

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Electrophysiology of DL

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Figure. The Dichotic Listening response waveform and its corresponding map during REA condition. (A) The evoked potential indicating the N1P2 and LN sections. (B) The N1P2 2D map (C) LN 2D map. The amplitude is presented by means of a graded scale; the corresponding highest peak effect is shown by means of a white contour line. ITAP 2012 Ozgoren

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Current applications

Schizophrenia Other neurocognitive deisorders

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Brain responsiveness

& Application of auditory stimulations in sleep

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HOW BIS and other methods (i.e. fNIR) can be used in sleep ?

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BIS - BISPECTRAL INDEX-

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A typical sleep stage and BIS monitor result chart

r=0.84

Red: BIS Values Blue: EMG Black: R&K Stages

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BIS Indexes vs Sleep Stages

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Multidimensional Scope Brain Responsiveness

Multimeter, Electrophysiological

Fuzzy Logic,

MicroMacro State Analysis

Evoked Immediate

Induced Midterm

Reactive longterm

Induced Midterm

Reactive longtermBiorhythm; Core body temperature, Sleep stage etc.

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Biorhythm; Core body temperature,

Thermal Biorhtym Analysis

Evoked Immediate

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Material and Methods 40 channel EEG (International 10-10 system)

Nuamps 0.5-200 Hz band pass 1000 Hz sampling frequency

EOG EMG EMISU Embedded Microcontroller Stimulation Unit BIS Bispektral Index (Aspect A2000)

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STIMULATIONS

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STIMULATIONS

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DT AEP DL MMN AERP

DT DL AEP AERP

Deep Light REM

Deep Light REM

Deep Light REM

Deep Light REM

-500 -250 0 250 500 750 1000 1250 1500

90

80

70

60

50

40

30

ms

GRANDAVERAGE AEP N=12

AEPs under the scope of BIS

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Components Definitions Source

N1 A negative component evoked 75-150 ms after the auditory stimulation. Auditory N1 response is the leading step in the conscious audiory pathway.

P2 Related to deepening of sleep.

N300 influenced by intensity and frequency changes, and the content of the stimulation.

P450 Evoked after Non-Target stimulus .

N550 Effected from the meaning and the physical properties of the stimulus.

P900 (P750) Related to deepening and maintaining of sleep processes.

.

AEPs in SLEEP STUDIES

N1

P2

N300

P450

N550

P900 (P750)

RESULT

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Light sleep Deep Sleep

Light Sleep

Deep Sleep

2.500 V

_

+ -500 -250 0 250 500 750 1000 1250 1500 ms

Simple and Complex Auditory Evoked Potentials

N1

P2

N300

P450

N550

P900

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Induced Midterm

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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- ALYI _ SLEEP 1 -

0102030405060708090

100

1 42 83 124 165 206 247 288 329 370 411 452 493 534 575 616 657

Time

0 5 10 15 20 25 30 35 40 45 0 5 10 15 20 25 30 35 40 45 50

DT AEP DL MMN AERP

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ON THE ANALYSIS OF BIS STAGE EPOCHS VIA FUZZY CLUSTERING

Ulutagay1 2, Sibel Kocaaslan2

Figure 4. Clustering results of FCM algorithm for 8 clusters.

Reactive longterm

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Multidimensional Scope of Brain Responsiveness

Multimeter, Electrophysiological

Fuzzy Logic,

MicroMacro State Analysis

Evoked Immediate

Induced Midterm

Reactive longterm Biorthtym; Core body temperature, Sleep stage etc.

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UYKU

Klasik uyku evrelerinde

Uykunun ilk ve

UP

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Take home questions

Vigilance &current mental/brain state Is it just the night&sleep relation ? Is it stable throughout the day? Sustained Mental Effort should be studied as a parameter next to

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Consciousness and brain function assesment cont.

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Pergamum Aesclepion

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Anaxagoras, Hippocrates, Heraphilus and Galen.

Incubation was commonly practiced in Pergamum Asclepion to trigger the healing at subconscious level. The details are provided by means of excellent records of a famous hypochondriac: Aristides (Publius Aelius Aristides, 2nd c AD)

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Hipnotic/sedative

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Gevher Nesibe (1261)

Furthermore, the

beleived to be rooted back to Pergamum, leading to annual international convention of psycho- therapists

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ITAP 2012 Ozgoren murat.ozgoren@deu.edu.tr

2010

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Journey in space

Journey in time

Different Conscious States

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Consciousness

Coma

Stupor

Somnolance

Lethargy

Awake

Anesthesia

Sleep

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Calculation capacity 100 billion neurons 1000-10000 synapses 100 billion X 200 signals/second X 1000 synapses = 20 millionXbillion calculations/second

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Different Conscious States

M. Ozgoren, Brain biophysics approach to brain functioning via dichotic listening paradigm, IJ. Psychophysiol ; 69:188-189.

