BME 301 Final

central nervous system

brain + spinal cord → processing center

sensory → body → brain

peripheral nervous system

all nerves outside → carries info

motor → brain → body

how a patch clamp works

-tiny glass pipette touches cell membrane

-forms a tight seal → measures ion flow through 1 channel

-converts tiny currents (picoamps) into measurable signals

the gigaseal

-extremely tight seal (10-100 gigaohms)

-ensures all current measures = from the channel only

configurations of the patch clamp

-cell-attached → measure channel, cell intact

-whole-cell → inside of cell connected to pipette (most common)

-inside-out → inside of membrane exposed

-outside-out → outside exposed (lets you test different environments)

use of patch clamp/patch clamp equipment

-study ion channels

-measure: current, voltage, firing patterns

-understand how neurons signal

patch clamp recordings

-show channel opening/closing over time

-you see “blips” = channel briefly opening/closing (reveals kinetics of channels)

types of channels

-voltage-gated

-ligand-gated

-chemically-gated

-mechanically-gated

voltage-gated channels

-open when membrane voltage changes

-Ex: Na+ channels in action potentials (depolarization opens them)

ligand-gated channels

-open when neurotransmitter binds

-Ex: acetylcholine receptor (like a lock and key)

sensory neurons

-convert stimuli → electrical signals (voltage)

-output: graded potential or action potential

sensory signals

stimulus → receptor → electrical signal → brain

sensory transduction

-conversion: physical stimulus → electrical signal

-Ex: light → voltage in eye

classes of sensory receptors

-mechanoreceptors → touch/pressure

-photoreceptors → light

-chemoreceptors → taste/smell

-thermoreceptors → temperature

-nociceptors → pain

difference between receptors and channels

-receptor = detects signal

-channel = lets ions flow

-sometimes combined (ligand-gated channels do both)

how receptors let us hear sounds

-sound → vibrations → fluid movement in cochlea

-moves hair cells → opens channels → electrical signal

frequency modulation

different sound frequencies → activate different regions of cochlea → brain interprets pitch

cochlear implants

-bypass damaged hair cells

-directly stimulate auditory nerve with electrodes

receptors in the skin

detect pressure, vibration, temperature, pain

receptive fields

-area of skin a neuron responds to

-small field → high precision

-large field → less precision

meissner corpuscles

-light touch

-fast adapting

-high sensitivity (fingertips)

pacinian corpuscles

-deep pressure and vibration

-very fast adapting

adaptation

-receptors stop responding to constant stimulus

-Ex: stop noticing clothes

transmitting sensory information to the brain

1. receptor activated

2. signal travels via neuron

3. reaches CNS

dorsal ganglion

-contains sensory neuron cell bodies

-entry point into spinal cord

sensory cortex/homunculus

-brain map of body

-some areas (hands, face) = larger representation

receptive fields and brain space

more receptors → more brain space → better sensitivity

reorganization of brain sensory processing

-brain can reorganize after injury or experience

-Ex: losing limb → remapping

pain receptors/perception

detect damage (heat, chemicals, pressure)

TRP channels (TRPV1)

-respond to: heat, capsaicin (spicy food)

-key in pain sensation

central nervous system

brain and spinal cord

peripheral nervous system

takes signals from the brain and brings them to the rest of the body. The PNS includes sensory neurons for perceiving the environment and motor neurons for stimulating muscles

what is a synapse and what happens there

in the brain, the electrical signal propagated down a neuron (the action potential) is converted into a chemical signal at a synapse. the chemical signal then triggers a new electrical signal in the neighboring neuron. this differs from heart muscle cells, which communicate directly through electrical gap junctions

ligand-gated ion channels

generate EEG signals by controlling fast synaptic neurotransmission, directly impacting synaptic currents and neuronal excitability

inhibitory and excitatory glutamate receptors (AMPA, NMDA) are primary drivers of EEG oscillations acting as therapeutic targets in diseases like epilepsy and encephalopathy

