Lecture 4

Chapter 4: The O

rigin of

Biopotentials

Dr. Nitish V. Thakor

Biomedical Instrumentation

JHU Applied Physics Lab

Introduction

Biopotentialsarise 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. Biopotentialsfrom 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.Biopotentialsfrom 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…

Electrical Activity of Excitable Cells

•Excitable cells

–Exist in nervous, muscular

and glandular tissue

–Exhibit a resting potential

and an action potential

–Necessary for inform

ation

transfer (e.g. sensory info

in nervous system or

coordination of blood

pumping in the heart)

0 m

V

-70 m

V

depolarization:

Na+ influx

repolarization:

K+ outflux

Na+ Ca++ K+

Neuronal action potential

Cardiac action potential

Resting vs. Active State

•Resting State

–Steady electrical potential of difference betw

een

internal and external environments

–Typically between -70 to -90mV, relative to the

external medium

•Active State

–Electrical response to adequate stimulation

–Consists of “all-or-none”action potential after the cell

threshold potential has been reached

Recording of Action Potential

•Typical recording

system (top) using

microelectrode

•Recording of an

action potential in

nerve cell

(bottom)

Resting M

embrane Potential

•Cell potential is a function of membrane perm

eability and

concentration gradient to various m

olecules (i.e. K

+, Na+,

Cl- , and C

a2+)

•Equilibrium potential is the m

embrane potential at which

a given m

olecule has no net movement across the

membrane

–NernstEquation (in Volts at 37 oC):

–nis the valence of K

+, [K] iand [K] oare the intra-and extracellular

concentrations, Ris the universal gas constant, T is the absolute

temperature in Kelvin, Fis the Faraday constant, and EKis the

equilibrium potential

io

io

K

KK

KK

nF

RT

E]

[

][

log

0615

.0

][

][

ln10

==

Resting M

embrane Potential

•Equilibrium m

embrane resting potential when net current

through the m

embrane is zero

–Pis the perm

eability coefficient of the given ion

•Factors influencing ion flow across the m

embrane

–Diffusion gradients

–Inwardly-directed electric field

–Membrane structure

–Active transport of ions against electrochemical gradient

++

++

=o

Cl

iNa

iK

iCl

oNa

oK

Cl

PNa

PK

P

Cl

PNa

PK

P

FRT

E]

[]

[]

[

][

][

][

ln

Action Potential

•Stimulation of excitable cells causes “all-or-none”

response

•At threshold, the m

embrane potential rapidly depolarizes

due to a change in m

embrane perm

eability

–P

Nasignificantly increases causing the m

embrane potential to

approach E

Na(+60mV)

•A delayed increase in P

Kcauses hyperpolarizationand a

return to resting potential

Action Potential and Ionic

Conductance

•gNaand g

Kare the

conductance of Na+

and K

+

•vis the m

embrane

potential

•Absolute and

relative refractory

periods

Circuit Diagram of Membrane

•Netw

ork equivalent circuit of a small increment of

membrane

•Note critical elements: extracellu

lar-intracellu

ar

–Membrane capacitance, voltage dependent ion channel

conductance, reverse potential for each ion channel (N

a, K, …)

Neuron Schematic

•Conduction along a

nerve

–result of depolarization

of small patch of

membrane

–conduction along a

nerve fiber (m

ore

generally axons and

dendrites)

–saltatory

conduction

along m

yelinatedfibers

in nerves, spinal cord

Organization of Peripheral

Nervous System

•Reflex arc

–Sense organ (e.g. receptors)

–Sensory nerve (transfers info from receptor to CNS)

–CNS (i.e. inform

ation processing station)

–Motor nerve (transfers inform

ation from CNS to

effectororgan)

–EffectorOrgan (i.e. muscles)

•Sim

plest example

–Knee reflex

Reflex Arc

Organization of Peripheral

Nervous System

•JunctionalTransmission

–Communication links between

•Neurons and neuron conntections: called synapses

•Neurons and effectororgans, called end-plate region

–Electrochemical transmission via neurotransmitters:

(Inhibitory and Excitatory; chemical, gaseous)

