Lecture 4: Clinical Research Techniques Flashcards
What are the clinical methods of investigation in neuroscience?
- Clinical history and examination
- Neuropathology
- Imaging
- Electrophysiology
- Chemical studies
What information will be achieved with a Clinical History?
Information about whether it is a targeted or specific problem
What is a Clinical examination?
Systematic assessment from brain to muscle
Who pioneered the standardized neurological examination?
Charcot
What did Charcot standardize?
The order that tests are done and the order in terms of problems in the brain, spinal cord
What is impairment in the brain or spinal cord usually due to?
Upper Motor Neurons
Where do UMNs have their cell bodies and axons?
UMNs usually have their cell bodies in the cortex and have long axons that go down to different spinal levels to connect with LMNs
What six things does a neurological exam assess?
- Mental status
- Cranial nerves
- Motor examination
- Sensory examination
- Cerebellar function
- Deep tendon reflexes
Which part of the NS is Mental Status a part of?
Central
Which part of the NS is Cranial Nerves a part of?
Central
Which part of the NS is Motor examination a part of?
Central and Peripheral
Which part of the NS is Sensory examination a part of?
Central and Peripheral
Which part of the NS is Cerebellar function a part of?
Central
Which part of the NS is Deep Tendon Reflexes a part of?
Central and Peripheral
Which scale assesses wakefulness?
The Glasgow coma scale
What assesses Cranial Nerves 2 and 3?
Shining a light in someones eye and seeing the pupil change
What is the direct response to testing cranial nerves 2 and 3?
When flashing the light in one eye the constriction of the pupil occurs in that eye
What is the consensual response to testing cranial nerves 2 and 3?
When flashing the light in the opposite eye the other pupil still constrics suggesting syncitimus activity
What does increased reflex suggest?
There is UMN lesions
What does decreased reflex suggest?
There is LMN lesions
What is Clonus?
Sustained contration
What does Clonus suggest?
UMN injury
What is normal in the Babinsky test?
There is flexion of the toes
What suggests an UMN injury with the babinski test?
Toes fanning out
What tests are used to test Deep Tendon reflexes?
- Lower extremity reflexes
* Babinski test
After determining an UMN lesion, what is the next step?
To determine where the UMN is injured
What can help identify where an UMN lesion is?
A neurological examination
What can a history of the progression of the symptoms indicate?
What the disease is
What is damage to the left frontal cortex associated with?
Difficulty speaking
What did Broca’s area establish?
The lateralization of linguistic function to the left hemisphere
What can pathology do?
Help confirm the clinical diagnosis
Where can Tau proteins often be seen?
In the brains of people with chronic traumatic encephalopathy
Why is imaging preferred over pathology?
Because pathology requires a sample which is more invasive and damaging
What is a CT Scan?
A series of X-ray slices
What are the advantages to CT?
- Cheap and fast
- Very common
- Good at detecting blood
What are the disadvantages to CT?
- Limited resolution
* Can miss acute stroke lesions
How does an MRI work?
Uses radio frequencies that excite tissues inside the brain and a magnet that records the picture
What are the advantages to MRIs?
- Provides very fine details of anatomy
* Multiple sequences can be used to detect specific problems
What are the disadvantages to MRIs?
- Takes an hour (vs 3 min for CT)
- Children require sedation and special care
- Expensive
- Availability limited
What was one of the first applications of MRIs?
Volume measurement
What do the brains of people with Alzheimer’s look like under an MRI?
The brain is small in general and the hippocampus is quite small
What are two types of MRI sequences?
- Diffusion weighted
* Perfusion weighted
What have Diffusion weighted and Perfusion weighted MRI sequences been tailored to identify?
Acutely ischemic stroke lesions that would not be visible otherwise
What doe DWI and PWI measure?
If parts of the brain are receiving enough blood
How can MRI be used to measure water in the brain?
It can be used to measure the movement (diffusion) of protons in water along fibre tracts. Movement is more in patients without brain tumors
Aside from tumors, what can MRI tracking movement of protons do?
It can be uses in research of illness like depression of autism
How can MRI be beneficial in mapping tumors?
In mapping proton diffusion we can superimpose it with the tumor and see which fibers are passing through and this can help with tumor resection
What are the advantages to Magnetic Resonance Spectroscopy (MRS)?
Provides quantification of specific metabolites or neurotransmitters in a specific region of interest without having to go inside the brain
What do MRI, MRS, and CT lack?
The don’t show the vascular aspect of the brain
What is an angiogram?
Using a radiopaque substance, or dye, to make the blood vessels visible under X-ray
What are the advantages of Angiograms?
There is very precise mapping of the blood vessels
What are the disadvantages of angiograms?
Requires a catheter to put into the blood vessels and injection of dye which can lead to vessel eruption or allergic reaction
What are the downside to some imaging techniques?
Sometimes a problem doesn’t affect the structure of the brain but instead the function of the brain cells
What does an EEG record?
The difference in electrical potentials generated by the brain
What are the advantages to the EEG?
- High temporal resolution
- Useful for monitoring state of arousal
- Cheap and available
What are the disadvantages to EEG?
- Poor spatial resolution
* Restricted to mainly cortical activity
What is the Alpha frequency range?
8-12 Hz
What occurs in Alpha?