they are synaptic receptors that convert chemical neurotransmitters into graded electrical PSPs by opening only when a specific ligand (GABA) binds to them

how does an action potential propagate down a neuron and result in neurotransmitter release

these signals are propagated through the opening and closing of voltage-gated sodium and potassium channels, governed by the hodgkin-huxley equations

why use electrical and chemical signals (advantages/disadvantages)

electrical signals (action potentials) are fast and efficient for long-distance travel down axons

chemical signals at synapses allow for complex interactions, such as inhibition or excitation of the next cell

post-synaptic potentials

local electrical changes in a neurons dendrites triggered by chemical neurotransmitters at a synapse

unlike action potentials, PSPs are passive and graded; they do not maintain a constant magnitude and instead decay exponentially over time and distance

EEG signal measured at the scalp represents the summation and synchronization of thousands of these potentials firing in unison within cortical columns

10-20 system

clinicians use a standard placement system, often referring to the 10-20 system, which defines electrode locations based on specific percentages of the head’s dimensions

how do cortical columns enable the EEG signal

brains gray matter contains densely packed cell bodies, while the white matter consists of axons that connect different regions

the EEG signal largely results from the summation and synchronization of post-synaptic potentials in large groups of neurons firing in unison

EEG set up

standard EEG setup follows the 10-20 system

uses anatomical landmarks (the nasion (nose) and the inion (back of the head)

to calculate electrode positions based on 10% and 20% increments of the total distance around the skull

summation of post-synaptic potentials

EEG measured at the scalp is an aggregate signal

individual action potentials are too fast and involve too little voltage to be detected through the skull; instead, the EEG primarily reflects the summation of thousands of passive, sub-threshold post-synaptic potentials

these potentials occur in the dendrites and are integrated spatially and temporally by the neurons soma

synchronization of postsynaptic potentials

for the summed potentials to reach the scalp with enough magnitude to be recorded, the neurons must fire in synchrony

this is enabled by the organization of neurons into cortical columns, where large populations of cells are oriented in the same direction and fire in unison

without the synchronization, the individual electrical fields would cancel each other out before reaching the electrodes

EEG signals resulting from glutamate or GABA at two positions on the neuron

the shape or polarity of an EEG wave is determined by both the neurotransmitter type and the physical location of the synapse on the neuron

• neurotransmitters: excitatory transmitters (glutamate) cause an influx of positive ions (depolarization), while inhibitory transmitters like GABA typically cause an influx of negative ions or efflux of positive ions (hyperpolarization)

• position: whether these events occur at the apical dendrites (near the surface) or basal dendrites (deeper) creates different electrical dipoles. The orientation of these dipoles determines whether the electrode at the scalp records a positive or negative deflection

depolarization vs hyperpolarization EEG signals

depolarization: excitatory postsynaptic potentials moves the membrane potential closer to the firing threshold

hyperpolarization: inhibitory post-synaptics potentials moves it further away

the EEG captures the net electrical shifts resulting from these combined excitatory and inhibitory interactions, which are often disrupted in conditions like epilepsy or parkinson’s disease

EEG frequency bands

brain activity is categorized (alpha, beta, theta, delta), which can be analyzed using the fourier transform

ex. alpha blocking refers to the reduction of alpha wave activity when a person opens their eyes or concentrates on a task

mathematical modeling of the EEG signal

aggregate signal resulting from the summation of thousands of individual post synaptic potentials

unlike action potentials, which are too fast to summate, the PSPs last longs which allows them to overlap and create a detectable signal at the scalp

model assumes these signals originate from neurons organized in cortical columns where the parallel orientation of the cells allow their electrical dipoles to add together instead of cancel out

meaning of the Green’s function in EEG

mathematical tool to describe the relationship between the electrical source inside the brain and the potential measured at a specific electrode on the scalp

acts as a “weighting function” that accounts for the geometry and conductive properties of the head (brain, skull, scalp)

by knowing green’s function, researchers can perform forward modeling (calculating EEG from known brain source) or attempt inverse modeling (estimating brain source from measured EEG

advantages of increasing number of electrode

increasing number of electrodes (moving from basic 64 channel or 128) provides higher spatial resolution which allows for:

