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Summary Biomedical instrumentation for biomedical engineering students at the RUG
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Summary of all content needed to know for the exam of ventilation, audiology, neurology and opthalmology.
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Neurology 128-9-2021
Neurolophysiology
‘Clinical Neuroengineering’ approach.
Clinical neurological problem try to translate into a more engineering problem / physical-
mathematical problem find a solution for the physical-mathematical-engineering problem put
this back into practice for the neurological problem.
Case of epilepsy symptoms:
- Episodes of absent mindedness: stop talking, eyes turning away.
- Several times a day, lasting a couple of seconds.
- Patient forgot what he was doing.
- Episode was induced by hyperventilation.
An example of such an absence epilepsy attack is a seizure. Seizures can have different causes:
- Syncope (=fainting)
- Functional (=no well known reason for the seizure)
- Epilepsy
o Epileptic seizure come in many types. This results from the part(s) of the brain take a
role in it (can also be the whole brain).
Epileptic seizures are due to abnormal electrical activity of a group of cells due to dysfunctional ion
channels. If you would perform an EEG, you would see clear abnormalities and you would be able to
locate where in the brain specifically this occurs + when it starts (the onset).
EEG
Within a neuron, the activity is determined by electrical processes, while between one neuron and
another, it is mainly determined by chemical synapses and neurotransmitters. A neuron has a
membrane potential. That means that the inside of the neuron is negatively charged compared to
the outside. This is about – 70 mV. There are different concentrations of ions on the inside versus the
outside cell. This is determined by active (Na +/K+ pump) and passive (ion-channels) processes.
Basic neuron physiology – Action potential
Membrane potential On the outside [Cl-]
and [Na+] are higher and on the inside [K+] and
protein concentrations are higher. The active
and passive processes make sure that in the
end you end up with -70 mV.
Neuron There are voltage gated Na+
channels. These only open when the
, membrane potential is increased, so when it becomes less negative. The threshold is about -
55 mV. There will be a huge influx of sodium into the cell. As sodium is positively charged, it
will increase the membrane potential, making it even positive. There will be an overshoot
and at that point the K+-channels will open, to make the membrane potential less negative
(hyperpolarization takes too long for potassium channels to close while the sodium
channel is already closed). It will eventually return to resting membrane potential. When
depolarization / action potential is taking place, the neighboring membrane will eventually
also go over the threshold and start to depolarize. This is propagation.
Basic neuron physiology – chemical synapse
Neurotransmitters release at synapse which initiates depolarization of membrane. Some action
potential arises from part of the cell which ends at the synapse. Calcium channels will open and a
large influx of calcium (Ca2+-ions) will arise. The channels will allow that the neurotransmitter within
synaptic vesicles are fused with the membrane and are released in the synaptic cleft. In post synaptic
cleft the neurotransmitter bind to receptors and result in either hyperpolarization or depolarization.
EPSP (Excitatory post-synaptic potential) causes depolarization and IPSP (Inhibitory post-synaptic
potential) causes hyperpolarization. Hyperpolarization makes the membrane potential less likely to
pass the threshold and fire an action potential. If a neurotransmitter causes EPSP or IPSP depends on
type of neurotransmitter. The sum of the PSP (post-synaptic potential) determines if neurons ‘fire’
which determines depolarization/action potential.
To sum up action potential to synapse influx calcium neurotransmitter vesicles fused with
membrane neurotransmitter released in synaptic cleft binds to receptors on post-synapse it
will either depolarize or hyperpolarize 2 options:
- Less negative EPSP depolarized.
- More negative IPSP hyperpolarized.
The sum of this will determine whether the neuron fires.
Electroencephalography 1 - EEG
20 billion of 80 billion neurons are in the cortex. EEG measures potential differences in the cortex.
There are some problems with EEG. One is that there are a lot of layers between the electrode and
neurons: brain layers, spine fluid and the skull (skull + scalp). Furthermore, it cannot obtain signals
from individual neurons. The signal from is a single neuron is too small. The neurons in the cortex are
pyramidal neurons they are in similar direction, large groups are activated quite synchronic called
concurrent activation which provides enough potential difference to be measured with an electrode
on the skull despite all layers in between.
History of the EEG
In the 19th century they removed skulls from animals and measured brain activity. In 1929 recordings
in humans with electrodes on scalp, so closed skull were performed. They could make a distinction
between slow (alpha) and fast (beta) waves which are detected on the EEG. They found out that the
alpha rhythm was less present when performing a difficult task.
Electroencephalography 2 - EEG
Electrodes are used which are small metal plates typically Ag or AgCl. Potential differences between
two electrode are measured over time. The potential is still very small so they have to be amplified
and be transformed in something which could be actually read (back in the day they used a pen).
They only used two electrodes in the early days. Nowadays analog-to-digital conversion is used and
also a lot of electrodes. The contact between the electrode and scalp is improved by a gel with ions
(salt paste) to improve conduction. Clinical EEG measurements are done in a standard way which is a
10-20 system and performed 20-30 minutes. EEG-activity is measured (when the patient is at rest)
and EEG-reactivity (when the patient performs tasks like opening and close the eyes).
,Typical activity always based on waves in certain frequencies:
Beta 14-30 Hz awake and mentally active
Alpha 8-13 Hz awake and resting
Theta 4-7 Hz Sleeping
Delta <3,5 Hz Deep sleep
So the smaller the frequency, the less active.