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OR Experiments

100

0

Freye, E. 2005. Cerebral Monitoring in the OR and ICU. Springer, Dordrecht, The Netherlands.

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TACTILE-1 ITAP 2012 Ozgoren

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Anesthesia

BIS & Sleep

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Sleep &BIS

r=0.84

Red: BIS Values Blue: EMG Black: R&K Stages

Anesthesia N1

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Sleep N1

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Sleep N1 AEP and DL under Anesthesia

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AEP and DL during Sleep

Localization of activity

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Sleep (evoked activity ), BA7

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Anesthesia (evoked activity ), BA7

What about spindle oscillations?

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Spindle Oscillations

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Single Subject Anesthesia

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(Cavanna and Trimble 2006).

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PRECUNEUS

PRECUNEUS Shulman et al. (1997) meta-analysis functional imaging studies, cortical activations across visual tasks => signal decreases, involving the frontoparietal areas and including the precuneus, during the performance of goal-directed actions when compared with passive stimulus viewing (Cavanna and Trimble 2006). Dorsolateral prefrontal cortex and Precuneus interaction (Kjaer et al 2001) C. J. Stam =>

Is locating the electrophysiological activity the end of the story?

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EEG matrix (1011 neurons etc.)

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Death Gazzaniga The Ethical Brain Today, where a definition of the moment of

death is required, doctors and coroners usually turn to "brain death" or "biological death" to define a person as being clinically dead; people are considered dead when the electrical activity in their brain ceases. It is presumed that an end of electrical activity indicates the end of consciousness. However, suspension of consciousness must be permanent, and not transient, as occurs during certain sleep stages, and especially a coma. In the case of sleep, EEGs can easily tell the difference

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Death Thermoregulation

Rudolf Clausius founding thermodynamicist and originator of the concept of entropy

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BASIC => CLINICAL

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FUTURE RESEARCH AGENDA

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Thermal Biorhtym Analysis

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S l eep

Polysomno-

graphy BIS/fNIR

Dynamic Thermal

Recording

Thermoregulation (36.5-37.5 C)

http://okfirst.mesonet.org/train/meteorology/HeatTransfer.html (16.04.2010) http://clow.ipsd.org/images/clipart/sweating.gif (16.04.2010)

How and why ?

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WHAT NOW?

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Brain Biophysics Research Area

Joint Planning

Research Education Innovation ITAP 2012 Ozgoren

Effect of Body Position on NIRS Based Hemodynamic

Measures from Prefrontal Cortex

Murat Ozgoren1, Merve Tetik1, Kurtulus Izzetoglu2, Adile Oniz1, and Banu Onaral2

1 Dokuz Eylul University, Faculty of Medicine, Department of Biophysics Izmir, Turkey

2 Drexel University, School of Biomedical Engineering, Science & Health Systems,

Philadelphia, US H. Zhang et al. (Eds.): BICS 2012, LNAI 7366, pp. 138 146,

2012. Verlag Berlin Heidelberg 2012

Neuroimaging Methods

EEG MEG PET SPECT

fMRI

NIRS/fNIRS

-0,5

0

0,5

1

1,5

2

-4 -3 -2 -1 0 1 2 3 4

millisecond second hour day

Temporal Resolution (log time)

MEG/EEG

NIRS PET/SPECT

Diffuse Optical fMRI

Figure 1.

- Functional near infrared spectroscopy (fNIRS) based optical brain imaging technique has been widely used as a non-invasive measurement method to monitor human brain activity.

- Diffuse optical monitoring is determined by two factors that absorbed and scattering light.

H. Zhang et al. (Eds.): BICS 2012, LNAI 7366, pp. 138 146, 2012.

Verlag Berlin Heidelberg 2012

Effect of Body Position on NIRS Based Hemodynamic Measures from Prefrontal Cortex

Ozgoren, M., Tetik, M., Izzetoglu, K., Oniz, A., Onaral, B.

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H. Zhang et al. (Eds.): BICS 2012, LNAI 7366, pp. 138 146, 2012.