• more accurate topographical mapping: better visualization of where specific activity (like alpha waves or seizures) is localized on the scalp

• source localization: improved ability to mathematically “triangulate” the internal brain source of an electrical signal

• better denoising: higher electrode density makes it easier to identify and subtract artifacts like muscle movements or eye blinks

eye blink

shows the magnitude of bioelectric signals

individual post-synaptic potentials are very small, an eye blink creates a massive electrical artifact that can swamp the actual brain signal

clinicians use this to teach students about signal to noise ratio in EEG

signals of interest (brain activity) are often much smaller than the biological noise created by muscles or eyes

alpha blocking

sudden reduction or suppression of alpha waves (8-13 Hz) in the EEG signal

occurs when a person is in a relaxed state with their eyes closed (where alpha is prominent) and then opens their eyes or behins a demanding mental task

reflects shift from synchronized, rhythmic activity to the “de-synchronized” activity associated with active processing

Epilepsy

Excitatory and inhibitory interactions and how they’re affected in Parkinson’s disease

epilepsy characterized by synchronized, excessive neural firing

parkinson’s disease, involving disruptions in excitatory and inhibitory interactions

MEG

a companion to EEG that measures the magnetic fields produced by brain activity

TMS (transcranial magnetic stimulation)

sits on the head and uses magnetic fields to create electrical pulses that trigger action potentials in specific brain regions, such as the prefrontal cortex to treat conditions like PTSD

using EEG to brain computer interfaces

bioelectricity principles allow for the creation of interfaces that record brain signals to control external devices, such as prosthetic limbs, however, these signals are often complex with a low signal-to-noise ratio, requiring advanced engineering solutions to decode

Central nervous system (CNS)

brain and spinal cord

peripheral nervous system (PNS)

carries signals between the CNS and the rest of the body

contains sensory neurons (sensing the environment) and motor neurons (connecting to muscles to trigger movement)

what EMG measures

electromyography records electrical activity of skeletal muscles

measures the complex interplay between motor neurons and the muscle fibers they innervate

at rest, healthy muscles do not produce an electrical signal; signals only appear during contraction

motor unit

fundamental unit of EMG

single motor neuron and all the muscle fibers it innervates

firing is “all-or-none” when an action potential reaches the muscle, all connected fibers contract fully

intermingled motor units

muscle fibers from different motor units are not clumped together but are intermingled throughout the muscle

allows for smooth muscle contraction across the entire tissue rather than jerky movements in one spot

innervation ratios

the number of fibers per motor unit varies by function

areas requiring fine control (eyes or hands) have low ratios (about 10 fibers/neuron) while power heavy areas (legs) can have up to 2,000 fibers per neuron

order of motor unit recruitment (size principle)

motor units are recruited in a fixed order based on size

smaller motor units are easier to depolarize and are recruited first for light tasks; larger, more powerful units come online as more force is required

slow-twitch muscle (type I)

use aerobic respiration (oxygen), produce low power over long periods, and are fatigue-resistant

fast-twitch (type IIb)

use anaerobic glycolysis, produce high power quickly, but fatigue rapidly

rate coding and sychronization

force can also be increased by rate coding - increasing the frequency of action potentials until they fuse into a steady force called tetanus

motor units usually fire asynchronously, training or extreme stress can lead to synchronization, allowing for greater force without increasing muscle mass

motor unit fiber recruitment

the relationship between force and the number of recruited motor units is non-linear because larger units (with more fibers) are added later

