Lectu

re 2

Chapte

r 4: T

he O

rigin

of

Bio

pote

ntials

Dr.

Nitis

h V

. T

hakor

Bio

medic

al In

str

um

enta

tion

JH

U A

pplie

d P

hysic

s L

ab

Intr

od

uction

Biopotentials arise from cells, and more generally from organs. They hold rich

physiological and clinical information. For example, action potentials give

information on fundamental ion channel biophysics and molecular aspects of

any pathology. Biopotentials from the organs of the body are of clinical

diagnostic significance.

Examples:

1.Action Potentials from Cells (and 3 Nobel prizes!)

1.Neuronal action potential (history of Squid axon and Hodgkin-Huxley work)

2.Patch clamp technique and single channel recording (Sakman-Neher)

3.Water channel work of Peter Agre (JHU)

2.Biopotentials from the organ/body

1.Electrocardiogram (ECG) from heart -> use in heart attack, pacemakers

2.Electroencephalogram (EEG) from brain -> use in epilepsy, brain trauma

3.Electromyogram (EMG) from muscle -> use in muscle diseases, prosthesis

4.Others…

Ele

ctr

ical A

ctivity o

f E

xcitable

Ce

lls

•E

xcita

ble

ce

lls

–E

xis

t in

nerv

ous,

muscula

r

and g

land

ula

r tissue

–E

xh

ibit a

resting p

ote

ntial

and a

n a

ction p

ote

ntia

l

–N

ecessary

for

info

rmatio

n

transfe

r (e

.g.

sensory

info

in n

erv

ous s

yste

m o

r

coord

inatio

n o

f blo

od

pum

pin

g in

the h

eart

)

0 m

V

-70

mV

depola

rization:

Na+

influx

repola

rization:

K+

outflu

x

Na+

Ca+

+

K

+

Neuronal action potential

Cardiac action potential

repola

rization:

K+

outflu

x

Resting v

s. A

ctive S

tate

•R

esting S

tate

–S

tea

dy e

lectr

ica

l po

ten

tia

l o

f d

iffe

ren

ce

be

twe

en

in

tern

al a

nd

exte

rna

l e

nvir

on

me

nts

–T

yp

ica

lly b

etw

ee

n -

70

to

-9

0m

V,

rela

tive

to

the

exte

rna

l m

ed

ium

•A

ctive S

tate

–E

lectr

ica

l re

sp

on

se

to

ad

eq

ua

te s

tim

ula

tio

n

–C

on

sis

ts o

f “a

ll-o

r-n

on

e”

actio

n p

ote

ntia

l a

fte

r

the

ce

ll th

resh

old

po

ten

tia

l h

as b

ee

n r

ea

ch

ed

Record

ing o

f A

ction P

ote

ntial

•T

yp

ica

l

reco

rdin

g

syste

m (

top

)

usin

g

mic

roe

lectr

od

e

•R

eco

rdin

g o

f

an

actio

n

po

ten

tia

l in

ne

rve

ce

ll

(bo

tto

m)

Resting M

em

bra

ne P

ote

ntial

•C

ell

pote

ntial is

a f

unctio

n o

f m

em

bra

ne p

erm

eab

ility

and

conce

ntr

ation g

rad

ient to

various m

ole

cu

les (

i.e.

K+, N

a+,

Cl- ,

and C

a2+)

•E

qu

ilibri

um

pote

ntial is

the m

em

bra

ne p

ote

ntial at

whic

h

a g

ive

n m

ole

cule

has n

o n

et

movem

ent

acro

ss the

mem

bra

ne

–N

ern

stE

quation (

in V

olts a

t 37 o

C):

–n

is the v

ale

nce o

f K

+, [K

] iand [K

] oare

the intr

a-

and e

xtr

acellu

lar

concentr

ations, R

is the u

niv

ers

al gas c

onsta

nt, T is the a

bsolu

te

tem

pera

ture

in K

elv

in, F

is the F

ara

day c

onsta

nt, a

nd EK

is the

equili

brium

pote

ntial

io

io

K

KK

KK

nF

RT

E]

