Wk2 - Neuroscience Methods and Techniques Flashcards
Name 3 haemodynamic methods
MRI, fMRI, PET
Name 2 electrophysiological methods
Single-cell recording
EEG
What type of methods have superior spatial resolution?
Haemodynamic methods
What types of methods have superior temporal resolution?
Electrophysiological methods
Define spatial resolution
How much detail you can see? E.g., can you see brain differences at a neuron level or a synaptic level? Or can you only see what large portions of the brain are doing?
Define temporal resolution
How much time definition can you see? Can you see changes in the brain going on from millisecond to millisecond? Seconds? Minutes? Hours? Days?
How fast does the action potential occur?
1 millisecond
Why do haemodynamic methods have poor temporal resolution?
Because methods such as fMRI looks at blood flow. It takes a while for an area of the brain to use blood and have more blood going there. This doesn’t happen quickly.
What does fMRI measure?
Measures concentration of oxygen in the blood
What measurement is used to report the oxygen level in the blood that is picked up by fMRI?
BOLD contrast
What does BOLD stand for?
Blood oxygen level dependent
What property differences between oxygenated and deoxygenated blood?
Their magnetic properties
What does a strong BOLD signal indicate?
Areas of the brain that have more oxygenated blood going to them
What does a lower BOLD signal indicate?
Deoxygenated blood
What does blue on an fMRI image indicate? (3)
Deoxygenated blood
Lower BOLD signal
Less activity
What does red/yellow on an fMRI image indicate?
Oxygenated blood
Higher BOLD signal
More activity
Explain the 3 assumptions of fMRI
If a brain area is working harder, it will use up more blood and demand more blood.
This greater demand for oxygenated blood is indicated by a stronger BOLD signal.
Greater activity occurs in the more oxygen-rich region.
In a visual experiment, where would you expect to see a higher BOLD signal and why?
Visual cortex
Visual cortex will have used up the blood and will demand more oxygenated blood to go to it
Is fMRI a direct measure of brain activity?
No
fMRI looks at the indirect consequence of brain activity (the demand for oxygenated blood)
Does fMRI have high or low spatial resolution?
High
Does fMRI have high or low temporal resolution?
Low - changes in blood flow don’t occur rapidly
What does fMRI stand for?
Functional magnetic resonance imaging
Does fMRI measure changes in brain activity or changes in brain structure?
Changes in brain activity
How is oxygen carried in the blood?
By haemoglobin
What are the 2 types of haemoglobin?
Oxyhaemoglobin
Deoxyhaemoglobin
What type of haemoglobin has the stronger magnetic resonance signal?
Oxyhaemoglobin
Using fMRI how can we tell which parts of the brain are more active?
The more active brain regions would have used up more oxygen. These areas would therefore have more oxygenated blood going to them, thus giving a strong BOLD signal
What biological processes happen when a brain area is active?
Levels of oxyhaemoglobin will first decrease.
Deoxyhaemoglobin will increase because this brain area is using the oxygen.
The vascular system increases the flow of oxygenated blood to the area.
How does the BOLD signal work?
Shows us the amount of oxygenated blood compared to deoxygenated blood in areas of the brain to tell us which areas of the brain are more active
What type of image does an fMRI produce?
T2-weighted image
How can you recognise a T2-weighted image?
White matter = grey
Grey matter = white
Cerebrospinal fluid = bright white
What mechanism produces a T2 weighted image?
Relaxation of proton spin
What does MRI stand for?
Magnetic resonance imaging
Briefly, what does MRI do to hydrogen protons?
Artificially excites hydrogen protons and then measures their relaxation properties over time
Are electric and magnetic fields parallel or perpendicular?
Perpendicular
How is a magnetic field produced in MRI?
Current passes through electric coils which surrounding a patient in a clockwise rotation
Electric current produces a magnetic field longitudinal to the subject (from feet to head)
Where are hydrogen protons found?
Neural tissue
Fluids and organic compounds of the brain and body
How do protons spin?
Protons spin on an axis with a spinning positive charge (+1).
The positive charge moves from side to side.
What is the proton spin called?
Precess
How does the strength of the magnetic field affect the precession (spin) of the protons?
Strong magnetic field = faster spin
How do protons orientate normally?
The magnetic fields of individual protons normally orientate in random directions, with the positive and negative charges cancelling each other out
What happens if we put the protons into a larger magnetic field?
The protons will align with (become parallel to) the magnetic field created by the electric foils, orientating towards the subject’s head and feet
When protons are in this aligned state, what is applied?