•Acetylcholine

•GABA

•Glutamate

•Dopamine

•Nitric oxide P

resynapticrelease of

neurotransmitter

Postsynaptic channel

opening and m

embrane

depolarization

Transmission of action

potential

Electroneurogram

(ENG)

•Measures nerve field

potentials

•Use of needle electrodes

•Stimulate the peripheray

and m

easure the

conduction velocity

•Used in assessing

neuromuscular disorders:

peripheral nerve injury,

muscular dystrophy

Electromyogram

(EMG)

•Measures m

uscle

activity

•Record intramuscularly

through needle

electrodes

•Record surface EMG

using electrodes on

biceps, triceps…

•Use in m

uscular

disorders, muscle

based prosthesis –

prosthetic arm

, leg

Anatomy of the Heart

http://info.m

ed.yale.edu/intm

ed/cardio/echo_atlas/references/graphics/heart_anatomy.gif

Electrical Behavior of the Heart

•Conduction

system

•Origin in the sinus

node: pacemaker

•Atrial-ventricular

conduction

•Complete ECG

•Disorders of

pacemaker,

conduction, ion

channel

abnormalities

Taken from http://m

ed.m

c.ntu.edu.tw/~chenhs/cvd/

Electrocardiogram (ECG)

•Measures activity of the heart

•Source of cardiac activity: dipole m

odel

–Electrical circuit representation: equivalent generator

•Measurements on body surface or intracardiac

–Put electrodes on the torso, arm

s, legs; catheter inside the heart

Dipole M

odel

•Dipole represents electric activity of the heart

•Changes in the dipole m

agnitude and orientation cause

detectable changes in the electric field

Vector Algebra

•Dot product of vectors, where v

a1is a scalar voltage:

•When the vector is perpendicular to M

, va1is zero

θco

s1

1M

aM

=⋅

=av

Einthoven’sTriangle

•Three vectors used to

fully identify the

electrical activity

–vector shown in frontal

plane of the body

•Kirchhoff’slaw is used

for the three leads

I –II + III = 0

Electrode Placement

Three Augmented Lim

b Leads

Transverse Plane ECG

•Chest leads used to obtain the ECG in the transverse

plane

•Obtains ECG from the posterior side of the heart

Abnorm

al Rhythms of the Heart

•Norm

al sinus rhythm

•Conduction

abnorm

alities

•Atrialarrhythmias

•Role of diagnostic/

therapeutic devices

–Pacemakers, external

vs. im

planted

–Pacemakers:

stimulate, correct

conduction

abnorm

alities

Abnorm

al Rhythms of the Heart

•PVCsare premonitory

Ventricular

•Ventricular arrhythmias

are m

ore lethal

•Role of diagnostic

monitoring in C

CU

•Role of therapeutic

devices (im

plantable

cardioverter)

Abnorm

al Rhythms of the Heart

•Ventricular

Fibrilla

tion is life

threathening

–Role of defibrillator:

external and

implanted

•Ischemic heart

dieases

–Role of monitoring

heart disease

Electroretinogram

(ERG)

•Biopotentialof the

eye (retina)

•Indicator of retinal

diseases such as

macular

degernation

•Invasive recording

•Retinal prosthesis?

Electroencephalogram (EEG)

•Averaged electrical

activity of the brain

cells (100 billion!)

•Synaptic potentials:

pyramidal neuron

structure form

s a

dipole

•Recording from the

scalp, from the

cortex surface

(epile

psy), intra-

cortex (research)

dipole

Averaged activity of

10e8 neurons is very

complex: indicative of

-sleep stage

-epile

psy

-event related

changes

-brain-computer

interface???

Cerebral Anatomy

Neurophysiology of

brain/cortex

-Gross organization:

left/right, different lobs

-Finer: gyriand sulci

(fissures)

-Layer structure (6 layers

of different types of

neurons

-Homunculus: rough

organization of sensory

areas along the sensory-

motor cortex

Rhythms of the Brain

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 dieseaseand disorders:

Epilepsy –different types and forms

Brain injury –definition of death?

