Lecture 6: Biomarkers Flashcards
Explanation of biomarker
- A characteristic that is objectively measured.
- Evaluated as an indicator of normal biological processes
- …of pathogenic processes
- …or of pharmacologic responses to a therapeutic intervention.
Why do we have an urgent need for biomarkers?
- ~35% of EU health-care costs relate to brain disorders.
- 127 mill EU citizens affected.
- Cognitive disorders not recognized as “biological” (like a broken leg).
- Diagnosis is inaccurate.
- Treatment options are insufficient.
- Lack knowledge to develop rational treatment strategies!
- Large individual variation in how patients respond to a given drug => patient stratification or “personalized medicine” is on the rise.
What do oscillations correlate with?
Cognitive processing in normal subjects. So this is why oscillations may index cognitive disorders and can be used as a substrate for biomarkers.
What two biomarkers are there already for Alzheimer’s disease?
- Biochemical biomarker, amyloid deposition.
- Non-invasive image marker, cortical volume
(Not sensitive or specific enough)
What are advantages of biomarkers from functional brain imaging data?
Possibly closer to the impaired function, may reflect symptomatic relief despite progression of pathology (e.g. atrophy or elevated amyloid)
What are disadvantages of biomarkers from functional brain imaging data?
- Inherently dynamic (variability)
- Sensitive to state changes (alertness, motivation, …)
- Require a task
What is the task dilemma?
Cognitive paradigms demanding for patients. So you need a simple task (easier for patients and also clinicians), like the ECR test.
What happens in the brain when you present different items and increase the retention interval (so that they have more time to process the items in the working memory)?
That there will be an elevated activity of alpha during the retention interval. This oscillatory activity increases when the retention interval increases. So this says that retaining oscillatory activity in the temporal structure is important for memory.
So based on the hypothesis that temporal structure of oscillations is important for working memory (1) and Alzheimer’s patients cannot sustain oscillatory activity (2).
An experiment with a memory task was performed, where all oscillatory bursts are measured and turned into a cumulative probability distribution. They looked at the 95th percentile and saw that 95% of the oscillatory bursts were shorter than 400 ms. This data was then converted to scalp topographies. What became clear when they compared Alzheimer patients with a control group based on these scalp topographies?
That alpha oscillations are much more and longer present in the parietal region of the control group compared to Alzheimer patients (this makes sense given the fact that the parietal region is important for memory). And theta oscillations were much more and longer present in the frontal region of Alzheimer patients compared to the control group.
For this same experiment, we could also look at long-range temporal correlations.
- What do you see if you look at the DFA of alpha oscillations of Alzheimer patients and control?
- What do you see if you look at the amplitude alpha oscillations of Alzheimer patients and control?
- Alpha oscillations have much more temporal structure (higher DFA and LRTC) in the parietal region compared to Alzheimer patients.
- The amplitude doesn’t differ much.
Can you use this diagnostically? Why (not)?
No, because there’s no spreading and you need to take individual variation into account.
So, what is another way to diagnose if we can’t use this for diagnosis?
To compare the EEG data of the individual with its own EEG data, but then some time apart. You can then see if there were any changes that occured during that time. Or by combining two or more independent biomarkers (e.g. the alpha biomarkers discussed previously)
We’ve discussed that theta waves might be a biomarker for Alzheimer’s. What reason is there for it to not be a biomarker?
Theta waves were more active and longer present in the frontal region of Alzheimer patients. But they saw that sleepy student displayed the same kind of activity, so it just might be that Alzheimer patients are more sleepy in general. (Therefore, the ARSQ is important in assessing biomarkers).