A brief radiofrequency pulse
What does the radiofrequency pulse do?
Excites the protons
Knocks the orientation of the protons by 90 degrees so that they produce a change in the magnetic field
Creates a small magnetic field transverse to the subject
Synchronises proton spinning so that they precess in phase
What happens when the radiofrequency pulse stops?
The protons will relax back into their initial alignment along the longitudinal magnetic field
The protons return to precessing out of phase
What is the T1 relaxation time?
The time for the protons to relax and return to their original alignment
Can the T1 relaxation time vary?
Yes, the rate at which protons return back to their relaxed, aligned state depends on what type of tissue the protons are in
What are T1-weighted images used for?
Structural images of the brain
How can you recognise a T1-weighted image?
White matter = white
Grey matter = grey
Cerebrospinal fluid = black
What happens when protons precess in phase?
Increases the net magnetisation in that direction because the positive charges no longer cancel each other out
What is the T2 relaxation time?
The variation in the rate at which protons return back to their out-of-phase state following the radiofrequency pulse
Can the T2 relaxation time vary?
Yes, protons in different matter/types of tissue take different amount of times to go back out-of-phase
What are T2-weighted images used for?
Functional images of the brain
How are axial, sagittal, and coronal slices produced?
The MRI scanner sends radiofrequency pulses from different electric coils at different directions to excite protons at different slices
What are voxels?
3D cubic pixels that make up MRI images
What are the very small measures of brain that are used in MRI?
Voxels
What does the X coordinate of the voxel tell us?
How medial or lateral the voxel is
What does the Y coordinate of the voxel tell us?
How close to the front or back of the brain the voxel is
What does the Z coordinate tell us?
The depth/how dorsal or ventral the voxel is
What does PET stand for?
Positron emission tomography
What does PET involve?
Injection of a radioactive tracer into a biologically active molecule which travels around the blood
What sort of rays does the tracer produce?
Gamma rays
What does the gamma camera do?
Measures the gamma rays to show the concentration levels of the tracer in the blood
Is PET invasive?
Yes
Is PET safe?
Yes
Does PET have a high or low temporal resolution?
Low temporal resolution because we are talking about blood flow
What are 3 limitations of PET?
Invasive
Need shorter testing sessions so that the isotope doesn’t run out by the end of the testing session.
Participants can only be scanned once because it involves the injection of radioactive material.
What is an advantage of PET?
Can measure the metabolism of different kinds of substrates
What are the 2 most common tracers used in PET?
Oxygen-15
Fluorine-18
How is oxygen-15 administered?
In the form of water
How is fluorine-18 administered?
In the form of glucose
Using PET, how can we tell which areas of the brain are more active?
Active areas will have greater blood flow, thus will emit a greater signal by the tracer.
The area which more glucose is going to is more active because it needs more energy from the glucose
Is PET or fMRI used more and why?
fMRI is more commonly used because fMRI is more practical and gives more information
How does the tracer in the bloodstream produce gamma photons?
The tracer converts from the unstable radioactive form back to the normal stable form
This emits a positron particle that then collides with an electron to release 2 gamma photons
What detects gamma photons?
Detectors which are positioned around the head
Does PET or fMRI have better temporal resolution?
fMRI
Can you see causation or correlation with brain imaging techniques?
Correlation
We can measure brain activity which correlates with a particular task (neural correlate) but we cannot say that the task definitely causes the activity
Can you see causation or correlation with brain stimulation techniques?
Causation
What are 4 types of brain stimulation techniques?
Deep brain stimulation
TMS
tDCS
Optogenetics
How does DBS work?
An internal pulse generator (pacemaker) is implanted under the skin by the clavicle
Pacemaker sense electrical pulse to electrodes in the brain that are implanted in the exact-to-be-stimulated brain region
What are 4 advantages of DBS?
Fully reversible
Precise localisation
Few side-effects complications
Can be effective for Parkinson’s disease, chronic pain, depression, and OCD
What are 2 disadvantages of DBS?
Invasive
Can have severe side-effects/complications
What does TMS stand for?
Transcranial magnetic stimulation
How does TMS work?
Rapidly changing electromagnetic fields are applied to induce electrical currents inside the brain
What happens when TMS is applied repetitively?
Increases or decreases cortical excitability
What frequencies inhibit the cortex underneath it?
Low frequency stimulation
What frequencies activate or excite the cortex underneath it?
High frequency stimulation
Does TMS induce or increase the chance of action potentials?
