Lecture 2/3: the nature of brain lesions

Question 1

Brain tumors

Answer 1

• Cancerous growth inside the brain
• Glioma: tumour from the gial cells (most tumors)
  → in the brain, can distort the brain
• Meningioma: tumor from the meninges (layers that protect the cortex)
  → meningiomas are outside of the brain (between the skull and brain).
  → 3 layers of tissue:
  - Dura matter
  - Arachnoid
  - Pia matter
  These are layers that act with cerebrospinal fluid as a protective effect. Layers made of cells, tumors like these push on the brain and cause defecits because it can affect the function of the brain its pushing on.
  → tumor that grows between the skull and brain
• Brain tumors, even if they’re not in the neurons, they can affect the neurons, they can disrupt the connectivity between the two brain areas and they can also affect the region where it grows.
• Brain tumors are not useful to study the brain function because they grow very fast, so the person will have new deficits every day so it is hard to study to associate a brain function with the region where the tumor is since it is constantly evolving.
• Can still affect or destroy the neurons in the region where the tumor grows.
• Can also destroy axons (destroy connectivity)
• Can push the brain into the skull or away
• Depending on the type of tumor (I,II,III,IV) more or less useful to study. If it is growing fast (III, IV), new problems every day = hard to study

Question 2

Strokes

Answer 2

Interruption of blood supply in an area of the brain. Neurons can’t function without oxygen and the blood vessels bring oxygen to the neuron.

Question 3

What are the two types of strokes?

Answer 3

Ischemic stroke
* Obstruction by a blood clot (blocks a blood vessel). Slows down the blood circulation or completely blocks it
* The blood flow is cut-off in that brain area (local). This can cause behavioural deficits.

Hemorrhagic Stroke
* Sometimes a defect in membrane thickness of a blood vessel.
* Causes an aneurysm
* Can burst: bleeding inside the brain

Question 4

Blood supply to the brain

Answer 4

Middle cerebral artery:
- along the sylvian fissure
- a lot of branches
- supplies the lateral surface: frontal, parietal, temporal (part)
- covers most of the lateral surface
- does not cover occipital lobe
- tan had a clot in this branch that innervates the frontal part (IFG)
Anterior cerebral artery (ACA):
- supplies the upper part and the medial surface of the frontal and parietal lobes
Posterior cerebral artery (PCA)
- Supplies the occipital areas and part of the temporal lobe (medial surface of temporal lobe and all of occipital lobe)

Question 5

Head injuries (trauma)

Answer 5

Traumatic Brain Injury (TBI)
* Sudden change to the brain caused by a violent blow or jolt to the head

Can be:
1. Open trauma or closed trauma
2. Focal (very localized): penetrating wound, open fracture, laceration, hematoma (bruise at specefic location), contusion
OR
Diffuse (affect a much larger part of the brain): Concussion, axonal lessions

Question 6

Phineas Gage case

Answer 6

• Patient had bad injury to the frontal lobe (penatrating wound)
• a lot of frontal deficits
• Broken skull that can push on a focal part of the brain and cause damage

Question 7

Diffuse Axonal Injury

Answer 7

• Diffuse axonal injury is one type of diffuse brain injury
  → breaks a lot of axons, so different brain areas can’t communicate with one another (even the brain stem → responsible for a lot of survival functions)
• Other types: hypoxic brain swelling, brain swelling, vascular injury
• Can happend when head is rapidly accelerated. Ex: car accident, shaken baby syndrome
• Carbon monoxide poisoning = destroy part of the brain/ usually not focal
• Often causes unconsciousness and vegetative state.

Question 8

Disconnection Syndrome

Answer 8

• Injuries to the white matter
• Connection between two areas are damaged (so they work independently)
• Closed head trauma (CHT) can affect white matter by:
  - Shear and stretch forces tha distort the axons
  - Vascular disruption and edema (problem with blood income to white matter area)\

Question 9

White matter abnormalities

Answer 9

• Congenital Agenesis of the Corpus Callosum
  → Corpus callosum does not generate in babies
• Callosotomy
  → Surgeon (usually for epilepsy or remove tumor)
  → Causes disconnection syndrome called split bain patient = they have two independent hemispheres
• Baby born without a corpus callosum does not have the same effect then when section it in adults (babies without CC = almost no effect because happens early)

Question 10

Perinatal stroke example

Answer 10

• 13 year old with motor deficits, motor weakness on his right side. Overall was a normal teenager.
• Missing 25% of his cortex → has a stroke as a baby but living his life normally,
• Brain can completely reorganize itself when it happens early in life.