[

][

log

0615

.0

][

][

ln10

==

Resting M

em

bra

ne P

ote

ntial

•E

qu

ilib

riu

m m

em

bra

ne

re

stin

g p

ote

ntia

l w

he

n

ne

t cu

rre

nt

thro

ug

h t

he

me

mb

ran

e is z

ero

–P

is t

he p

erm

eab

ility

coeff

icie

nt

of th

e g

ive

n ion

•F

acto

rs in

flu

en

cin

g io

n f

low

acro

ss the

m

em

bra

ne

–D

iffu

sio

n g

rad

ients

–In

ward

ly-d

irecte

d e

lectr

ic fie

ld

–M

em

bra

ne s

tructu

re

–A

ctive t

ransport

of io

ns a

gain

st

ele

ctr

ochem

ical

gra

die

nt

++

++

=o

Cl

iNa

iK

iCl

oNa

oK

Cl

PNa

PK

P

Cl

PNa

PK

P

FRT

E]

[]

[]

[

][

][

][

ln

Action P

ote

ntial

•S

tim

ula

tio

n o

f e

xcita

ble

ce

lls c

au

se

s “

all-

or-

no

ne

”re

sp

on

se

•A

t th

resho

ld,

the

me

mb

ran

e p

ote

ntia

l ra

pid

ly

de

po

lari

ze

s d

ue

to a

ch

an

ge

in

me

mb

ran

e

pe

rme

ab

ility

–P

Na

sig

nific

antly incre

ases c

ausin

g t

he m

em

bra

ne

pote

ntia

l to

appro

ach E

Na

(+60m

V)

•A

de

laye

d in

cre

ase

in

PK

ca

use

s

hyp

erp

ola

riza

tio

na

nd

a r

etu

rn t

o r

estin

g

po

ten

tia

l

Action P

ote

ntial and

Ionic

Con

du

cta

nce

•g

Na

and g

Kare

the

cond

ucta

nce o

f

Na

+an

d K

+

•v

is the

mem

bra

ne

pote

ntia

l

•A

bso

lute

and

rela

tive

refr

acto

ry

peri

ods

Circuit D

iagra

m o

f M

em

bra

ne

•N

etw

ork

equiv

ale

nt

circuit

of

a s

mall

incre

me

nt

of

mem

bra

ne

•N

ote

critica

l ele

ments

: extr

ace

llula

r-in

tracellu

ar

–M

em

bra

ne c

apacitance, voltage d

ependent io

n c

hannel

conducta

nce, re

vers

e p

ote

ntial fo

r each ion c

hannel (N

a, K

, …

)

Neuro

n S

chem

atic

•C

ond

uctio

n

alo

ng a

nerv

e–

Result o

f depola

rization o

f sm

all

patc

h o

f m

em

bra

ne

–C

onduction

alo

ng a

nerv

e

fiber

(more

genera

lly a

xons

and d

endrite

s)

–S

altato

ryconduction a

long

myelin

ate

dfibers

in

nerv

es, spin

al

cord

Org

aniz

ation o

f P

eri

phe

ral N

erv

ous

Syste

m

•R

efle

x a

rc

–S

ense o

rgan (

e.g

. re

cepto

rs)

–S

ensory

nerv

e (

transfe

rs info

rmation f

rom

recepto

r to

CN

S)

–C

NS

(i.e.

info

rmation p

rocessin

g s

tation)

–M

oto

r nerv

e (

transfe

rs info

rmation f

rom

CN

S t

o

eff

ecto

rorg

an)

–E

ffecto

rO

rgan (

i.e.

muscle

s)