EEG Electrode Recording System

•EEG recording is

done using a

standard lead system

calle

d 10-20 system

•Recall dipole concept

to identify source of

brain activity

•Interest in m

apping

sleep stages, site of

seizure, and cortical

function

Progression of EEG during Sleep

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

-Intraoperativemonitoring for

depth of anesthesia

e.g. changes with

anesthesia and depth status

Reference

•Webster, JG (1998). Medical Instrumentation. John

Wiley & Sons, Inc., New York, NY. Chapter 4.

Problems and Self-study

1 A

) H

odgkin

and H

uxle

y rec

eived

a N

obel

prize

for th

eir w

ork

with S

quid

axon to

dec

ipher

the

role

of io

n c

han

nel

s an

d form

atio

n o

f ac

tion p

ote

ntial

. R

esea

rch o

rigin

al

pap

ers an

d a

) pre

sent gra

phic

s of th

eir re

cord

ing tec

hniq

ue,

b) des

crib

e th

e voltag

e

clam

p m

ethod a

nd its u

se, c)

optional

ly: re

sear

ch a

nd p

rese

nt/des

crib

e th

e voltag

e

clam

p c

ircu

it

B) Ber

t Sak

man

and E

rwin

Neh

erre

ceiv

ed a

Nobel

prize

for th

eir dev

elopm

ent of a

pat

ch p

ipet

te e

lect

rode

reco

rdin

g tec

hniq

ue

for m

easu

rem

ent of io

n c

han

nel

act

ivity.

Show

the

schem

atic

of a

pat

ch p

ipet

te a

ttac

hed

to a

) ce

ll a

nd b

)m

embra

ne.

In

eac

h

case

, w

hat

is th

e so

urc

e of th

e cu

rren

t bei

ng m

easu

red?

Optional

ly d

esig

n the

pat

ch

clam

p c

ircu

it.

C) D

raw

the

diffe

rent io

n c

han

nel

s an

d c

urren

ts a

ctiv

e during a

car

dia

c ac

tion

pote

ntial

. Res

earc

h h

ow

pac

emak

er p

ote

ntial

arize

s(rep

ola

riza

tion

of th

e ac

tion

pote

ntial

), a

nd h

ow

isc

hem

ia m

ight al

ter th

e ac

tion p

ote

ntial

s

Atria

l

signal

Ven

tric

ula

r

signal

3. A

) Y

ou a

re a

sked

to d

evel

op a

n e

xper

imen

tal se

t up to rec

ord

fro

m rat

bra

in c

ells u

sing

mic

roel

ectrodes

. W

hat

pre

cautions w

ould

you tak

e to

min

imiz

e th

e el

ectric

al inte

rfer

ence

in y

our re

cord

ing set

up?

B) Y

ou a

re a

sked

to rec

ord

mag

net

ic fie

ld fro

m the

bra

in. N

ow

, bra

in’s

mag

net

ic fie

ld is

10e-

15 T

esla

as oppose

d to e

arth

’s fie

ld w

hic

h is 10e-

7 T

esla

. W

hat

kin

d o

f se

nso

r w

ould

you u

se to rec

ord

bra

in’s

mag

net

ic fie

ld (now

, I re

aliz

e th

at this is a

long shot –

but ju

st

may

be,

you c

ould

fig

ure

this o

ut)?

What

pre

cautions w

ould

you tak

e to

rec

ord

this v

ery

smal

l m

agnet

ic fie

ld fro

m the

bra

in in p

rese

nce

of oth

er inte

rfer

ence

?

Also, sh

ow

the

pac

ing

pulse

at the

appro

priat

e tim

e

instan

t in

the

Atria

l

and V

entric

ula

r

signal

s on the

left.

2. A

) The

goal

of th

e pac

emak

er is to

pro

vid

e an

ele

ctrica

l pac

ing p

ulse

when

the

appro

priat

e ch

amber

of th

e hea

rt is not sp

onta

neo

usly o

r se

quen

tial

ly n

ot bea

ting.

B) For th

e fo

llow

ing rec

ord

ing situat

ion, id

entify

wher

e you w

ould

put a

“sen

sing”

elec

trode,

a “

pac

ing”

elec

trode

and w

hat

the

tim

ing o

f th

e pac

ing p

ulse

would

be.

