Lecture 2

Chapter 4: The Origin of

Biopotentials

Dr. Nitish V. Thakor

Biomedical Instrumentation
JHU Applied Physics Lab
 Introduction
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:
3. Action Potentials from Cells (and 3 Nobel prizes!)
• Neuronal action potential (history of Squid axon and Hodgkin-Huxley work)
• Patch clamp technique and single channel recording (Sakman-Neher)
• Water channel work of Peter Agre (JHU)
4. 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…
Electrical Activity of Excitable Cells
Neuronal action potential

• Excitable cells 0 mV
repolarization:
– Exist in nervous, muscular K+ outflux
and glandular tissue
- 70 mV
– Exhibit a resting potential
and an action potential depolarization:
– Necessary for information Na+ influx

transfer (e.g. sensory info Cardiac action potential

in nervous system or repolarization:
K+ outflux
coordination of blood
pumping in the heart)

Na+ Ca++ K+
 Resting vs. Active State
• Resting State
– Steady electrical potential of difference
between 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 Membrane Potential
• Cell potential is a function of membrane permeability and
concentration gradient to various molecules (i.e. K+, Na+,
Cl-, and Ca2+)
• Equilibrium potential is the membrane potential at which
a given molecule has no net movement across the
membrane
– Nernst Equation (in Volts at 37 oC):
RT [ K ]o [ K ]o
EK = ln = 0.0615 log10
nF [ K ]i [ K ]i
– n is the valence of K+, [K]i and [K]o are the intra- and extracellular
concentrations, R is the universal gas constant, T is the absolute
temperature in Kelvin, F is the Faraday constant, and EK is the
equilibrium potential
 Resting Membrane Potential
• Equilibrium membrane resting potential when
net current through the membrane is zero
RT  PK [ K ]o + PNa [ Na ]o + PCl [Cl ]i 
E= ln  
F  PK [ K ]i + PNa [ Na ]i + PCl [Cl ]o 
– P is the permeability coefficient of the given ion
• Factors influencing ion flow across the
membrane
– Diffusion gradients
– Inwardly-directed electric field
– Membrane structure
– Active transport of ions against electrochemical
gradient
 Action Potential
• Stimulation of excitable cells causes “all-or-
none” response
• At threshold, the membrane potential rapidly
depolarizes due to a change in membrane
permeability
– PNa significantly increases causing the membrane
potential to approach ENa (+60mV)
• A delayed increase in PK causes
hyperpolarization and a return to resting
potential
Action Potential and Ionic
Conductance
• gNa and gK are
the
conductance of
Na+ and K+
• v is the
membrane
potential
• Absolute and
relative
refractory
periods
 Circuit Diagram of Membrane

• Network equivalent circuit of a small increment of

membrane
• Note critical elements: extracellular-intracelluar
– Membrane capacitance, voltage dependent ion channel
conductance, reverse potential for each ion channel (Na, K, …)
 Neuron Schematic
• Conduction along
a nerve
– Result of
depolarization of
small patch of
membrane
– Conduction
along a nerve
fiber (more
generally axons
and dendrites)
– Saltatory
conduction along
myelinated fibers
in nerves, spinal
cord
Organization of Peripheral Nervous
System
• Reflex arc
– Sense organ (e.g. receptors)
– Sensory nerve (transfers information from receptor to
CNS)
– CNS (i.e. information processing station)
– Motor nerve (transfers information from CNS to
effector organ)
– Effector Organ (i.e. muscles)
• Simplest example
– Knee reflex
Reflex Arc
Organization of Peripheral Nervous
System
• Junctional Transmission
– Communication links between
• Neurons and neuron conntections: called synapses
• Neurons and effector organs, called end-plate region
– Electrochemical transmission via neurotransmitters:
(Inhibitory and Excitatory; chemical, gaseous)
• Acetylcholine Postsynaptic channel
• GABA opening and membrane
depolarization
• Glutamate
• Dopamine
• Nitric oxide Transmission of action
potential
Presynaptic release of
neurotransmitter
 Electroneurogram (ENG)
• Measures nerve field
potentials
• Use of needle electrodes
• Stimulate the peripheray
and measure the
conduction velocity
• Used in assessing
neuromuscular disorders:
peripheral nerve injury,
muscular dystrophy
Electromyogram (EMG)
• Measures muscle
activity
• Record
intramuscularly
through needle
electrodes
• Record surface
EMG using
electrodes on
biceps, triceps…
• Use in muscular
disorders, muscle
based prosthesis –
prosthetic arm, leg
 Anatomy of the Heart

http://info.med.yale.edu/intmed/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://med.mc.ntu.edu.tw/~chenhs/cvd/
 Electrocardiogram (ECG)
Cardiac vector
-has magnitude
+
and direction
=> Dipole
(electrical vector -
with magnitude
and direction to
the source)

• Measures activity of the heart

• Source of cardiac activity: dipole model
– Electrical circuit representation: equivalent generator
• Measurements on body surface or intracardiac
– Put electrodes on the torso, arms, legs; catheter inside the heart
 Dipole Model
• Dipole represents electric activity of the heart
• Changes in the dipole magnitude and orientation
cause detectable changes in the electric field
 Vector Algebra