TMS INDUCES action potentials
Is TMS or tDCS stronger?
TMS - can see very clear effects from using this stimulation
What does tDCS stand for?
Transcranial direct current stimulation
How does tDCS work?
A battery-powered device delivers direct current to a brain region through electrodes placed on the scalp in the region of interest
What electrodes are involved in tDCS?
Active electrode (red) Reference/passive/return electrode (blue)
What does the anodal (positive) electrode do in tDCS?
Anodal current stimulation can increase or decrease neuronal excitability of the cortex, and makes neurons more or less likely to fire, depending on the position of the electrodes
What does the cathodal (negative) electrode do in tDCS?
Nothing
Which part of the brain is the most stimulated during tDCS?
The area that is halfway between the anodal and cathodal electrodes
What is a disadvantage of tDCS?
The size of the electrodes are very big - difficult to accurately localise stimulation. Stimulate all the area between the two electrodes.
Does tDCS induce or increase the likelihood of an action potential occurring?
tDCS increases or decreases the likelihood of neurons potential to fire by changing their membrane potential
What does tDCS do to neurons?
Changes their membrane potential
How does optogenetics work?
Alters the genes to allow expression of light-sensitive proteins in particular types of neural cells.
Then shine a coloured light inside the brain to switch on or switch off cells in a particular area
What is an advantage of optogenetics?
Can target very specific cells in an area, rather than just an entire region
What is a disadvantage of optogenetics?
Invasive - light is shone inside the skull to stimulate cells
Who invented EEG?
Hans Berger
What activity does EEG record?
EEG records the electrical activity of neurons that can be picked up from the scalp
How many neurons are needed for activity to be recorded?
A large number that are active synchronously
What is a disadvantage of EEG?
Poor spatial resolution - current travels differently through brain matter and skull of different texture and density.
Can pick up an electrical signal from one part of the scalp but this doesn’t mean that the signal is made by the neurons directly underneath that part of the scalp.
Electric current loses potency and encounters resistance as it moves through brain matter
How is electrical activity recorded in EEG?
Electrodes clipped onto a scalp cap with either 32, 64, or 128 electrodes
How are the electrodes labelled on the scalp?
The electrodes are labelled with letters and numbers according to their position on the head
Is it better to have more or less electrodes on the scalp in an EEG?
More - the more electrodes that we have on the scalp, the better chance we have of localising the source
What is the purpose of reference electrodes in an EEG?
The reference electrode picks up the rest of the ‘background’ voltage so that it can be used as a comparison.
Can calculate the EEG output as the difference between the voltage recorded at one electrode and the voltage recorded at the reference electrode.
Where abouts can the reference electrode be placed?
Mastoid (the bone behind the ears)
Earlobes
Nose
Where abouts is the reference electrode commonly placed?
One on each ear lobe. Mean is calculated.
What activity is recorded on an EEG?
Post-synaptic potentials
How do post-synaptic potentials differ from action potentials?
Post-synaptic potentials propagate much further in extra-cellular space and have a longer duration
Why is it good that post-synaptic potentials have a longer duration than action potentials?
A longer duration means that there is a greater probability of multiple PSPs overlapping. Thus, there is more synchronised activity. We have a larger amount of active cortex that we can pick up activation from.
What type of brainwave is seen on an EEG?
Alpha
What is the Hz range of alpha waves?
8-12 Hz
What does it mean if an alpha wave oscillates at 8-12 Hz?
There are 8-12 wave cycles per second
What is the frequency range of brain oscillations?
0.5 - 1000 Hz
What are the names of the 5 frequency bands?
Gamma
Beta
Alpha
Theta
Delta
Which wave has the lowest frequency?
Delta (0.5 - 4 Hz)
Which wave has the highest frequency?
Gamma (32 - 40 Hz)
Are different wave frequencies related to different functions?
Yes, but we are not sure exactly how they work yet
What functions are delta waves associated with?
Biologically motivated functions
What functions are theta waves associated with?
Memory, language
What functions are alpha waves associated with?
Inhibition, lower cortical excitability
What functions are beta waves associated with?
Movement, anxiety
What functions are gamma waves associated with?
Higher cognitive functions, consciousness
If someone is taking part in a memory experiment, what wave activity are we likely to have a large amount of?
Theta
Where is one of the primary sources of theta activity?
Hippocampus
What is the hippocampus related to?
Memory
What 3 types of analyses can be done when looking at the 5 wave frequencies?