That

is, sh

ow

the

elec

trode

(cat

het

er) in

a sch

emat

ic o

f th

e hea

rt.

4. A

) W

hat

does

the

12-lea

d E

CG

system

com

prise

of (s

ket

ch the

diffe

rent le

ads)

? Is it

super

ior or in

ferior to

an o

rthogonal

system

(X

, Y

, an

d Z

lea

ds)

? th

e diffe

rent le

ads)

? Is it

super

ior or in

ferior to

an o

rthogonal

system

(X

, Y

, an

d Z

lea

ds)

?

B) The

ECG

sig

nal

gen

erat

ing fro

m the

hea

rt c

an b

e 6.2

A) W

hat

does

the

12-lea

d E

CG

system

com

prise

of (s

ket

ch m

odel

ed q

uite

sim

ply

as a

dip

ole

. Ifa

card

iac

dip

ole

has

a

mag

nitude

of 1 m

V a

nd o

rien

tation o

f –45

ow

ith res

pec

t to

Lea

d I, th

en c

alcu

late

, using the

Ein

thoven

tria

ngle

, th

e m

agnitude

of th

e signal

in L

ead I, II, an

d III. S

how

the

geo

met

ric

pre

senta

tion a

s w

ell as

the

trig

onom

etric

calc

ula

tions.

5. A

) Im

agin

e it is th

e beg

innin

g o

f th

e 20

thce

ntu

ry. C

ardia

c ac

tivity is su

spec

ted a

s an

elec

tric

al sourc

e in

side

the

tors

o. Let

us sa

y that

you w

ere

a co

nte

mpora

ry o

f Pro

f.

Ein

thoven

. P

rof. E

inth

oven

reco

mm

ends th

at to rec

ord

ECG

fro

m the

tors

o u

sing a

tria

ngula

r fo

rmula

tion w

ith w

hat

you n

ow

know

at th

ree

lead

s, I,II, an

d III (re

spec

tivel

y

LA

-RA

, RA

-LL, an

d L

A-L

L). H

ow

ever

, you c

laim

hav

e a

diffe

rent th

eory

of bet

ter

pre

senting the

card

iac

vec

tor on a

diffe

rent le

ad system

(fo

r ex

ample

, you p

refe

r not to

use

3 lea

ds ar

ranged

in the

form

of a

tria

ngle

). D

emonstra

te super

iority

of your le

ad idea

.

B) A

fter

Ein

thoven

’sorigin

al idea

, a

num

ber

of so

lutions w

ere

sugges

ted. O

ne

of th

ese

was

to p

ut 6 lea

ds (V

1-V

6) ar

ound the

left v

entric

le. a

) w

hy a

round lef

t ven

tric

le?

b)fo

r

the

6 d

iffe

rential

am

plifier

s, e

ach w

ith o

ne

input bei

ng V

1..V

6 w

hat

is th

e oth

er “

neu

tral

”

input so

urc

e?

6. A

) Expla

in the

origin

of EEG

sig

nal

in ter

ms of its so

urc

es in the

bra

in. D

escr

ibe

brief

ly the

neu

ral gen

erat

or an

d the

elec

tric

al fie

ld/v

ecto

r re

pre

senta

tion that

expla

ins

how

an inte

rnal

sourc

e pro

duce

s an

exte

rnal

EEG

.

B) W

hat

are

the

advan

tages

and d

isad

van

tages

of puttin

g E

EG

ele

ctro

des

on the

scal

p

ver

sus direc

tly o

n the

bra

in?

Under

what

clinic

al c

onditio

n is ei

ther

pro

cedure

reco

mm

ended

? W

hat

kin

ds of el

ectrodes

are

use

d for direc

t co

rtic

al rec

ord

ing?

What

are

the

des

ign c

onsider

atio

ns?

How

does

a n

euro

logist id

entify

an e

pilep

tic

spik

e or

seiz

ure

? H

ow

does

a surg

eon d

eter

min

e w

her

e to

“cu

t”th

e bra

in to rem

ove

the

focu

s?

