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
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
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)?