Power analysis
Time-frequency analysis
Synchronisation analysis
What does a power analysis look at?
Looks at the mean amount of power of particular frequencies in different regions over a particular period of time (during resting state, or after a stimulus, for example)
What does a time-frequency analysis look at?
Looks at the changes in frequency over a short time (e.g., see how theta activity increases or decreases over 500 ms)
What does a synchronisation analysis look at?
Looks at the way that frequency in one area of the brain might covary or synchronise with another
What is synchronised activity essential for?
Coherent thought and action
What do transient periods of synchronised activity do?
Bind brain regions and processes. Enables us to put processes together coherently to carry out complex sequences (e.g., catching a ball)
What does synchronisation of phase mean?
Waves going up and down at the same time
Are phase and amplitude related?
No. It doesn’t matter if waves have different amplitudes, they can still synchronise
What 2 ways can EEGs be analysed?
Wave (oscillation) frequencies
ERPs
What does ERP stand for?
Event-related potential
What do ERPs show us?
The brain activity related to an event or stimulus
What are ERPs?
Small voltages generated in the brain structures in response to specific events or stimuli
How are ERPs formed?
EEG segments of activity immediately after a stimulus is presented are averaged to get an ERP waveform
Where will positive values and negative values be on an ERP voltage by time plot?
Positive values are at the bottom and negative values are at the top of the Y-axis (voltage)
How are peaks named?
According to the time they occur and their polarity
What is the first positive peak called?
P1 (will appear lower on the graph)
What is the first negative peak called?
N1 (will appear higher on the graph)
Which components in an ERP are more predictable?
Early components
What are early components on an ERP associated with?
Perceptual and attentional processes
Which components of an ERP are less predictable?
Later components
What are later components on an ERP associated with?
Higher level cognitive and evaluative processes (e.g., may reflect evaluation of stimulus meaning and relevance)
How do different components on an ERP come about?
Different type of stimulus used
Different task used
What stimuli would cause a bigger, more positive P1?
Stimuli which captures somebody’s attention more quickly (e.g., a bigger word compared to a smaller word)
What might happen to P1 to indicate that processing is occurring quicker than usual?
P100 may come in at P80 milliseconds
What might a larger later component indicate?
More meaningful stimulus processing
Is the polarity of the ERP meaningful?
No, it doesn’t matter whether peaks are positive or negative
What does the polarity of the ERP depend on?
The baseline electrical activity and the position of the reference electrode
What aspects of the ERP are we interested in?
Timing (latency)
Size (amplitude)
What aspect of the ERP are we not interested in?
Polarity
What do single-cell recordings measure?
Directly measures the action potentials of a single cell (neuron)
How does single-cell recording work?
A microelectrode is implanted in the head and either placed inside of the axon or outside of the axon.
The microelectrode detects the electrical signal and passes it on to the amplifier.
Amplifier compares the recording to a ground electrode.
Signal is passed on to an oscilloscope and/or computer
What is a disadvantage of single-cell recordings?
Extremely invasive - brain surgery is required to implant the electrode. There is no way to record action potentials themselves outside of the skull.
What does an oscilloscope or computer present?
A visual display of the membrane potential over time
What can we record using single-cell recordings?
The frequency of action potentials in a particular neuron
What is the purpose of a ground electrode in single-cell recordings?
Reference electrode. Allows a comparison of the voltage.
What does the amplifier in single-cell recordings do?
Amplifies the signal by 100-1000 times because we are looking at tiny differences in voltage.
Amplifies and compares the signals and sends this information to the oscilloscope.
When might single-cell recordings be used?
To find out if the frequency of action potentials in a particular neuron is affected by a particular stimulus
To find out the role of a particular neuron in a given sensory, motor, or cognitive behaviour
To find out how the activity or inactivity of one neuron affects the activity of another neuron
What information can we gather about a stimulus from a single-cell recording?
Whether or not the stimulus leads to specific changes in voltage (microvolts)
Where does protein synthesis of neurotransmitters occur in a neuron?
Nucleus
What is another word for the cell body of a nucleus?
Soma
Where is the axon hillock?
Top of the axon
What happens at the axon hillock?
Action potentials are triggered
What are found at the axon terminals?
Terminal buttons
What happens at the terminal buttons?
Neurotransmitters are released into the synapse
Define synapse
The small gap in between the terminal buttons and the dendrite (or soma) of the next neuron
Do all neurons have a myelin sheath?
No
What is the myelin sheath made up of?
Glial cells
What is the purpose of the myelin sheath?