C) W

hat

kin

d o

f a

lead

system

would

you u

se to rec

ord

EEG

fro

m the

scal

p a

nd for

loca

lizi

ng the

sourc

e of ep

ilep

tic

seiz

ure

? S

ket

ch it. N

ow

, puttin

g e

lect

rodes

on the

scal

p m

ay n

ot hel

p loca

lize

the

seiz

ure

focu

s bet

ter. S

urg

eons now

put el

ectrodes

direc

tly o

n b

rain

. Res

earc

h d

irec

t co

rtic

al rec

ord

ing o

f se

izure

and d

escr

ibe/

Illu

stra

te the

tech

nolo

gy.

D) i) W

hat

instru

men

t is u

sed to m

easu

re the

mag

net

ic fie

ld fro

mth

e bra

in?

ii) W

hat

are

the

poss

ible

advan

tages

and d

isad

van

tages

of th

e m

agnet

ic v

ersu

s el

ectric

al

mea

sure

men

t? iii) T

o y

our know

ledge,

what

bre

akth

roughs in

the

scie

ntific

world that

hav

e ar

e occ

urred

(or ought to

occ

ur?

) th

at w

ould

mak

e m

agnet

ic fie

ld m

easu

rem

ent

more

fea

sible

and a

fford

able

? iv

) If y

ou h

ad a

chea

p m

agnet

ic fie

ld sen

sor (w

ith a

rela

tivel

y low

er sen

sitivity) av

aila

ble

what

oth

er b

iom

edic

al a

pplica

tion w

ould

you

thin

k o

f (o

ther

than

bio

pote

ntial

mea

sure

men

ts).

7. A

) W

e w

ould

lik

e to

rec

ord

ECG

of a

fetu

s w

hile

in the

wom

b.

The

mai

n p

roble

m h

ere

is that

when

ele

ctro

des

are

pla

ced o

n the

moth

er’s

sto

mac

h to c

aptu

re the

feta

l ECG

, a

larg

e

mat

ernal

ECG

sig

nal

pulse

is a

lso p

icked

up. A

) D

raw

a sch

emat

icof th

e m

oth

er a

nd h

er

hea

rt d

ipole

/vec

tor an

d fet

us an

d its h

eart d

ipole

/vec

tor. N

ow

,sh

ow

how

moth

er’s

ECG

mig

ht co

rrupt th

e fe

tal ECG

. B

) H

ow

would

you e

lim

inat

e th

e m

ater

nal

ECG

artifac

t from

the

stom

ach rec

ord

ing?

C) Som

eone

sugges

ts that

at th

e m

ost c

ritica

l m

om

ent in

lab

or, a

s

the

hea

d o

f th

e fe

tus pre

sents itsel

f firs

t , at

tach

the

ECG

ele

ctro

de

to fet

al sca

lp. W

ould

you

succ

eed o

r not in

get

ting fet

al E

CG

fro

m a

n e

lect

rode

pla

ced o

n the

scal

p a

nd w

hy/w

hy n

ot?

D) D

uring the

tim

e of th

e la

te sta

ge

labor, w

hat

would

be

more

lik

ely to succ

eed –

elec

trodes

on the

moth

er’s

sto

mac

h o

r an

ele

ctro

de

on fet

us’

s hea

d?

B) S

how

(dra

w) th

e poss

ible

curren

t distrib

ution b

etw

een a

n e

lect

rosu

rgic

al e

lect

rode,

body

and the

retu

rn g

round e

lect

rode.

W

hat

would

be

the

des

irab

le p

roper

ties

of th

e gro

und

refe

rence

ele

ctro

de?

C) Stu

den

ts in the

pas

t hav

e pro

pose

d tw

o m

ethods fo

r m

onitoring

eye

movem

ents a

s a

way

to p

rovid

e a

com

man

d/c

ontrol signal

for a

quad

riple

gic

(e.

g. ey

em

ovem

ent co

mm

and m

ay

be

use

d to m

ove

a cu

rsor on the

com

pute

r sc

reen

). W

hat

mig

ht be

two such

met

hods (H

int:

one

is o

ptica

l an

d o

ther

is bas

ed o

n b

iopote

ntial

s)?