• Dot product of vectors, where va1 is a scalar voltage:

v a1 = M ⋅ a1 = M cos θ
• When the vector is perpendicular to M, va1 is zero
Einthoven’s Triangle
• Three vectors
used to fully
identify the
electrical activity
– Vector shown in
frontal plane of
the body
• Kirchhoff’s law is
used for the
three leads
I – II + III = 0
Electrode Placement
Three Augmented Limb Leads
 Transverse Plane ECG

• Chest leads used to obtain the ECG in the transverse

plane
• Obtains ECG from the posterior side of the heart
 Abnormal Rhythms of the Heart
• Normal sinus rhythm
• Conduction
abnormalities
• Atrial arrhythmias
• Role of diagnostic/
therapeutic devices
– Pacemakers, external
vs. implanted
– Pacemakers:
stimulate, correct
conduction
abnormalities
Abnormal Rhythms of the Heart
• PVCs are
premonitory
Ventricular
• Ventricular
arrhythmias are
more lethal
• Role of diagnostic
monitoring in CCU Ventricular tachycardia
• Role of
therapeutic
devices Atrial tachycardia
(implantable
cardioverter)
Abnormal Rhythms of the Heart
• Ventricular
Fibrillation is life
threathening
– Role of
defibrillator:
external and
implanted
• Ischemic heart
dieases
– Role of
monitoring heart
disease
 Electroretinogram (ERG)
• Biopotential of the
eye (retina)
• Indicator of retinal
diseases such as
retinal degenration,
macular
degernation
• Invasive recording
• Retinal prosthesis?
 Electroencephalogram (EEG)
Averaged activity of
10e8 neurons is very
• Averaged electrical
complex: indicative of activity of the brain
- sleep stage cells (100 billion!)
- epilepsy • Synaptic
- event related potentials:
changes pyramidal neuron
- brain-computer structure forms a
interface??? dipole
dipole • Recording from the
scalp, from the
cortex surface
(epilepsy), intra-
cortex (research)
Cerebral Anatomy
Neurophysiology
of brain/cortex
- Gross
organization:
left/right, different
lobs
- Finer: gyri and
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 EEG in brain diesease and disorders:
differences: 0—4 (delta), 4-8 (theta), 8-12
Epilepsy – different types and forms
(alpha), 12 up (beta): delta/theta in infants,
disease; alpha: sleep; beta: awake, eyes Brain injury – definition of death?
open
 EEG Electrode Recording System
• EEG recording is
done using a
standard lead
system called 10-
20 system
• Recall dipole
concept to
identify source of
brain activity
• Interest in
mapping 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
- Intraoperative monitoring
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) Hodgkin and Huxley received a Nobel prize for their work with Squid axon
to decipher the role of ion channels and formation of action potential.
Research original papers and a) present graphics of their recording technique,
b) describe the voltage clamp method and its use, c) optionally: research and
present/describe the voltage clamp circuit

B) Bert Sakman and Erwin Neher received a Nobel prize for their development
of a patch pipette electrode recording technique for measurement of ion
channel activity. Show the schematic of a patch pipette attached to a) cell and
b) membrane. In each case, what is the source of the current being
measured? Optionally design the patch clamp circuit.

C) Draw the different ion channels and currents active during a cardiac action
potential. Research how pacemaker potential arizes (repolarization of the
action potential), and how ischemia might alter the action potentials
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 schematic of the heart.

Also, show the

pacing pulse at the
Atrial appropriate time
signal instant in the Atrial
and Ventricular
signals on the left.
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 presence of other interference?
 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 6.2 A) 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 –45o with respect to Lead I, then calculate,
using the Einthoven triangle, 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 20th century. Cardiac activity is suspected as an

electrical source inside the torso. Let us say that you were a contemporary of Prof.
Einthoven. Prof. Einthoven recommends 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’s original 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 recording of seizure and
describe/Illustrate the technology.

D) i) What instrument is used to measure the magnetic field from the 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 than biopotential measurements).
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 presents itself 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 an electrosurgical electrode,

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 monitoring eye 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)?
 Body Power!!!
• Power for an implanted stimulator (BION)
– Battery, induction (radio frequency)
– Heat, chemical, flow, mechanical, …
• What is your energy transduction principle
– What sensor/actuator would you use
– What circuit principle? E.g. piezo->electricity to power
the stimulator
– What physical/chemical/ electrochem/optical principle?
– What’s wrong/bad about this (e.g. effluent, gas, …)
– What kind of energy density you can obtain? What is
the conversion efficiency of each of these?
• Real world examples, patents, products
 More questions
• How many electrodes/lead in a 12 lead system?
• What are the sources of interference in
biopotential recording?
• How do you increase the likelihood of recording
event-related potential? How do you increase
the signal-to-noise ratio? (averaging)
• Research and describe neurochemical sensor
technologies