•S

imp

lest e

xa

mp

le

–K

ne

e r

eflex

Reflex A

rc

Org

aniz

ation o

f P

eri

phe

ral N

erv

ous

Syste

m

•Ju

nctio

na

lT

ran

sm

issio

n

–C

om

mun

ication lin

ks b

etw

een

•N

euro

ns a

nd n

euro

n c

onnte

ctions: calle

d synapses

•N

euro

ns a

nd e

ffecto

rorg

ans, calle

d end-plate region

–E

lectr

oche

mic

al tr

ansm

issio

n v

ia n

euro

transm

itte

rs:

(Inhib

itory

and E

xcitato

ry;

chem

ical, g

aseo

us)

•A

cety

lcholin

e

•G

AB

A

•G

luta

mate

•D

opam

ine

•N

itric o

xid

e Pre

synaptic r

ele

ase o

f

neuro

transm

itte

r

Posts

ynaptic c

hannel

openin

g a

nd m

em

bra

ne

depola

rization

Tra

nsm

issio

n o

f action

pote

ntial

Ele

ctr

oneuro

gra

m(E

NG

)

•M

easure

s n

erv

e f

ield

pote

ntia

ls

•U

se o

f nee

dle

ele

ctr

odes

•S

tim

ula

te the p

eri

ph

era

y

and m

easu

re t

he

cond

uctio

n v

elo

city

•U

se

d in a

ssessin

g

neuro

muscula

r dis

ord

ers

:

peri

ph

era

l nerv

e inju

ry,

muscula

r dystr

ophy

Ele

ctr

om

yogra

m(E

MG

)

•M

easure

s m

uscle

activity

•R

ecord

in

tram

uscu

larl

y

thro

ugh n

eed

le

ele

ctr

odes

•R

ecord

surf

ace

EM

G u

sin

g

ele

ctr

odes o

n

bic

eps,

tric

eps…

•U

se in m

uscula

r dis

ord

ers

, m

uscle

base

d p

rosth

esis

–pro

sth

etic a

rm, le

g

Anato

my o

f th

e H

eart

http://info

.med.y

ale

.edu/intm

ed/c

ard

io/e

cho_atlas/r

efe

rences/g

raphic

s/h

eart

_anato

my.g

if

Ele

ctr

ical B

ehavio

r of th

e H

eart

•C

ond

uctio

n

syste

m

•O

rigin

in t

he

sin

us n

od

e:

pacemaker

•A

tria

l-ve

ntr

icula

r cond

uctio

n

•C

om

ple

te E

CG

•D

isord

ers

of

pacemaker,

conduction, ion

channel

abnormalities

Taken fro

m h

ttp://m

ed.m

c.n

tu.e

du.tw

/~chenhs/c

vd/

Ele

ctr

ocard

iogra

m (

EC

G)

•M

easure

s a

ctivity o

f th

e h

eart

•S

ourc

e o

f card

iac a

ctivity: dip

ole

mode

l

–E

lectr

ical circuit r

epre

senta

tion: equiv

ale

nt genera

tor

•M

easure

ments

on b

ody s

urf

ace o

r in

tracard

iac

–P

ut ele

ctr

odes o

n the tors

o, arm

s, le

gs; cath

ete

r in

sid

e the h

eart

Card

iac v

ecto

r

-has m

agnitude

and d

irection

=>

Dip

ole

(ele

ctr

ical vecto

r

with m

agnitude

and d

irection to

the s

ourc

e)

+

-

Dip

ole

Model

•D

ipo

le r

ep

rese

nts

ele

ctr

ic a

ctivity o

f th

e h

ea

rt

•C

ha

ng

es in

th

e d

ipo

le m

ag

nitu

de

an

d o

rie

nta

tio

n

ca

use

de

tecta

ble

ch

an

ge

s in

th

e e

lectr

ic f

ield

Vecto

r A

lgebra

•D

ot

pro

duct of vecto

rs, w

here

va1

is a

scala

r voltag

e:

