Lecture 13: Neuroscience in the Clinic

Question 1

What theory was the study ran by (1) Bekinschtein and (2) Casali inspired by? Also give the type of paradigm used

Answer 1

(1) Bekinshtein was inspired by GNWS theory and used a Local-Global paradigm as an active paradigm
(2) Casali was inspired by information integration theory and used PCI as a passive paradigm

Question 2

Describe the procedure of the study ran by Bekinschtein

Answer 2

Subjects are listening to tones, and they always listen to 5 tones in a row. In the local standard condition, all the tones are identical. In the local deviant condition, the last tone is different than the one before (xxxxY). This mismatching sound creates a mismatching reaction and a P3 reaction in the EEG. In this experiment they created conditions that helps isolating this MMN activity as well as the P3 response, and tested the relationship with awareness of regularities.

xxxxx runs: Habituation phase, the subjects are presented with the same stimulus over and over again. Then in the test phase, they add 20% of rare trials (so global deviants; xxxxy). This way, this deviant is not just a local deviant but also a global one, as the other 80% of the tones are identical as the 4/5 in the sequence.

xxxxY runs: This is the same process, but the other way around. This time, there is not a local deviant but the set of 5 identical tones is a global deviant (au total).

Now we can create a local effect by contrasting between local deviants and local standards. Also a global effect by contrasting between rare trials and frequent trials.

Question 3

What is the logic behind these two conditions?

Answer 3

To detect a global deviant one has to integrate information across longer periods of time (maintenance of information as a signature/function of consciousness) SO it requires recurrent interactions and thus consciousness.

Question 4

What is the aim of this paradigm in regards to EEG?

Answer 4

This way we can isolate MMN responses that are related to the local effect and P3 responses which are related to the global effect.

Question 5

Describe the EEG results of this active paradigm study

Answer 5

There is a very clear frontal negativity very early on, this is the MMN. First frontal activity is the reflection of the MMN, the ERP comes at about 150ms. It’s a negative component peaks at frontal electrodes around 150ms. (On the graph standard is in green and the deviant is in red).

For the global effect, we see the P3b reaction, which is a strong positive activity from 260ms onwards. Seen in Parietal electrodes.

Question 6

This experiment was done on subjects who were paying attention to the auditory stimulus. Then they did this again on subjects who were doing task irrelevant stuff and the sound was in the background. What were the results? What does this suggest?

Answer 6

It was seen that the P3b has disappeared but the MMN was still present. Suggests that P3b is really related to consciously accessing the information, whereas MMN is an automatic reaction.

Question 7

Describe the fMRI results of the active paradigm study

Answer 7

For the local effect which was reflected by the MMN in EEG, only local activity is seen in the auditory cortex.

For the global effect that was seen by the P3b in EEG, there is a fronto-parietal network activity involved.

Then the intracranial results showed the same data as EEG with MMN and P3b.

Question 8

How is this study (1) clinically relevant?

Answer 8

This again brings us to the point we have been making over and over again during the course, there is a fronto-parietal activity when participants show awareness and absence of activity when subjects are unconscious. The same paradigm was tried on patients with Minimally Conscious State and the Vegetive State.

Question 9

Describe the results of the active paradigm in patients with disorders of consciousness

Answer 9

Minimally Conscious State (4) and the Vegetive State (4): For local effect, we see that all patients except for VS4 show some kind of reaction to the deviant stimulus. For global effect, we don’t see any strong significant difference, and only 3 patients show some kind of reaction. Follow-up showed that these 3 MCS patients recovered to a fully conscious state. None of the vegetative state patients showed the global effect.

Question 10

What can be inferred from the results of the active paradigm study on DOC participants?

Answer 10

Local effect is almost always present, irrespective of the level of consciousness. On the other hand, the global effect is more predictive of the consciousness at that moment, as well as the recovery possibility in the future.

Question 11

Why is it important to test several times, especially in MCS patients?

Answer 11

As consciousness fluctuates, especially in MCS patients, it is important to test several times instead of just once.

Question 12

Give some pros and cons of this active paradigm

Answer 12

EEG is much cheaper and easier to carry around in the clinic (compared to fMRI)

Experiments are difficult to perform in the clinic, they require a lot of expertise.

