Imaging Flashcards
Aspiration
WHAT IS IT? HOW DOES IT WORK?
. The earliest methods of lesioning involved aspirating brain regions using a suction device and applying a strong current at the end of an electrode tip to seal the wound. These methods could potentially damage both gray matter and the underlying white matter that carries information to distant regions.
(LESION METHOD IN NON HUMAN ANIMALS)
- CON - DAMAGES WHITE MATTER TRACTS
How do fMRI/PET compare with ERP?
- Spatial Resolution: higher
- Temporal Resolution: lower
- Direct/Indirect measure of neural activity
▫fMRI/PET: Indirect
▫ERP: Direct
What does TMS do?
•Non-invasive focal stimulation of the brain
- TMS coil creates a magnetic field
- Induces a current in nearby neurons
- Disrupts ongoing activity
- Effects are generally subtle
Everyone pat your head
Now rub your tummy
Are you as good at patting your head when I get you to rub your tummy?
What happens:
Imagine neurons are involved in some task: they have a job to do
So they’re firing action potentials that are important for that task
Now you give them another job to do
Fire action potentials because of the magnetic field
Are they going to be able to do their real job as well?
Important point: stimulating visual cortex doesn’t make people see pictures in their mind’s eye; disrupts ongoing activity
Effects are subtle: changes in reaction times, not blindness
What type of imaging?
Axial CT Scan
CT Scans (Computerized Tomography)
•X-ray absorption is correlated with tissue density (bone > tissue > CSF)
▫High-density regions light colored; low-density dark colored
- Spatial resolution is ~ .5 to 1 cm; difficult to distinguish gray/white matter
- Mostly used in medical contexts
•
pixel and voxel
pixel- smallest distinguishable box-
voxel- volume pixel. 3 dimensional version of a pixel
•Infer the function of a region (or cognitive mechanism) by removing it and measuring the effect on the rest of the system
•
•For example, if damage to a region disrupts reading, but not speaking or seeing, then one might conclude that the region is specialized for some aspect of processing text
•
•Disruption of brain function comes about through natural damage (strokes, etc.), elicited damage (e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
•
?
what is a Voxel?
•volume elements (think of 3D pixels)
▫Voxels contain hundreds of thousands of neurons
Cognitive subtraction - What is it?
- Brain is always “active”; can’t just look at a single task
- Cognitive subtraction: compare activation during task of interest to control task
▫Control task should have all the same cognitive requirements as the experimental task, minus the one property of interest
What is a Positron Emission Tomography (PET)?
- Measures local blood flow, or regional cerebral blood flow (rCBF), associated with a give cognitive task
- Radioactive tracer injected into blood stream (invasive)
•
- Tracer takes up to 30 seconds to peak
- Temporal resolution ~30 seconds
- Spatial resolution ~5-10 mm
•
What do we use Functional Imaging for?
•Studying Cognition with
What Does it Mean to Say a Brain Region is “Active”?
•What to do?
▫Compare RELATIVE differences in brain activity between two or more conditions
•A region is “active” if it shows a greater response in one condition relative to another: cognitive subtraction.
•
Control conditions for TMS - What are the options? How do they work as a control?
•“Sham” TMS: hold coil over head
▫Not so good: does not control for noise, twitching
•TMS stimulation in a non-critical region
•TMS stimulation in a non-critical time period
Non-critical region:
If function is lateralized, same side on opposite side of brain
Non-critical time period
Remember: TMS has excellent temporal resolution: only lasts a few milliseconds
Imagine we want to disrupt visual processing
Primary visual cortex needs 100ms to process a stimulus
So we could give the pulse after 100ms
What is TMS?
•Transcranial magnetic stimulation
▫“reversible lesions”
Structural imaging studies what? With which methods?
Structural: studies brain anatomy. (CT, MRI)
MRI PHYSICS IN A NUTSHELL
Why look at hydrogen?