•W

hen t

he v

ecto

r is

perp

en

dic

ula

r to

M, v

a1

is z

ero

θcos

11

Ma

M=

⋅=

av

Ein

thoven’s

Triangle

•T

hre

e v

ecto

rs

use

d t

o fu

lly

ide

ntify

the

e

lectr

ica

l a

ctivity

–V

ecto

r show

n in

fronta

l pla

ne o

f th

e b

ody

•K

irch

ho

ff’s

law

is

use

d f

or

the

th

ree

le

ad

s

I –

II +

III

= 0

Ele

ctr

ode P

lacem

ent

Thre

e A

ugm

ente

d L

imb L

ea

ds

Tra

nsvers

e P

lane E

CG

•C

hest

lead

s u

sed t

o o

bta

in t

he E

CG

in t

he tra

nsvers

e

pla

ne

•O

bta

ins E

CG

fro

m the p

oste

rior

sid

e o

f th

e h

eart

Abnorm

al R

hyth

ms o

f th

e H

eart

•N

orm

al sin

us r

hyth

m

•C

ond

uctio

n

abn

orm

alit

ies

•A

tria

larr

hyth

mia

s

•R

ole

of

dia

gnostic/

thera

pe

utic d

evic

es

–P

acem

akers

, exte

rnal

vs. im

pla

nte

d

–P

acem

akers

:

stim

ula

te, corr

ect

conduction

abnorm

alit

ies

Abnorm

al R

hyth

ms o

f th

e H

eart

•P

VC

sare

pre

mon

itory

V

entr

icu

lar

•V

entr

icu

lar

arr

hyth

mia

s a

re

more

leth

al

•R

ole

of

dia

gnostic

monitori

ng in C

CU

•R

ole

of

thera

pe

utic

devic

es

(im

pla

nta

ble

card

iovert

er)

Atr

ial ta

chyca

rdia

Ventr

icula

r ta

ch

ycard

ia

Abnorm

al R

hyth

ms o

f th

e H

eart

•V

entr

icu

lar

Fib

rilla

tio

n is life

thre

ath

en

ing

–R

ole

of

defibrilla

tor:

exte

rnal and

impla

nte

d

•Is

chem

ic h

eart

die

ases

–R

ole

of

monitoring h

eart

dis

ease

Ele

ctr

ore

tinogra

m(E

RG

)

•B

iopote

ntia

lof th

e

eye (

retina)

•In

dic

ato

r of

retinal

dis

eases s

uch a

s

retina

l deg

enra

tio

n,

macula

r

deg

ern

atio

n

•In

vasiv

e r

ecord

ing

•R

etina

l pro

sth

esis

?

Ele

ctr

oencephalo

gra

m (

EE

G)

•A

vera

ged e

lectr

ica

l activity o

f th

e b

rain

cells

(100 b

illio

n!)

•S

yna

ptic

pote

ntia

ls:

pyra

mid

al neuro

n

str

uctu

re f

orm

s a

dip

ole

•R

ecord

ing f

rom

the

scalp

, fr

om

the

cort

ex s

urf

ace

(epile

psy),

intr

a-

cort

ex (

researc

h)

dip

ole

Avera

ged a

ctivity o

f

10e8 n

euro

ns

is v

ery

com

ple

x: in

dic

ative o

f

-sle

ep s

tage

-epile

psy

-event

rela

ted

changes

-b

rain

-com

pute

r

inte

rface???

Cere

bra

l A

nato

my Neurophysiology

of brain/cortex

-G

ross

org

an

izatio

n:

left

/rig

ht,

diffe

rent

lobs

-F

iner:

gyri a

nd

sulc

i (f

issure

s)

-La

yer

str

uctu

re (

6

layers

of

diffe

rent

types o

f ne

uro

ns

-H

om

uncu

lus:

rough o

rgan

iza

tion

of

sensory

are

as

alo

ng t

he s

ensory

-

moto

r cort

ex

Rhyth

ms o

f th

e B

rain

Different brain waves: divided by spectral

differences: 0—4 (delta), 4-8 (theta), 8-12

(alpha), 12 up (beta): delta/theta in infants,

disease; alpha: sleep; beta: awake, eyes

open

EEG in brain diesease and disorders:

Epilepsy –different types and forms

Brain injury –definition of death?

