Neuroimaging

Question 1

X-ray- general description

Answer 1

• gives a course description of body
• x-ray tube fires x-ray, pass through body. opposite side of body is a film that captures the energy –> image
• x rays absorbed at different levels by different tissues

Question 2

X-ray pro and cons

Answer 2

Cons: low quality/resolution

• single image doesn’t give much info on brain
• no info on moment-moment activity

Pros:idk lol

Question 3

Cerebral Angiography

Answer 3

Contrast x-ray

• contrast = dye that absorbs X-rays at different amount (most common is iodine
• iodine absorbs X-rays at much higher level. it is injected into blood stream- gives you map of arteries in brain
• gives info about blood flow (stroke)

Question 4

Pros and cons of angiogram

Answer 4

pros: done everywhere, with limited resources
cons: doesn’t show tissue, only vessels. not done for healthy people- risks

Question 5

Computed Tomography (CT)

Answer 5

• variation of X-ray
• same idea: firing x-rays but they are received by digital receiver on the other side
• fired multiple x-rays instead of 1, and fire from multiple angles and compile it together
• lots of low resolution images, reconstruct into 1 better image
• 1970s
• relatively uncommon now
• improved images by -reconstruction

Question 6

Pros and cons of CT

Answer 6

pro: improved x-ray image. first time separate difference btw fluid and brain. (valuable in stroke to see tissue loss)
- good for seeing large vesicle, lesions, brain size
cons: radioactive waves, not ideal for looking at brain in multiple sessions, exposure to radiation
- can’t see difference btw white and gray matter
- only as good as its algorithms (improved a lot since 70s)

Question 7

MRI

Answer 7

• 1940s
• H atom has magnetic resonance (N and S pole), under strong magnetic conditions, H atoms align themselves
• then, perturb magnetic field, as they revert back, they release energy. measure this energy. different densities of H20 throughout body = different energies. energy measured by tube around you

ubc has 3 T and 7T (At 3T, it is 60,000x earth’s magnetic field)

Question 8

MRI pros and cons

Answer 8

pro: amazing brain image, reconstruction of many slices = 3D image
- non invasive, no harm

cons:

Question 9

Overlay plot

Answer 9

• pictures from multiple individuals who have similar symptoms
• find common areas that are damaged
• gives idea what regions are important for that loss of function

Question 10

Diffusion Tensor Imaging (DTI)

Answer 10

• structural
• variant of MRI
• relies on how water molecule move in brain (algorithm)
• shows white matter
• water molecule in axons are limited to where they can move, algorithm looks for constrained water

Question 11

pros and cons of DTI

Answer 11

pros: see white matter, in a number of conditions there is no obvious change in gray matter, but may see differences in white matter (ex: Arcuate fascicules: tracts of white matter that connect Broca’s are to Wernicke’s)

Question 12

Electroencephalography (EEG)

Answer 12

• measure voltage changes on scalp, reflects neuronal activity
• usually 20-60 electrodes on scalp, any one can be picking up signals from thousands- millions of neurons
• course measurement of brain activity

Pros: fast, almost real time, easy, non-invasive, measure combo of muscle and brain activity

Cons: course measurement

Question 13

describe neuron activity when going from awake from asleep

Answer 13

neurons fire less often, but more in synch with each other. greater amplitude and decreased frequency.

• delta waves = deep sleep, slow
• gamma waves = high frequency, working on intense mental activity

Question 14

most intense brain waves

Answer 14

gamma in meditating monks woowwww

Question 15

Positron Emission Tomography (PET)

Answer 15

• *functional
• uses radioactive ligand (i.e. cocaine, FDG) which will bind and decay -> positrons are emitted. they collide with electrons in the brain, and photons are produced, exit the head and are detected
• active areas of brain use more blood and thus have more radioactive labels