•Looking at magnetic properties of hydrogen protons
▫Our bodies have lots of water, so lots of hydrogen, so lots of protons
•Under the influence of an external magnetic field and radio waves:
▫Protons behave differently depending on what kind of tissue they’re in (white/grey/CSF)
•MRI = a map of different behavior — Map of different behavior gives you a map of different tissue
Neurochemical lesions
WHAT IS IT? HOW DOES IT WORK?
. Certain toxins are taken up by selective neurotransmitter systems (e.g. for dopamine or serotonin) and, once inside the cell, they create chemical reactions that kill it. A more recent approach involves toxins that bind to receptors on the surface of cells, allowing for even more specific targeting of particular neurons.
•Molecular genetic approaches: Optogenetics
GOALS
•Goal: make neurons express receptors that inhibit/excite the cell at will
Magnetic Resonance Imaging (MRI)
a technique that uses magnetic fields and radio waves to produce computer generated images that distinguish among different types of soft tissue; allows us to see structures within the brain.
TMS - benefits vs drawbacks
•Advantages of TMS
▫Excellent spatial and temporal resolution
▫Participant acts as own control
•Disadvantages of TMS
▫Can only affect surface regions
▫We don’t know how it works!
E.g. spatial extent
MRI vs CT (what do they look like?)
Principles of fMRI
•Oxygen in blood is carried by hemoglobin
▫With oxygen: oxyhemoglobin
▫Without oxygen: deoxyhemoglobin
•Active neurons result in greater influx of oxyhemoglobin
▫Changes local magnetic properties; fMRI detects this change
▫Blood Oxygen Level Dependent signal (BOLD)
▫
Why do we use blood to measure activity in fMRI’s and PET scans? What does blood tell us?
▫Neural activity consumes oxygen
▫Neurons get oxygen from the local blood supply
▫When neurons use more oxygen, more blood is pumped into the active region
•The time taken for this response is slow (several seconds) and so PET & fMRI have poor temporal resolution, but pretty good spatial resolution
•
What does fMRI stand for?
Functional Magnetic Resonance Imaging (fMRI)
What does Reverse Engineering do?
•Infer the function of a region (or cognitive mechanism) by removing it and measuring the effect on the rest of the system•
Functional Brain Imaging Techniques and what they do/ what are they good for
(PET, fMRI)
–image the brain activity in a dynamic fashion
–used to study changes in brain function
Compare Single cell / multi-unit recordings
EEG ERP NEUROIMAGING
DIRECT VS INDIRECT
SPATIAL AND TEMPORAL RESOLUTION
??????????
How do we use a PET scan to study cognition?
•Molecular genetic approaches: Optogenetics - PROS AND CONS
- Pros: Excellent temporal and spatial resolution
- Cons:
- Not good if you’re looking at something on a slower time scale
- Expensive, complicated
•
Temporal resolution
▫the ability to track the time-course of brain function
▫usually expressed in ms or sec
▫applies only to functional techniques
*** WHAT IS A VOXEL? WHAT CAN IT DO?
So if you can’t measure individual protons, what can you do?
Will bigger or smaller voxels give you higher resolution?
Smaller voxels: higher resolution
(SORT OF LIKE A 3D PIXEL?)
fMRI vs. PET in Temporal resolution
▫fMRI > PET
What is TMS?
Temporary Lesions in Humans
(cognitive neuropsychological approach)
Can a particular function be spared/impaired relative to other cognitive functions?
Addresses questions of what the building blocks of cognition are (irrespective of where they are)
fMRI
used to asses brain activity
Changes in properties of blood. Active nerve tissue (neurons) require more energy, oxygn, atp, blood flow,.
Basis of fMRI- Active neurons demand need more oxygen, blood
What are the Side-effects of TMS?
- Generally safe for people with no history of seizures
- Loud
- Can cause muscle twitches (uncomfortable)
What is an MRI ?