Alpha rhythm is the most famous brain rhythm. It is most clear when eyes are closed strongest in
occipital areas (where the visual area of the brain is). The potential is compared to the average of all
of them. There are very clear oscillations between 8 and 13 Hertz. The amplitude defines how strong
the incoming signal is, this can be used that one part of the brain is better perfused (blood flow). Low
amplitude can indicate less blood flow.
EEG artifacts
The EEG is susceptible for artifacts which are unwanted recorded differences due to biological or
technical reasons. This is because the EEG is non-specific it just measures any potential differences.
The heart for example is a big source of potential which can alter the EEG measurements. EEG in
itself only produces small potential differences. Also if people think of moving the same potentials
arise in the cortex as actually performing the movement. Things that cause artifacts:
Biological: blinks, yawning, eye movement, muscle activity (chewing, swallow, blinking)
Technical: movement, electrical equipment, conducting paste (too much or too few, when
too much the electrodes will touch each other).
Artifacts van be recognized by large amplitude, isolated electrodes and joint activity on multiple
nonadjacent electrodes (can for example touch a cable).
EEG – Epileptic seizure
During an epileptic seizure the EEG will be abnormal. Characterized by strong and synchronized
activity. Partial seizure when synchronized activity will only be in a few electrodes, however also
generalized seizure then all electrodes show synchronized activity. Patients do not always have
seizures and then the EEG is completely normal. Sometimes these patients do show inter-ictal
discharges (IID). To determine if a patient has epilepsy you want to provoke the brain into ‘abnormal
patterns’ or even a seizure. Things used are sleep deprivation before EEG, hyperventilation or light
flashing at high frequency.
Case conclusion: In absence epilepsy 3 Hz peak-wave complexes spontaneously occur. During
hyperventilation the patient goes into a seizure and stopped hyperventilation after a few second he
continued and did not notice he stopped. This patient can be treated with antiepileptic medication.
Absence epilepsy? Altered electrical brain activity/reactivity? Perform measurement of
electrical (re)activity (EEG) Altered means yes Confirm diagnosis (cycle)
Electroneurography (ENG) and electromyography (EMG)
Medical case 1: First case is a 33 year old woman with numbness and tingling in right arm and hand.
At night she wakes up because of numbness in her fingers. Complaints increase during daytime.
Neurological examination indicated no atrophy of the hand muscles (decrease of muscles) or
rheumatoid arthritis.
Medical case 2: is 61 year old male numbness, tingling and occasional pain in the thumb, index finger
and middle finger of both hands. Always present, but worsen at night. Possible atrophy of abductor
muscles in both hands but no decrease in strength.
, Carpal tunnel syndrome
Numbness and tingling in hands are symptoms of the carpal tunnel syndrome. It is caused by
compression of median nerve at the wrist. Posture-dependent compression, so in some posture the
symptoms will worsen. The median nerve is a mixed nerve which means sensory (numbness and
tingling) but also motor (weakness and atrophy). No clear cause could be congenital (from birth)
narrow carpal tunnel, hormonal (pregnancy), trauma or rheumatoid arthritis. There are two clinical
test Tinel’s sign should induce tingling at the affected area of the hand and Phalen’s test also induces
tingling and pain which indicates carpal tunnel syndrome. These are not good clinical test because
sometimes false negative. They are not very sensitive tests.
Carpal Tunnel Syndrome – Diagnosis – ENG
Electro neurography (ENG) can be performed. Most sensitive test for CTS diagnosis. It assesses the
conduction of the sensory nerves (sometimes also motor). Assessing peripheral nerve function of the
motor nerves:
1. Stimulate the nerve at some point along the nerve
a. How long did it take to arrive at the muscle?
2. Create an action potential
3. Measure arrival at other point along nerve (this indicates the functioning of the nerve)
In practice this cannot be performed on the nerve itself but it measures electrical activity of the
muscle with an EMG (nerve + neuromuscular junction + muscle). The axon will be stimulated on two
different positions compare responses for two distances. The contraction of muscle fibers is
measured with EMG. First stimulate axon electrically and wait a couple of milliseconds and then the
same on another points. The distance between the two points is measured as well as the time it took
before the muscles contracted. To calculate the conduction velocity a formula is used:
d
Velocity: v =
Δt
ENG and CMAP
In practice not one neuron is activated. The entire nerve is stimulated as result many muscle fibers
contract recorded with CMAP (compound muscle action potential) using ENG. Each stimulated axon
activates several muscle fibers and CMAP is the compound (all together) response of all muscle fiber
contractions.
Latency: time between stimulation and onset CMAP, says
something about the conduction velocity along the nerve,
neuromuscular junction, fibers. Determined by fastest fibers.
o Time delay between proximal (PML) and distal motor
latency (DML) can give actual conduction velocity of the
nerve.
o Higher latency? slower conduction nerve damaged?
Amplitude: amount of activated muscles.
The velocity of the latency can be calculated. This is the conduction velocity of one nerve.
Basics Peripheral nerve
A peripheral nerve exist of axons these are part of individual neurons can be up to a meter in length.
The axon is covered in a myelin sheet it functions as insulator. The axons transmit action potentials,
the myelin sheet makes jumping of action potential possible it increases the signaling speed. The
axons together are a fascicle and some fascicles together are a nerve which have a diameter of
several millimeters.
Motor nerves
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