EE

G E

lectr

od

e R

ecord

ing S

yste

m

•E

EG

record

ing is

don

e u

sin

g a

sta

ndard

le

ad

syste

m c

alle

d 1

0-

20 s

yste

m

•R

ecall

dip

ole

conce

pt to

id

entify

sourc

e o

f bra

in a

ctivity

•In

tere

st in

m

app

ing s

leep

sta

ges,

site o

f seiz

ure

, and

cort

ical fu

nction

Pro

gre

ssio

n o

f E

EG

duri

ng S

leep

Clinical uses of EEG

-Sleep staging: note

different features

-e.g. REM (rapid eye

movement stage)

-Monitoring in

neurocritical care

-e.g. live/dead, coma

status

-Intraoperative monitoring

for depth of anesthesia

-e.g. changes with

anesthesia and depth

status

Refe

rence

•W

ebste

r, J

G (

1998).

M

edic

al

Instr

um

enta

tion. J

ohn W

iley &

Sons, In

c.,

New

York

, N

Y. C

hapte

r 4.

Pro

ble

ms a

nd s

elf-s

tudy

1 A

) H

odgkin

and H

uxle

y r

ece

ived a

No

bel pri

ze f

or

their w

ork

with S

quid

axo

n

to d

ecip

her

the

role

of

ion c

ha

nnels

and f

orm

ation o

f action p

ote

ntia

l.

Researc

h o

rig

inal pa

pers

an

d a

) pre

sent

gra

phic

s o

f th

eir r

ecord

ing t

echn

ique,

b)

describ

e t

he

voltage c

lam

p m

eth

od a

nd its

use,

c)

option

ally

:re

searc

h a

nd

pre

sent/

descri

be t

he v

oltag

e c

lam

p c

ircu

it

B)

Bert

Sakm

an

and E

rwin

Neher

rece

ived a

Nobe

l prize f

or

their d

eve

lopm

ent

of

a p

atc

h p

ipe

tte e

lectr

ode r

ecord

ing t

echniq

ue f

or

measure

ment

of

ion

chann

el activity.

Sho

w t

he s

chem

atic o

f a p

atc

h p

ipett

e a

ttached t

o a

) cell

and

b)

mem

bra

ne.

In e

ach c

ase,

wh

at

is t

he s

ou

rce o

f th

e c

urr

ent

bein

g

measure

d? O

ptionally

desig

n t

he p

atc

h c

lam

p c

ircuit.

C)

Dra

w t

he d

iffe

rent

ion c

ha

nnels

an

d c

urr

ents

active d

urin

g a

card

iac a

ction

pote

ntia

l. R

ese

arc

h h

ow

pace

maker

pote

ntia

l arizes (

rep

ola

rization o

f th

e

action p

ote

ntial)

, and h

ow

isch

em

ia m

ight

alte

r th

e a

ction p

ote

ntials

Atrial

signal

Ventricular

signal

3. A) You are asked to develop an experimental set up to record from rat brain cells

using microelectrodes. What precautions would you take to minimize the electrical

interference in your recording set up?

3. B) You are asked to record magnetic field from the brain. Now, brain’s magnetic field

is 10e-15 Tesla as opposed to earth’s field which is 10e-7 Tesla. What kind of sensor

would you use to record brain’s magnetic field (now, I realize that this is a long shot –

but just may be, you could figure this out)? What precautions would you take to

record this very small magnetic field from the brain in presenceof other interference?

Also, show the

pacing pulse at the

appropriate time

instant in theAtrial

and Ventricular

signals on the left.

2. A) The goal of the pacemaker is to provide an electrical pacing pulse when the

appropriate chamber of the heart is not spontaneously or sequentially not beating.

2. B) For the following recording situation, identify where you would put a

“sensing”electrode, a “pacing”electrode and what the timing of the pacing pulse

would be. That is, show the electrode (catheter) in a schematicof the heart.