Verlag Berlin Heidelberg 2012

Effect of Body Position on NIRS Based Hemodynamic Measures from Prefrontal Cortex

Ozgoren, M., Tetik, M., Izzetoglu, K., Oniz, A., Onaral, B.

Cardiology Department, Tilt Table Test Room

Figure 9. ITAP 2012 Ozgoren

H. Zhang et al. (Eds.): BICS 2012, LNAI 7366, pp. 138 146, 2012.

Verlag Berlin Heidelberg 2012

Effect of Body Position on NIRS Based Hemodynamic Measures from Prefrontal Cortex

Ozgoren, M., Tetik, M., Izzetoglu, K., Oniz, A., Onaral, B.

Experiment 2

00

450

900

Seventeen healthy subjects [eleven females ( : 28.81, SD: 8.28) and six males ( : 32.17, SD: 11.27)] were investigated.

Figure 11.

Eyes opened

Eyes closed

(2 min for each session)

Figure 12.

The volunteer first lay in supine position, then, moved to the tilted (450) position, moved to the vertical position. Afterwards there was a dynamic session where the subject was moved during recording from vertical to supine position and back to vertical position (900-00 900). These two dynamic position change recordings continued for 5 minutes.

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Blood Pressure

*p < .05; 450 < 900 (DB)

Pulse Oxymeter (SpO2)

Effect of Body Position on NIRS Based Hemodynamic Measures from Prefrontal Cortex

Ozgoren, M., Tetik, M., Izzetoglu, K., Oniz, A., Onaral, B.

H. Zhang et al. (Eds.): BICS 2012, LNAI 7366, pp. 138 146, 2012.

Verlag Berlin Heidelberg 2012

Changing of axis & fNIRS

Experiment 2

Hb HbO2

*p < .05; 00 > 450 (HbO2)

900 00 > 900 00 900 (HbO2)

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BRAIN (Responsiveness) vs BIORHYTHMS

Evoked Immediate

Induced Midterm

Reactive longterm

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Hours to days (circadian, seasonal)

Minutes to hours (ultradian, circadian)

Milliseconds to seconds (microdian?)

BRAIN BIORHYTHMs Hours to days (circadian) Minutes to hours

(ultradian) Milliseconds to minutes

(microdian?)

Heraclitus ; c. 535 c. 475 BCE

Everything changes and nothing remains still ... and ... you cannot step twice into the same

Heraclitus (figured by Michelangelo) ITAP 2012 Ozgoren

Ozgoren 2012

Thank you

ederim

murat.ozgoren@gmail.com ITAP 2012 Ozgoren

ACKNOWLEDGEMENT The researchers are thankful to Onur ,

for their support in design arrangements. They also appreciate collaboration of Dr. of Neurology Department, Sleep Division. TUBITAK 108S113 BOCHUM BERGEN DREXEL HOKKAIDO JSRS TSRS

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References

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"Brain Asymmetry Measurement Using EMISU (Embedded Interactive Stimulation Unit) in Applied Brain Biophysics". Comput Biol Med; doi:10.1016/j.compbiomed.2009.07.001

Epochs via Fuzzy Clustering", Biomedizinische Technik / Biomedical Engineering, (in press).

Light of Bispektral Index", Turkish Clinical Medical Sciences, (in press).

"The Assesment of Acoustical and Electromagnetic Noise on EEG Monitorization During Spinal Surgery Operations", Journal of Neurological Sciences (Turkish), (in press).

-REM Sleep Staging with Electroencepholography Bispectral Index", Sleep and Biological Rhythms, 6, 249-255 (2008).

Memory Measurements in Anesthesia", Journal of Neurological Sciences, 25(4), 17: 290-300 (2008). ITAP 2012 Ozgoren

- -REM Sleep Staging with

Sleep and Biological Rhythms, 6, 249-255 (2008). -

Journal of Neurological Sciences, 25(4), 17: 290-300 (2008). - Trial-by-Trial ERP Analyses Reveal Intra- Neuropsychologia, 47(2), 536-545 (2009). -

Comput Biol Med; doi:10.1016/j.compbiomed.2009.07.001 -

-

14th National Biomedical Engineering Meeting, BIYOMUT 2009. 20-22 May 2009 Page(s):1 3, doi: 10.1109/BIYOMUT.2009.5130383(2009). - Prof. Dr.; Sibel Kocaaslan, MSc., ON THE ANALYSIS OF BIS STAGE EPOCHS VIA FUZZY CLUSTERING, - Biomedizinische Technik / Biomedical Engineering, in press.