Insulates the axon and increases the speed of action potential propagation
Where are the Nodes of Ranvier?
Gaps in the myelin sheath
What happens at the nodes of ranvier?
Action potentials are regenerated at each of the nodes, causing the action potential to travel faster
Define resting potential
The difference in charge between the inside and the outside of the cell
What maintains the resting potential?
Concentration gradients, electrostatic gradients, ion channels
K+ channels open allowing an equal amount of K+ in and out (both concentration & electrostatic gradients)
What is an ion?
A charged particle with an uneven number of protons and electrons
What is current?
The movement of ions across the membrane
Which 3 ions are important to neural communication?
Na+
K+
Cl-
What are 2 ways of transport in which ions can move across the membrane?
Passive movement along a concentration or electrostatic gradient
Active transport through pumps
What is the difference between concentration and electrostatic gradients?
Concentration gradients work so that there is an even concentration of ions on either side of the membrane.
Electrostatic gradients work so that there is an even charge on either side of the membrane. Not necessarily an equal concentration gradient.
How does the active pump work?
Moves 2 K+ into the cell
Moves 3 Na+ out of the cell
Inside of the cell becomes more negative
What voltage is the resting potential?
-70mV
What does -70mV mean?
The voltage on the inside of the cell is -70 less (more negative) than the voltage on the outside of the cell
What does it mean if a neuron depolarises the neighbouring cell?
Makes the membrane potential more posiive
What does it mean if a neuron hyperpolarises the neighbouring cell?
Makes the membrane potential more negative
How does depolarisation of the next cell occur?
Excitatory neurotransmitters bind to ligand-gated ion channels.
Na+ channels open and Na+ enters.
The cell is made more positive.
The cell is more likely to fire.
What are 2 excitatory neurotransmitters?
Acetylcholine
Glutamate
What do excitatory neurotransmitters do?
Make the membrane potential more positive (allows entry of Na+ or K+) and makes the cell more likely to fire.
What are the 2 types of post-synaptic potentials?
Excitatory (EPSP)
Inhibitory (IPSP)
What is an example of an inhibitory neurotransmitter?
GABA
How can GABA induce an inhibitory post-synaptic potential?
GABA binds to receptors on the post-synaptic dendrite.
This opens Cl- channels. Cl- ions enter and make the cell more negative (hyperpolarises the cell).
The cell becomes less likely to fire and make an action potential.
Cl- then conduct passively along the dendrite where they encounter resistance and often don’t make it to the axon hillock.
How does an action potential occur from a post-synaptic potential?
The positive charges from from multiple EPSPs and IPSPs will be summed at the axon hillock.
A net positive charge will depolarise the cell.
If the net charge is positive enough, it will depolarise the membrane to a threshold point and an action potential will occur at the axon hillock.
How many volts is the threshold point?
-55 mV
What happens during an action potential?
-55 mV threshold reached. Na+ ions enter the cell. Cell becomes more positive. Na+ channels close and K+ open so that K+ leaves the cell. Cell is repolarised. Cell hyperpolarises before the K+ channels shut. K+ channels close and the cell goes back to its resting state of -70 mV.
What does hyperpolarisation mean for action potentials?
When a cell is hyperpolarised, it is more negative and it is therefore a lot harder for the cell to have an additional action potential occur.
It is unlikely that an action potential will occur whilst the cell is hyperpolarised. Far more positive charges will be needed to add up to reach the -50 / -55 mV threshold.
How does the action potential travel down an unmyelinated axon?
Opens adjacent Na+ channels and the cycle continues down the axon to the axon terminal.
Smooth movement of action potential.
How does the action potential travel down a myelinated axon?
The action potential goes through passive conductance through the myelin.
The myelin covers up the axon, meaning that it cannot open any channels.
Action potential is regenerated at the Nodes of Ranvier (there is a gap and channels can open so the action potential is regenerated at that point)
Action potential continues to passively conduct and regenerate, jumping down the length of the axon
Does the action potential travel faster in myelinated or unmyelinated axons?
Myelinated axons
When might the action potential increase in frequency?
If a more salient stimulus is used then there is a greater frequency of neurotransmitter release.
Can the action potential increase in both frequency and amplitude?
No, the action potential cannot increase in amplitude.
What aspects of the action potential might differ when a different stimulus is used?
Frequency of action potentials
Frequency of neurotransmitter release
Type of neurotransmitter or receptor involved
Whether post-synaptic potentials are excitatory or inhibitory