Question 11

Epilepsy

Answer 11

• Abnormal discharge in a part of the brain and extends to other parts
  1) Partial Seizures (focal seizures)
• Simple Partial Seizures
  → dysfunction of very specific area
  → focal abnormalities, local symptoms in somatosensory, vision, audition, olfaction
  → symptoms are local + temporary
• Complex Partial Seizures
  → affecting more than one brain area
  → effects on more complex cognitive functions
  → frequently: symptoms of disruption of higher mental functions

2) Unilateral Seizures
* abnormal electricity discharge spread over wide area in one hemisphere (can even spread on the other hemisphere).

Question 12

Epilepsy Treatment

Answer 12

• Most of the time epilepsy is treated with medication = antiepileptic (milder cases)
• When medication does not work there is another option: brain surgery

Question 13

Steps taken before brain surgery to treat epilepsy

Answer 13

1) Find the foyer first: Electroencephalogram → EEG to find where there is abnormal electrical activity.
2) Neuropsychological testing to see what is the effect of the epilepsy in the person.
* Memory (verbal memory, memory for faces…)
* Language
* Executive functions (ex: Wisconsin test)
→ use a baseline measure in order to be able to compare after surgery.

Surgeon knows exaclty what brain area was removed → allows them to associate new deficits that patient has with the region removed from the brain.

Question 14

Brain surgery

Answer 14

• Importance of localisation and sulci
• Penfield and the Montreal Procedure (1930s) to localise functions and know what to remove and what not to remove to try to preserve functions.
• Under local anaesthesia, you can ask the patient to speak while you stimulate different brain areas. Ex: stimulate a region to see what areas cause speech arest. Stimulate a region: stop speaking = temporary lesion.

Question 15

Modern Presurgical Mapping

Answer 15

fMRI to localise brain functions in each individual
→ Sometimes the brain can be distorted by a lesion or tumor (disrupt where the differnt functions are).
→ functional reorganisation: reorganisation around the tumor or lesion that someone had in the past which can make the localization of a specific function different in each patient. This is why we use fMRI to map.

Question 16

Animal studies

Answer 16

Possible to remove exactly the cortex you want to study without touching the axons underneath or adjacent brain area (white matter regions).

Question 17

Functional Magnetic Resonance Imaging (fMRI)

Answer 17

• See specific brain areas that are responsible for specific functions.
• Functional neuroimaging technique → see what brain areas are active during a task.
• Spatial resolution > Temporal resolution
  → Precise in terms of spatial resolution (can even see subcortical activation) but the temporal resolution is not as good.
• Measures changes in blood consumption in brain areas where neurons are active → the BOLD signal.

The idea is that more active areas in the brain require more blood for glucose and oxygen consumption.
→ Oxygenated iron in the blood has different magnetic properties compared to deoxygenated iron. Therefore, we can measure changes in the blood flow by using the properties of oxygenated vs. deoxygenated iron.
→ BOLD signal (Blood Oxygen Level Dependent)
→ Remember, this technique is not a direct measure of neuronal activity! It is an INDIRECT way of measuring neuronal activity.
→ Does not measure electrical activity of the neuron. Measures change in blood vessels that bring oxygen to the neuron.

Question 18

Magnetic Reasonance Imaging (MRI)

Answer 18

• Fixed picture of the brain.
• Allows you to study the anatomy of the brain in vivo.
• Involves the use of magnetic field to image the brain
• There are different types of images depending on your research question and the image acquisition parameters that will be used
• Standard for looking at the morphology of the brain is using T1-weighted structural images: the cortex appears darker than the white matter
• The strength of the magnet determines your spatial resolution (1.5Tesla, 3Tesla, 7Tesla)
• Stronger magnet = stronger spatial resolution

Image the Grey matter:
- allows you to study the effect of learning or expertise. Ex: patient does a scan and then they have to learn a motor task for several weeks. So you can see if there is a change in the grey mater after learning this task.
- Look at anatomy of specific brain areas and group differences. Ex: Cortical thickness, overall volume of cortex, voxel-based morphmetry (density), gyrification.

Image the White matter:
- Structural MRI.
→ see white matter in structural image, but you can’t really see the connections so it justt looks like white matter (see integrity of white matter).
- Diffusion MRI
→ whole brain: identify areas where differences in white matter propreties.
→ Tractography: see white matter tracts that connect different brain areas.