EMG signal definition

a mathematical sum of all motor unit action potentials (MUAPs) within reach of the electrode, combined with thier specific firing patterns over time

EMG noise

signal is often “messy” due to various noise sources: line interference (60 Hz from power outlets), biological noise (like hearts ECG signal), line contact gaps, and subcutaneous fat, which acts as a resistor that attenuates the signal

muscle fatigue

a decrease in power or force despite the same contractile effort

muscle fatigue: central vs peripheral

peripheral fatigue occurs after the neuromuscular junction (muscle side), while central fatigue happens in the CNS when firing rates cannot be maintained

muscle fatigue EMG changes

fatigue causes a shift toward lower frequencies in the fourier spectrum and an increase in signal width often leading to visible trembling as the body tries to synchronize the few remaining functional motor units

motor neurons

a stimulator provides an electrical pulse to the nerve, and a recording electrode over the muscle measures the compound muscle action potential (CMAP)

sensory neurons

similar to motor studies, but the electrode is placed over a sensory nerve (finger) to measure the sensory nerve action potential (SNAP)

EMG for motor neurons variables

key measurements include amplitude (how high the peak is), latency (time from stimulus to onset/peak), and conduction velocity. the F-wave can also be measured, representing a signal that travels to the spinal cord and “backfires” to the muscle

nerve diameter and velocity

a general “rule of thumb” relates conduction velocity (v in m/s) to diameter (d in um) v=6 x d

effect of diabetes on nerves and EMG

high blood sugar damages vessels, depriving nerves of nutrients and leading to neuropathy, characterized by decreased EMG amplitudes

wallerian degeneration

if an axon is damaged, the injury propagates distally (down the axon). this makes it difficult to pinpoint the exact start of damage in axonal diseases

guillain-barre syndrome

an inflammatory disorder where the immune system attacks myelin

this causes immediate conduction blocks (slowed/diminished signals), but because the axon remains intact, patients can often recover as myelin is rebuilt

EMG clinical use

EMG is used to diagnose carpal tunnel, back pain, and ALS

also powers targeted muscle reinnervation, a technique where nerves from a missing limb are moved to existing muscles to act as “biological amplifiers” for controlling high-tech prosthetics

nerve conduction variables

in both motor and sensory studies, clinicians evaluate several key variables to diagnose conditions like carpal tunnel syndrome, diabetes, or guillain-barre syndrome

-amplitude: measures height of the signal peak (CMAP) mV (SNAP) microvolts: a decrease in amplitude typically indicates axonal degernation or loss of nerve fibers

-latency: time it takes for the signal to travel from the stimulus to the recording electrode. distal latency: time required to travel the final segment to the muscle or sensory site

-conduction velocity: speed at which the impulse travels down the never, calculated by dividing the distance between two stimulation by the difference in their latencies

-F-wave: represents a signal that travels proximally to the spinal cord and “backfires: down the nerve to the muscle

relationship between nerve diameter and conduction velocity

speed of electrical conduction is physically limited by the axial resistance of the neuron

according to the core conductor model. As the diameter of an axon increases, the internal resistance decreases, allowing the signal to travel more quickly

explains why larger motor neurons conduct signals much faster than smaller sensory fibers. understanding these variables allows engineers and clinicians to model how signals propagate passively or via action potentials across various pathologies

Biology of the heart

• Consists of four chambers

• Two atria on top that pump blood into two ventricles on the bottom

• The left ventricle is the “workhorse” of the heart, requiring thicker muscle to pump oxygenated blood throughout the entire body

• Valves (tricuspid, pulmonary, and aortic) ensure that blood flows in only one direction and does not backflow into previous chambers

Excitation-Contraction Coupling and how it protects the heart

• Electrical activation (an action potential) leads to a mechanical contraction of the muscle

• The heart is designed so the peak contraction occurs during the refractory period, which prevents a dangerous state called tetanus where the muscle would be stuck in a tightened position 

How the heart creates action potentials.