Magnetic Resonance Imaging
•MRI = a map of different behavior
•How/Why can we detect electrical activity of neurons on the scalp?
•
▫Synchronously active populations of neurons generate a large enough electrical field
▫
▫Not measuring action potentials; instead postsynaptic potentials in dendrites
▫
•Structural Imaging methods
▫Computerized Tomography Scans (CT)
▫Magnetic Resonance Imaging (MRI)
fMRI what is it?
What are the Key concepts in functional imaging
•Measures the moment-to-moment variable characteristics of the brain that may be associated with cognitive processes
PET Positron Emission Tomography (PET) scan
a visual display of brain activity that detects where a radioactive form of glucose goes while the brain performs a given task
elicited damage (example)
(e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
TMS - Interference
- Generally reduces performance (interference)
- Sometimes enhances performance (facilitation)
▫One region inhibits another
▫Several regions are competing
Example: Area V5, involved in
perceiving motion
*** What is an EEG
- Non-invasive: main electrophysiological technique in humans
- Electrodes placed on the scalp
- Measures summed electrical potentials
- from millions of neurons
•
- Note: electrical signals from a single neuron are too small to record non-invasively and can’t be distinguished from signals from other neurons.
- How/Why can we detect electrical activity of neurons on the scalp?
•
▫Synchronously active populations of neurons generate a large enough electrical field
▫
▫Not measuring action potentials; instead postsynaptic potentials in dendrites
▫
Lesion methods in nonhuman animals
- Aspiration
- Transection
- Neurochemical lesions
- Reversible “lesions”
fMRI vs. PET in Spatial resolution
▫fMRI > PET
•Neurochemical lesions
▫Pro: doesn’t damage white matter tracts
(Lesion methods in nonhuman animals)
MRI -?????????
•Looking at magnetic properties of hydrogen protons
▫Our bodies have lots of water, so lots of hydrogen, so lots of protons
•Under the influence of an external magnetic field and radio waves:
▫Protons behave differently depending on what kind of tissue they’re in (white/grey/CSF)
What type of scan is this?
CT (Structural imaging)
BRIEF SUMMARY OF THE LESION APPROACH
•Infer the function of a region or the existence of cognitive mechanism by removing it and measuring the effect on the rest of the system
•
•Disruption of brain function comes about through natural damage (strokes, etc.), elicited damage (e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
•
Cognitive Subtraction
•A region is “active” if it shows a greater response in one condition relative to another: cognitive subtraction.
Draw an example of an MRI
fMRI BOLD signal
BLOOD OXYGEN LEVEL DEPENDENT
hemoglobin with oxyegn- with oxygen-: much weaker local magnetic field, so effect of the global (MRI) magnetic field is stronger = BOLD signal
•Transection
Lesion methods in nonhuman animals
Involves cutting of discrete white matter bundles such as the corpus callosum (separating the hemispheres) or the fornix (carrying information from the hippocampus)
Limitation of human neuropsychology as a tool for cognitive neuroscience
•The extent of the brain damage varies across patients, and it is rarely confined to a single region, so it is often difficult to draw conclusions about the function of a brain area.
Advantages of MRI vs CT?
(explain)
•Advantages of MRI over CT
▫Does not use ionizing radiation
▫Better spatial resolution (e.g. folds of individual gyri)
MRI: ~1mm; CT Scans: 0.5 to 1 cm
▫Better discrimination between white matter and gray matter
•
(classical neuropsychology approach)
What functions are disrupted by damage to region X? Addresses questions of functional specialization by regions, provides converging evidence to functional imaging
cognitive subtraction
The idea behind cognitive subtraction is that, by comparing the activity of the brain in a task that utilizes a particular cognitive component (e.g. the visual lexicon) to the activity of the brain in a baseline task that does not, it is possible to infer which regions are specialized for this particular cognitive component.