4. A) What does the 12-lead ECG system comprise of (sketch the different leads)?

Is it superior or inferior to an orthogonal system (X, Y, and Z leads)? the different

leads)? Is it superior or inferior to an orthogonal system (X, Y, and Z leads)?

B) The ECG signal generating from the heart can be 6.2A) What does the 12-

lead ECG system comprise of (sketch modeled quite simply as a dipole. If a cardiac

dipole has a magnitude of 1 mV and orientation of –45owith respect to Lead I, then

calculate, using theEinthoventriangle, the magnitude of the signal in Lead I, II, and III.

Show the geometric presentation as well as the trigonometric calculations.

5. A) Imagine it is the beginning of the 20thcentury. Cardiac activity is suspected as

an electrical source inside the torso. Let us say that you were a contemporary of Prof.

Einthoven. Prof.Einthovenrecommends that to record ECG from the torso using a

triangular formulation with what you now know at three leads, I,II, and III (respectively

LA-RA, RA-LL, and LA-LL). However, you claim have a different theory of better

presenting the cardiac vector on a different lead system (for example, you prefer not

to use 3 leads arranged in the form of a triangle). Demonstrate superiority of your lead

idea. B) After Einthoven’soriginal idea, a number of solutions were suggested. One of

these was to put 6 leads (V1-V6) around the left ventricle. a) why around left

ventricle? b) for the 6 differential amplifiers, each with one input being V1..V6 what is

the other “neutral”input source?

6. A) Explain the origin of EEG signal in terms of its sources in the brain. Describe

briefly the neural generator and the electrical field/vector representation that

explains how an internal source produces an external EEG.

B) What are the advantages and disadvantages of putting EEG electrodes on the

scalp versus directly on the brain? Under what clinical condition is either

procedure recommended? What kinds of electrodes are used for direct cortical

recording? What are the design considerations? How does a neurologist identify

an epileptic spike or seizure? How does a surgeon determine where to “cut”the

brain to remove the focus?

C) What kind of a lead system would you use to record EEG from the scalp and for

localizing the source of epileptic seizure? Sketch it. Now, putting electrodes on

the scalp may not help localize the seizure focus better. Surgeons now put

electrodes directly on brain. Research direct cortical recordingof seizure and

describe/Illustrate the technology.

D) i) What instrument is used to measure the magnetic field fromthe brain?

ii) What are the possible advantages and disadvantages of the magnetic versus

electrical measurement? iii) To your knowledge, what breakthroughs in the

scientific world that have are occurred (or ought to occur?) that would make

magnetic field measurement more feasible and affordable? iv) If you had a cheap

magnetic field sensor (with a relatively lower sensitivity) available what other

biomedical application would you think of (other thanbiopotentialmeasurements).

7. A) We would like to record ECG of a fetus while in the womb.The main problem

here is that when electrodes are placed on the mother’s stomach to capture the fetal

ECG, a large maternal ECG signal pulse is also picked up. A) Draw a schematic of the

mother and her heart dipole/vector and fetus and its heart dipole/vector. Now, show

how mother’s ECG might corrupt the fetal ECG. B) How would you eliminate the

maternal ECG artifact from the stomach recording? C) Someone suggests that at the

most critical moment in labor, as the head of the fetus presentsitself first , attach the

ECG electrode to fetal scalp. Would you succeed or not in getting fetal ECG from an

electrode placed on the scalp and why/why not? D) During the time of the late stage

labor, what would be more likely to succeed –electrodes on the mother’s stomach or

an electrode on fetus’s head?

B) Show (draw) the possible current distribution between anelectrosurgicalelectrode,

body and the return ground electrode. What would be the desirable properties of the

ground reference electrode?

C) Students in the past have proposed two methods for monitoringeye movements as

a way to provide a command/control signal for a quadriplegic (e.g. eye movement

command may be used to move a cursor on the computer screen). What might be two

such methods (Hint: one is optical and other is based on biopotentials)?

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