Resting, awake, eyes closed
What is the Beta frequency range?
12 - 30 Hz
What occurs in Beta?
Aroused and awake
What is the Gamma frequency range?
30 - 100 Hz
What occurs in Gamma?
Perception/Binding brain activity
What is the Delta frequency range?
1 - 4 Hz
What occurs is Delta waves?
Deep sleep
What is the Theta range?
6 - 8 Hz
What occurs during Theta?
Exploration/memory and learning
What methods can be used when a finer location of epileptic activity than EEG is required?
- Grids to map finer location
* Depth electrodes to look at deeper neurons
What occurs in a Grid EEG?
Grids are put directly onto the brain for precise mapping
What occurs in a depth electrode EEG?
Depth electrodes are implanted into the brain for deeper structure recording
What neurons does Electromyogram (EMG) assess?
LMNs
What occurs in EMG?
A patient muscle activity is recorded either at the surface or using a needle inserted within the muscle
What are the advantages of EMG?
- Measure precisely activity in the muscle
- Can detect when the muscle in not getting enough nerve input
- Can help define the type of muscle disease
What are the disadvantages to EMG?
Can be painful with insertion of needle inside the muscle depending on location
What occurs in a Nerve Conduction Study (NCS)?
The patient nerve activity is recorded by stimulating the nerve and recording the time for its connected muscle to be activated
What are the advantages to NCS?
- Can precisely measure the nerve activity
* Can narrow down type of nerve disease by pattern of injury
What are the disadvantages of NCS?
Can be painful with the stimulation of the nerve
What is a clinical method for both UMN and LMN?
Genetics
What are the advantages to Comparative Genomic Hybridization?
Allows to map changes in copy number for the entire genome so do not need to know which gene could be affected in the patients
What are the disadvantages to CGH?
Is not table to tell if a patient has a single base pair change
What kinds of defects won’t be seen in CGH?
Defects in single base pairs
What kinds of defects won’t be seen in Karyotypes?
Defects in genes because of compaction
How big are the fragments of DNA in next generation sequencing?
Sequences are shorter
What are the advantages to next generation sequencing?
Multiple sequences at the time allow for faster and cheaper sequencing of exons or entire genome
What are the disadvantages to NGS?
- It is more error prone than one gene at a time traditional sequencing methods
- Needs a reference genome
Why might defects in genes not be seen in CGH?
Because they affect a single base pair in introns
Which neurons can a Lumbar Puncture measure?
UMN and LMN
What does a Lumbar puncture look at?
The level of RBCs, WBCs, glucose, and protein in cerebrospinal fluid
What is a Lumbar puncture very useful to assess?
Blood and infections in the CSF (aneurysm bleed, meningitis)
What are Lumbar Punctures used more for now?
Detecting auto-antibodies (ex. anti NMDA and others)
What are the advantages to Lumbar Punctures?
- Able to retrieve CSF which could help identify chemical, metabolic or immune differences
- Less invasive than getting brain tissue
What are the disadvantages of Lumbar Puntures?
- Requires the patient to be collaborative
* Risk of pain and infection
What are MRI based imaging methods based on?
The detection of changes in tissue and radiofrequency
What are Nuclear medicine based methods based on?
Injection of radioactive dye
What does a functional MRI (fMRI) measure?
The levels of oxyhemoglobin and deoxyhemoglobin in the brain and how they are modified by neuronal activity.
What are the advantages to fMRI?
They can show localization of brain activity at rest or when performing a task
What are the disadvantages of fMRI?
Requires a collaborative patient
What occurs in a Positron Emission Tomography (PET) scan?
Radioactive compounds that emit positrons are injected and the positrons collide with electrons and produce photons (gamma rays)
What are the advantages to PET scans?
- Measures precisely localization of brain activity
* Used to map cancer cells because they have high uptake
What are the disadvantages to PET scans?
Requires injection of radioactive tracer
What is the difference between SPECT and PET?
They are similar except gamma ray emitting radioactive material is injected instead of positron like in PET. And SPECT is not as precise as PET
What is reduced in patients with Parkinson’s disease?
[18F]dopa uptake in the putamen
What are the advantages and disadvantages to Magneto-encephalogram?
+Fast temporal resolution
-Very expensive, limited spatial resolution
What is Transcranial magnetic stimulation?
Using a coil to form a magnetic field which can then depolarize or inhibit the brain cells underlying it
What are the advantages to TMS?
•Can be used to understand localization of brain network without direct electrical stimulation
What are the disadvantages to TMS?
- Requires cooperation from patients
* Risk of inducing seizure
What two things is Single Pulse TMS used for?
- Mapping changes in cortical excitability during behaviour
* Mapping changes in cortical motor maps after stroke and during rehab
What is Repetitive pulse TMS used for?
- Inhibiting activity of specific cortical regions
- Enhancing functional recovery after stroke
- Reduction of chronic pain
- Treatment of depression, schizophrenia, addiction, anxiety
What does DBS consist of?
Insertion of depth electrodes into a specific area that is then stimulated either by a stimulator or by the patient
What diseases is DBS now used in?
Parkinsons, dystonia, severe depression, epilepsy
What are the advantages to DBS?
Can be very effective in some disorders and limit the need for meds
What are the disadvantages to DBS?
Risk of infection and invasive