•Functional Imaging (methods)
▫Positron Emission Tomography (PET)
▫Functional MRI (fMRI)
Transection
WHAT IS IT / HOW DOES IT WORK?
. This involves cutting of discrete white matter bundles such as the corpus callosum (separating the hemispheres) or the fornix (carrying information from the hippocampus).
- FMRI
- What is being measured/how it works
Hemoglobin, oxygenation, BOLD signal
?
What is Human Neuropsychology?
Neuropsychology: Study of human patients with brain damage
Looking at the effects of naturally occurring lesions
Lesions are NOT created for the purpose of doing research!
What are some reasons someone might have brain damage?
Stroke, tumor, traumatic brain injury, surgery
Neuropsychology in humans takes advantage of accidents
Stroke, tumor
Sometimes brain surgery
Not creating the lesions for the expressed purpose of studying its effects
Interested in what these lesions can tell us about the mind (cognition)
About how the brain works
About the relationship between cognition and the brain
Lesion Approach -
- Infer the function of a region or the existence of cognitive mechanism by removing it and measuring the effect on the rest of the system
- Disruption of brain function comes about through natural damage (strokes, etc.), elicited damage (e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
•
Principles of fMRI vs MRI
- Basic physics same as structural MRI
- Structural MRI:
▫Looking at differences in behavior of protons that depend on the tissue the proton is in
•fMRI:
▫Looking at differences in behavior of protons that depend on whether the proton is in oxygenated or deoxygenated blood
•
MRI disadvantages
- Expensive
- Metal Implants & Pacemakers are all contraindications for MRI scanning
- Claustrophobia
- Loud
- Can’t move
What is behavioral Neuroscience?
Neuropsychology in non-human animals
hemoglobin with and without oxygen( deoxy)
hemoglobin-containing oxygen-transport metalloprotein in the red blood cell
without oxygen- creates a local magnetic field which disturbs the global magnetic field
with oxygen-: much weaker local magnetic field, so effect of the global (MRI) magnetic field is stronger = BOLD signal
radio frequency pulse
is applied that knocks the orientation of the aligned protons by 90 degrees to their original orientation.
As the protons spin (or precess) in this new state they produce a detectable change in the magnetic field and this is what forms the basis of the MR signal. The protons will eventually be pulled back into their original alignment with the magnetic field (they “relax”).
TMS - How it works
Temporary Lesions: Transcranial Magnetic Stimulation
- Non-invasive focal stimulation of the brain
- TMS coil creates a magnetic field
- Induces a current in nearby neurons
- Disrupts ongoing activity
- Effects are generally subtle
- Generally safe for people with no history of seizures
- Loud
- Can cause muscle twitches (uncomfortable)
Pros / Cons of TMS?
•Advantages of TMS
▫Excellent spatial and temporal resolution
▫Participant acts as own control
•Disadvantages of TMS
▫Can only affect surface regions
▫We don’t know how it works!
E.g. spatial extent
Excellent temporal resolution: pluses only last a few milliseconds
Natural lesions are large: may affect several cognitive processes, hard to tease them apart
Spatial resolution of TMS: 1 cm2
Can only affect surface regions:
Lots of areas we’re interested in are underneath the surface: hippocampus for memory, amygdala for emotion, orbitofrontal cortex
Spatial extent: you think you’re lesioning a region just under your TMS wand, but possibly you’re affecting distant brain regions that are connected to the site
Remember, this is a stimuluation technique
natural damage (example)
(strokes, etc.)
Reversible “lesions”
▫AKA inactivations
Reversible “lesions.” Pharmacological manipulations can sometimes produce reversible functional lesions. For example, scopolamine produces a temporary amnesia during the time in which the drug is active. Cooling of parts of the brain also temporarily suppresses neural activity.
•Behavioral neuroscience - What is it? why is it good/important?
= cognitive neuroscience in non-human animals.