• The heart's rhythm is set by self-excitatory pacemaker cells in the Sinoatrial (SA) node, which fire about 70 times per minute 

• A secondary pacemaker, the Atrioventricular (AV) node, can take over at about 50 beats per minute if the SA node fails

Signal propagation in the heart

• The electrical signal starts at the SA node, spreads through the Atria, pauses briefly at the AV node to allow the ventricles to fill with blood, and then travels through the bundle of his and bundle branches to the ventricles

Role of Purkinje fibers.

• Specialized fibers that conduct the electrical signal to the heart muscle cells, triggering the final contraction of the ventricles

Voltage/current in heart cells

• Using the core conductor model, the heart can be modeled as a circuit where current moves axially inside and outside the cell and across the membrane. The net total of inside and outside current must equal zero.

Depolarization wave in the heart (and how it’s read on ECG)

• Involves positive ions rushing into cells, creating a negative charge immediately outside that is read as a positive deflection on an ECG when moving toward an electrode

Repolarization wave in the heart (and how it’s read on ECG). 

• Returns cells to their resting potential and is read as a negative deflection when moving toward an electrode

ECG signal

• Aggregate signal that records the total sum of electrical activity from many heart cells as it reaches electrodes in the surface of the body. It cannot distinguish individual action potentials but reflects major biological events

Role of sodium, potassium and calcium in heart action potential.

• Like neurons, sodium causes rapid depolarization. However, calcium plays a role in the heart by flowing into the cell later, which significantly prolongs the duration of the action potential. Potassium then flows out to cause repolarization

Components of ECG. 

• The P wave represents atrial depolarization, the QRS complex represents ventricular depolarization (dominated by the left ventricle), and the T wave represents ventricular depolarization

Einthoven’s triangle. 

• Uses three electrodes on the limbs to create Leads I, II, and III, which provide different “views” or projections of the heart’s electrical vector

Goldberger Augmented Leads.

• (aVR, aVL, aVF) bisect the original leads to improve resolution 

“View” of the heart from ECG Leads. 

• Different perspectives from which we can observe the heart's total electrical activity represented by a vector of depolarization

• Because the heart is oriented on a tilt and its electrical signal propagates in specific directions, different electrode placements allow us to see how that activity is projected along various axes

• Frontal plane view (limb leads), Einthoven's triangle (right arm, left arm, left leg), Goldberger augmented leads (aVR, aVL, aVF), horizontal plane view (chest leads) 

12-Lead ECG. 

• Includes the Goldberger 6 plus 6 unipolar chest leads (V1-V6) for a comprehensive picture of heart function 

Using ECG clinically. 

• ECGs diagnose conditions like arrhythmia (irregularity), ischemia (low oxygen), and infarction (tissue death/heart attack)

• ST elevation on the readout is a classic hallmark of a myocardial infarction

Ectopic heartbeat. 

• Occurs when cells outside the SA node spontaneously depolarize too early, creating a “flutter” or skipped beat feeling

How does your Apple Watch take an ECG?

• Takes ECG using two physical electrodes to recreate Lead I of a standard 12-lead ECG.

• One electrode is located on the back of the watch and the second electrode is on the digital crown, which the user must touch with their opposite hand to complete the circuit

• By measuring the potential difference between the right and left arms, the watch can generate a rhythm strip primarily used to detect atrial fibrillation 

How do pacemakers work. 

• Implantable devices designed to regulate the heart’s rhythm when its natural pacemaking cells (sinoatrial SA node) fail to function correctly 

• Work by delivering small, evenly timed electrical shocks to one or more chambers of the heart to maintain a steady heartbeat

• Typical system consists of a generator implanted under the skin near the collarbone and leads (wires) that are threaded through a vein and into the heart's chambers

• Sme advanced versions (implantable cardioverter defibrillators) can also sense if the heart has stopped and deliver a powerful shock to restart the heart