Question 16

Cyclotron

Answer 16

creates radioactive molecule

Question 17

FDG (fluorodeoxyglucose)

and cons to using it

Answer 17

• radioactive glucose
• brain areas that are more active need more glucose
• see stronger signal in these areas, gives baseline activity in brain

Application: in schiz the front of brain has less FDG than healthy

• indirect measure of brain activity
• scans are 45 min, how meaningful is 1 image to represent all that activity
• not good temporal resolution
• spatial isn’t great either

Question 18

Mean difference images

Answer 18

Simulation-Control = Difference
- add up all individual difference images to get 1 mean

• individual does a task, and then control (rest)
  issue: all individual differences are slightly different. sometimes average isn’t the same as any individual
• done in PET and fMRI

Question 19

PET cons

Answer 19

• expensive
• temporally slow
• poor spatial resolution

Pro:
useful for looking at specific systems (i.e. cocaine binds to areas involved in dopamine transmission, can see exactly where dopamine neurons are using pet- shown that dopamine system gets weaker throughout lifetime in drug addicts (all addictive
drugs))
- useful for looking at specific proteins (i.e. tau)
- useful for looking at lifespan/condition changes (stroke, maybe CTE)

Question 20

Diaschisis

Answer 20

Loss of function in part of brain that normally gets input/output from a region that has been damaged

• seen with PET

Question 21

fMRI

Answer 21

• early 1990s, discovered oxygenated and deoxygenated blood have different profiles
• as balance of deoxygenated vs oxygenated blood changes, you can measure that
• presumption: active regions need more oxygenated blood
• functional image laid on top of structural

== BOLD response (blood oxygen level dependent)

Question 22

BOLD response: what is happening at the synapse?

Answer 22

• synapse is v active, needs energy therefore more oxygen
• oxygen comes from blood (astrocytes)
• astrocytes have glutamate receptors on them. when you activate these receptors, it causes dilation of blood vessels due to influx of Ca2+ allowing more oxygenated blood to the area
  (more blood given than actually need)

Question 23

Paired Image Subtraction

Answer 23

• 2 similar conditions (experimental and control)
• subtract control from experimental
• any overlapping brain activity is removed
• leave behind construct of interest

*quality of results will be directly related to quality of controls

Question 24

Problems with interpreting fMRI studies (5)

Answer 24

1. Spatial Averaging- (one trial you see tea pot, then you see it again. Presumed that brain activity would be same- maybe its not. Also spatial averaging over subjects- BUT all our brains are different sizes. So brains are squished into brain mold. Might run into epiphenomenon: you get an average result. But maybe that average doesn’t reflect any one individual. Analogy = books in your office on left wall and right wall, average book is in centre of room, but there are none in the middle
2. Spatial resolution: under 3 mm for voxel= 3D equivalent of a pixel. Not capturing single brain cell activity
3. Temporal resolution: At time 0, stimulus is presented (i.e. we see the teapot), we see BOLD response 6-7 seconds after. This means that we’re recording activity of things that happen earlier in time. Since brains are always active, this is a problem. At its tightest resolution, it is still on the order of seconds. Hard to distinguish bursts of activity within a second (we can get 500 or more AP a second)
4. Not necessarily necessity: There are many brain areas that don’t necessarily show up on a BOLD that are very important. Many do, but are not as important as they seem. For example, language tasks show bilateral activity, yet we know that left hemisphere is mainly controlling language.
5. Focus on increases in activity: the presumption is that if a brain area is important, It receives more oxygenated blood. BUT some areas just receive a lot of oxygenated blood all the time, i.e. the HPC has high level of oxygenated blood all time.
   ○ Some researches noticed, When patients went to relax, huge burst of BOLD. Probably because people were thinking a lot about other things, mind wanders. This lead to new approach….. Resting state functional connectivity MRI