•
•Animal models are important for testing hypotheses in ways that can’t be (or can’t be easily) done in humans
•
•Animal models are good for “before” and “after” designs – the animal is its own control
Process X vs Process Y (cognitive subtraction)
Two Traditions of Human Neuropsychology
(classical neuropsychology approach)
▫Addresses questions of functional specialization by regions, provides converging evidence to functional imaging
(cognitive neuropsychological approach)
▫Addresses questions of what the building blocks of cognition are (irrespective of where they are)
•Disruption of brain function comes about through:
natural damage (strokes, etc.), elicited damage (e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
Functional Imaging methods
fMRI, PET
Lesion methods in nonhuman animals
•Molecular genetic approaches: Optogenetics
WHAT ARE THE STEPS? PROS? CONS?
Step 1: viruses hijack your cells and make them express proteins
- normal viruses: make your cells make more viruses
- these viruses: make neurons create special receptors
Step 2: inject virus into the brain
- virus hijacks the cell, makes it create those receptors
•Step 3: Activate the receptors
▫Optogenetics: receptors activated by shining a laser on them
- Step 4: Receptors inhibit or activate the cell
- Pros: Excellent temporal and spatial resolution
- Cons:
- Not good if you’re looking at something on a slower time scale
- Expensive, complicated
Optogenetics:
Channels taken from algae, open in response to light
Step 4: different receptors to inhibit or excite the cell
▫
Types of imaging?
Structural: studies brain anatomy. (CT, MRI)
Functional: imaging studies brain function (activity). (fMRI, PET)
What is being measured in an fMRI ?
What is being measured in a PET scan
▫fMRI: blood oxygenation
▫PET: blood flow in a region
What is ERP?
Continuous recording of electrical activity in the brain
Event-related potentials (ERPs)
What do Functional imaging methods measure
•Functional imaging methods (fMRI, PET) do not measure neuronal activity (e.g. action potentials) directly
▫Instead, measure metabolic activity of neurons
▫Assumption: more active, higher metabolism
▫Functional imaging provides indirect measures of neuronal activity
•But: brain has a constant supply of blood and oxygen
▫Brain is “active” all the time!
WHAT IS THE LESION METHOD?
cognitive neuropsychological approach
(2) Can a particular function be spared/impaired relative to other cognitive functions? (cognitive neuropsychological approach)
▫Addresses questions of what the building blocks of cognition are (irrespective of where they are)
What are the Effects of TMS?
- Generally reduces performance (interference)
- Sometimes enhances performance (facilitation)
▫One region inhibits another
▫Several regions are competing
Example: Area V5, involved in
perceiving motion
Damage to V5 results in motion blindness: seeing the world as a series of freeze frames
TMS - Facilitation
•Sometimes enhances performance (facilitation)
▫One region inhibits another
▫Several regions are competing
Example: Area V5, involved in
perceiving motion
What do we assume about blood flow when studying cognition via PET scans?
Assumption: More blood flow in active areas = more radioactive tracer = more positrons emitted. PET is a relative measure.
Functional imaging studies what? with what methods?
Functional: imaging studies brain function (activity). (fMRI, PET)
Using PET to study cognition - what does this actually look like
Voxels / Resolution
•Dimensions of voxels gives you the resolution of your scan
fMRI vs. PET in •Invasiveness
▫fMRI: Non-invasive
▫PET: Invasive
WHAT IS FUNCTIONAL IMAGING?
Functional imaging is based on the assumption that neural activity produces local physiological changes in that region of the brain. This can be used to produce dynamic maps of the moment-to-moment activity of the brain when engaged in cognitive tasks.
Classical neuropsychology approach
(1) What functions are disrupted by damage to region X? (classical neuropsychology approach)
▫Addresses questions of functional specialization by regions, provides converging evidence to functional imaging
TMS - CONTROL CONDITIONS
•“Sham” TMS: hold coil over head
▫Not so good: does not control for noise, twitching
- TMS stimulation in a non-critical region
- TMS stimulation in a non-critical time period
CT Scans - Spatial Resolution?