Theoretically inspired by the global workspace idea. We check for information integration, as a function of consciousness, in the brain.

The task seems more sensitive, requires fewer residual cognitive functions, although it is still an issue.

Question 13

What is the mechanism being measured in the second passive paradigm?

Answer 13

Connectivity and durability of information processing

Question 14

How can they use this connectivity and durability as a measure while people are asleep (in non-rem sleep while there’s no dream) vs awake?

Answer 14

They stimulated the brain with TMS and measured with EEG what happens to that external stimulation. The brain processes the stimulation and the extent to which we see the pattern of information exchanged between the brain regions as well as how long this process lasts are indications of the level of consciousness.

The processing of the information was more durable and wide spread when people were awake compared to when they were asleep. Interpreted as the brain is more connected when people are awake and this allows the information to be spread.

Question 15

A breakdown of long-range cortical connectivity during sleep was done. What was observed?

Answer 15

A lack of spreading of activation during sleep (loss of consciousness) was seen.

Question 16

What was found when they carried out this measure on anaesthised patients?

Answer 16

Similar result to sleeping patients

Question 17

They studied whether PCI would be able to differentiate conscious vs unconscious. What is meant by PCI?

Answer 17

PCI (perturbational complexity index), PCI is a value between 0 to 1, representing the degree of complexity of information processing. (They reduce the whole complicated series of event that are produced by the TMS, into a single value, which reflects the presence of integration and differentiation over a specific time-window)

Question 18

How is the PCI relevant to disorders of consciousness?

Answer 18

They compute this value for all different types of situations, so all different levels of consciousness, using different types of interventions (like anaesthetics or sleep). When people are on a conscious state, the PCI is about 0.5-0.6. When people are not in a conscious state, PCI is around 0.2, maybe 0.3.

Question 19

Describe the differences in PCI for people at different levels of consciousness relative to a time scale

Answer 19

When we look at the time scale we see that the initial reaction triggered by the TMS show relatively similar complexity for all conditions, but at some point they start to differ (usually around 100ms). This resonates with the feedforward/feedback sweep, recurrent interactions. It is mainly the longer-lasting pattern that differentiates conscious vs unconscious.

Question 20

They then studied whether PCI can discriminate different levels of consciousness. Describe the results

Answer 20

As we move from behaviourally diagnosed unconscious states towards the conscious states, the PCI value also increases. We also see that the CRS-revised value increases, which is a measure to detect the level of consciousness

Dotted lines show whether they’re conscious or unconscious (for sure) and it can be seen that all patients of LIS are clearly above the red line. People in between have fluctuating consciousness or, if they are unconscious, we can estimate that they will become conscious.

Therefore, this measure (PCI) nicely reflects the behavioural measures we make.

Question 21

Describe the results of a paper which studied the recovery among patients of disorder of consciousness.

Answer 21

1st pulse was administered the day the patient began to emerge from coma produced localised patterns that faded quickly.

2nd pulse was several days later, and it showed patterns that were more widespread and longer-lasting.

3rd pulse was performed after the patients regained consciousness, and produced the most complex and longest lasting patterns.

When it was done on patients who have never recovered, no long-lasting, complex patterns were found. So it can be concluded that regaining consciousness is related to an increase in overall brain connectivity.

Question 22

What is an advantage of this approach and why?

Answer 22

=> Advantage of this approach is it being passive.
>It doesn’t depend on the integrity of sensory pathways or on the subject’s ability to comprehend or carry out instructions. (what behavioral measures do)
>It doesn’t require any residual cognitive functions of the patients that might be absent, whereas consciousness is still present. (what active paradigms do)

Question 23

What does Simon think the benchmark of a diagnosis is?

Answer 23

Simon thinks the benchmark of diagnosis is always or very often still the clinical diagnosis (Coma Scale Score). The neuroimaging techniques are additions. Because there is no golden standard to indicated the presence and absence of consciousness.

Question 24

What does Simon think the best approach is when two methods disagree? What is a disadvantage of this?

Answer 24

Simon thinks the best approach is a multimodal approach with behavioural, fMRI, EEG etc measures. Several measures combined over longer periods of time.

However it is very expensive and time consuming.