Question 25

The default mode network

Answer 25

- studied because of problem 5! ( some regions are more active at rest than during task) - resting state functional connectivity MRI - choose 1 region as seen region, every time activity in it goes up, see what other brain regions also do - when BOLD goes down, see what else goes down - no task given default mode network: ○ Seen when mind wanders, not working on a task, thinking about what you want to do ○ Medial PFC, left and right inferior parietal, posterior cingulate (autobiographical thoughts), and medial temporal lobe (Sometimes)

Question 26

Problems with interpreting fMRI studies (6-10)

Answer 26

6. Regional hemodynamics: BOLD response graph isn't universal. Looks different for certain brain areas. 7. Confounds: anxiety, boredom: scanner is not a neutral space. Scanner is anxiety-provoking. Loud sound. If you are tired, you might sleep and twitch 8. Confounds: drugs: i.e. coffee. Change how brain functions - shows up in BOLD in ways that are hard to predict 9. Anticipatory hemodynamics: when you make someone do a task many times in a row, you start to anticipate the demands/what you will have to do. Brain anticipates what areas will need oxygenated blood, so they will get it before the regions are even active 10. Reliability: main point: from one scan to another, you don't get the same data. Recent meta-analysis did task and re-task, reliability was about 30%. 11. Statistic: in a brain image, there are between 60,000 and 1,000,000 voxels depending on the scanner. Each one for your control vs experimental is basically a t-test. Normally, significance threshold is t= 0.05. (19/20 times your observation is correct). 5% of million is A LOT of false positives/negatives. It's not stringent enough. To get around this is use a more stringent value. We've known this for years in fMRI, but didn’t do it (even today this happens in literature). A post-doc in Halifax put a salmon in a scanner, asked the salmon to look at pictures, rate emotions. When he performed the analysis. And during the emotional pictures there was emotional significance. (2011)

Question 27

Stages of Consciousness

Answer 27

1. Brain death: all functions of brain and brain stem have permanently ceased 2. Coma: loss of consciousness is complete: cycles of wake and sleep disappear, eyes are closed. Usually temporary (2-4 weeks). Afterward, patients emerge into consciousness or one of the other states. 3. Vegetative state: sleep-wake cycles, eyes may open to stimulation. Only behaviours displayed tent to be reflexive 4. Minimally conscious state: patient may seem vegetative but shows signs of awareness, such as following a command, reaching for something. Locked- in syndrome: (technically not a disorder of consciousness, because patients are fully conscious) but they cannot move and may be mistakenly deemed vegetative or minimally conscious. Many retain ability to blink/move eyes.

Question 28

Summary of Adrian Owen's paper

Answer 28

PET scan (Positron-emission tomography) • Put girl in vegetative state in PET scan and showed pictures of family/friends to look for signs of response • Saw her brain responded similarly to how healthy individuals To answer what this meant, years of research Covert Consciousness = Hidden awareness in patients who are declared vegetative Then, researches sedated group of healthy participants and exposed them to same combo of speech and non-speech sounds that elicited normal pattern of brain activity in vegetative patients. - Healthy subjects were unconscious, and there speech perception part of brain were activated just as strongly as when conscious - This proved that "normal" responses to speech was unreliable indicator of covert consciousness Next, they set out measuring brain activity while healthy participants did tasks like singing, walking, playing tennis. Mentally performing these tasks generates reliable pattern of activity similar to actually performing it. - Used fMRI (which doesn’t require injection of tracer chemicals like PET does) discovered imagining playing tennis and walking room -> room in house elicited strong activity in premotor cortex (tennis) and parietal love and parahippocampal gyrus (room) - This technique worked when tried on first vegetative patient - Worked for 17% of patients tried - Suggest higher level of processing in vegetative patients than originally thought also used EEG, but didn't get good resolution. tasks were adaptive to produce activity on cortex What now? - Use of fMRI and EEG to detect awareness and communicate with non-responsive patients paves way for development of brain-computer interfaces ○ Translating specific thoughts into concepts for those with brain injuries Also brings up ethical dilemnas: can you ask a patients If they want to continue living? Do they have the capactiy to answer that