Question 19

Resting State fMRI

Answer 19

• Measuring brain activity ‘at rest’ (they’re awake just chilling)
• The functional activations are overlaid onto structural MRI images for anatomical context. The functional activations are illustrated as heat maps – regions in red are the most active, and as you move away from the areas in red you have less and less activity.
• From a resting-state fMRI, we can see that the brain is active all the time.
• Function brain regions are organized as neworks (some regions are closely correlated in terms of brain activation)

Resting State fMRI allow us to study:
- study networks
- connectivity
- withing a network
- from a specific seed to the rest of the brain
- extract connectivity values from two specific brain areass.

Question 20

Task-based fMRI

Answer 20

measure changes during a specific behavioural task compared to a control task.
* Have participants do something specific and then localise where the activity is in the brain (where the person has dysfunction).
* Localisation of activations/functions
* Can extract very specific functions: example face perception, processing speech in noise.
* Can study development (longitudinal studies)

Question 21

Seed-based resting state connectivity

Answer 21

• Use a Specific Region of Interest (ROI) as a seed:
  → See wha other brain areas are connected (correlated activity) with the seed.
  → Group differences, effect of learning …

Ex: ask the software to show the intrinsic connectivity in a group of individuals between the posterior temporal area. For example, if you have a group of speech delay children, maybe their posterior language comprehension area is intrinsically less connected to other parts of the brain so the disconnectivity is associated with their symptoms.

Question 22

What is the main resting state network?

Answer 22

The main resting state network we hear about is the default mode network.
→ This network shows what brainn regions are active by default
→measures the connnectivity between the different network (which communicate together)
→Intrinsic connectivity: 2 regions that are always active at the same time at rest.

Question 23

What is needed for task-based fMRI:

Answer 23

What is needed for task-based fMRI:
* Need a task (can be passive or active)
→ ex: do a reasoning task, watch a movie
* Need contrasts/control conditions
→ need to contrast your condition of interest with another condition to remove the baseline noise of the brain (aka the brain activation that you have all the time, that everyone has).

Question 24

fMRI contrasts

Answer 24

Example:
Phonological working memory task
* auditory component (listening to words)
* Memory component (task)
* Baseline (fixation cross)

Question 25

What questions can you answer using fMRI?

Answer 25

• Study the normal brain: localize functions
• Study the functional effect of lesions: do the functions of a specific individual change in location because of their brain injury.
• Presurgical mapping → useful for neurosurgeons to have a map of brain
  activation for the specific patient they are working on before surgery
• Compare groups of people (ex: compare a group of individuals who speak english vs mandarin and see if they use brain inury)
• Study the effect of learning (Time 1 versus Time 2) → what happens in the brain when someone does a motor test.

Question 26

The autistic brain

Answer 26

Example: The autistic brain works differently
- We had an autistic group and a typically developing group - boh doing the same task.
- Reasoning task
- Increased visual activation autism: Enhanced visual processing
- The performance at the task was exactly the same, the autistic participants were as good as the controls but they recruited different brain areas to complete it

Question 27

Learning study

Answer 27

Example: Learning study
- Monolingual English speakers (L1)
- Enrolled in an intensive French (L2) class
- Did the same task at Time 1 and Time 2, in their first language (L1) and their second language (L2)

Contrast:
- Can either compare the two languages, or
- Compare Time 1 versus Time 2

Question 28

PET Scan

Answer 28

• Not used as much especially for research (it is invasive).
• Inject radioactive substance in the blood that emits positively charged particles (positrons)
• Measure variations in blood flow (by detecting the positrons) associated with cerebral functions. See the intake of the radioactive substance in specific areas of the brain.

Question 29

EEG

Answer 29

EEG (Electroencephalography)
- Place electrodes on the skull (non-invasive)
- Detects variation in electrical potential (measures electrical field) emitted by groups of neurons
- Very good temporal resolution (can see where the brain activation is in terms of milliseconds), but NOT spatial (cannot see which gyrus is being activated)
- can move while using EEG (unlike MRI)

Question 30

MEG

Answer 30

MEG (Magnetoencephalography)
- Measures magnetic field of what the current does
- Better spatial resolution
- Very good temporal resolution (compared to fMRI)
- expensive to run, not used as much

Question 31

Spatial resolution vs temporal resolution of each technique

Answer 31