•Spatial resolution is ~ .5 to 1 cm; difficult to distinguish gray/white matter
- PET
- What is being measured/how it works
?
VERY IMPORTANT FMRI VS PET !!
INVASIVENESS
SPATIAL RESOLUTION
TEMPORAL RESOLUTION
??? AND WHY????
PET SCAN
what is it?
The importance of lesion studies
•Functional imaging can’t tell us whether a brain area is necessary for a task
▫Correlation is not causation
•Lesion data allow for a stronger inference of necessity/causality
Have people do a task in the fMRI scanner
See a bunch of brain activations relative to a control task
Can we conclude that those areas are necessary for the task?
Think of a play
If the leading man gets sick, the play can’t go on
He is necessary for the show
Now think of a stage hand
He’s involved in the play
But it can go on even if he’s sick
He’s involved in the play but not necessary for it
A region might be active because of a particular strategy that a participant adopted
But there could be other strategies that would also work
Musical analogy: one of the ushers calls in sick; can get a different usher, or maybe people can find their own way to their seats
What type of scan is this?
MRI (Structural imaging)
Spatial Resolution
•Spatial resolution
▫the minimum distance at which two separate structures can be distinguished
▫usually expressed in mm▫applies to both structural and functional techniques
When do we use CT scans?
•Mostly used in medical contexts
WHAT IS TMS?
Transcranial Magnetic Stimulation (TMS)
Structural Brain Imaging Techniques and what they do/ what are they good for
(CT scans, structural MRI)
•Structural (CT scans, structural MRI)
–image the different anatomical structures inside the brain in a static fashion
–ideal for identifying the presence of tumors, hemorrhages etc.
–individual/clinical differences
What Does it Mean to Say a Brain Region is “Active”?
•What to do?
▫Compare RELATIVE differences in brain activity between two or more conditions
•A region is “active” if it shows a greater response in one condition relative to another: cognitive subtraction.
•
How does Reverse Engeneering work?
•For example, if damage to a region disrupts reading, but not speaking or seeing, then one might conclude that the region is specialized for some aspect of processing text
•
•Disruption of brain function comes about through natural damage (strokes, etc.), elicited damage (e.g. animal models), or harmless temporary changes induced electro-magnetically (TMS)
•
Computed Tomography (CT) scan
series of x-ray photos taken from different angels and combined by computers into a composite representation of a slice through the body.
What do CT scans look like?
- X-ray absorption is correlated with tissue density (bone > tissue > CSF)
- High-density regions light colored; low-density dark colored
HOw MRI works
- We apply a magnetic field to make protons spin in the same angle.
- We apply radio-frequency (RF) energy to tilt them a little.
- We let them relax - they give off energy
- Different tissues and fluids give off different patterns of energy
- We measure the energy from different angles, which tells us what tissue/fluid is in a given point in space.
- We assemble all the points to make a 3-D image
Structural Imaging (methods)
CT, Structural MRI
Functional MRI (fMRI)
a technique for revealing blood flow and, therefore, brain activity by comparing successive MRI scans. MRI scans show brain anatomy; fMRI scans show brain function`
What do/can Voxels do?
•Cannot detect signal from individual protons
▫Must average signal within a volume of the brain
How do PET and fMRI measure neural activity?
- Measures the moment-to-moment variable characteristics of the brain that may be associated with cognitive processes
- PET and fMRI indirectly measure neural activity
▫measures changes associated with energy use
•PET and fMRI are relative measures and require comparison
▫Cognitive subtraction (Experimental – Control)
CT SCANS - what do they do? how do they work?
Pros / cons
- Based on X-ray methods
- Minimally invasive
- Regular x-ray: 2-dimensional image of a shadow
- X-ray is absorbed by bone
- Casts a shadow that is recorded
- CT takes several of these 2-D images, reconstructs them into a 3-D image
