Lecture 9: Neurotransmitters in consciousness

Question 1

In what two ways can we talk about consciousness according to this lecturer?

Answer 1

We can talk about in terms of experience and content. This can be manipulated on various levels like subliminal, preconscious or conscious, by masking, crowding, attentional manipulations and binocular rivalry.
We can also talk about consciousness as a state/level (also called wakefulness or vigilance), on various levels as coma, vegetative state, sleep or wakefulness.

Question 2

Neurons go from early visual areas to higher visual areas. The RF’s become larger, and the informations processed become more complex. There is for example a Jennifer Anniston cell that fires when subjects look at pictures of her. But is it when that cell fires that subjects become aware of Jennifer?

Answer 2

No, in a study with anaesthetised monkeys they were shown pictures of faces and houses and although monkeys were clearly not aware of that stimuli (they’re anaesthetised), the FFA and the house regions were activated. Also human subjects in coma, under narcoses or sleep show activation in auditory cortex when they’re talked to. This is also the case for content manipulation by masking etc. Therefore activation in high level brain areas does not equal consciousness

Question 3

Even unconscious brain shows neural activity in higher brain areas so it isn’t sufficient for consciousness to arise. So which neural activity is necessary according to the lecturer?

Answer 3

Recurrent processing followed by feedforward seems to be crucial. In the previous studies feedforward sweep was present but the recurrent processing was disturbed. Recurrent processing consists both excitatory long-range feedback connections as well as lateral inhibitory connections to integrate and select information.

=> Consciousness requires integration of information via Recurrent Processing.

Question 4

What is the difference between agonistic and antagonistic drugs?

Answer 4

Agonistic drug mimics the neurotransmitter and enhances the transmission. They occupy the receptors and activate them.

Antagonistic drugs block neurotransmitters by occupying the receptors and blocking them.

Question 5

What are the two most widely drugs used for anaesthesia? What roles do they play?

Answer 5

GABA and NMDA are the widely used drugs for anaesthesia.

> GABA is the main inhibitory transmitter.
NMDA-receptor is a receptor which glutamate is sensitive to and glutamate is the main excitatory neurotransmitter.

Question 6

Unrelated, from book. What was found to cause ‘out of body experiences’ through research?

Answer 6

After investigating many neurological and surgery patients, Blanke discovered that a cortical region in the right temporoparietal junction, when impaired or electrically perturbed, repeatedly caused a sensation of out-of-body transportation. This region is situated in a high level area where multiple signals converge: those arising from vision; from the somatosensory and kinesthetic systems (our brain’s map of bodily touch, muscular, and action signals); and from the vestibular system (the biological inertial platform, located in our inner ear, which monitors our head movements). By piecing together these various clues, the brain generates an integrated representation of the body’s location relative to its environment. However, this process can go awry if the signals disagree or become ambiguous as a result of brain damage. The out-of-body state is, by and large, an exacerbated form of the dizziness that we all experience when our vision disagrees with our vestibular system, as on a rocking boat.

Question 7

What neurotransmitters and receptors are involved in excitation?

Answer 7

Neurotransmitter- Glutamate

Receptors- NMDA & AMPA

Question 8

Define inhibition

Answer 8

The capacity of an excited neuron to reduce the activity of its neighbours.

Question 9

What neurotransmitters and receptors are associated with inhibition?

Answer 9

Neurotransmitters: GABA
Receptors: GABA

Question 10

What must we do in order to reduce consciousness?

Answer 10

We decrease excitation with antagonists. Increase inhibition with agonists

Question 11

What are the mechanisms by which this reduces consciousness?

Answer 11

Recurrent Processing consists both NMDA (Glutamate) excitatory long-range feedback connections as well as lateral GABA inhibitory connections to integrate and select information. Feedforward connections are made by AMPA, feedback connections are with NMDA and finally NMDA &GABA helps the global ignition. As consciousness requires integration of information and selection for access, having these two in research is very useful.

Integration of information: Recurrent loops via AMPA & NMDA.

Question 12

Why is GABA necessary for consciousness?

Answer 12

Consciousness also requires selection for access. You cannot be aware of every object in a busy image simultaneously.

Selection for access -> Determines what consciousness is not, so inhibition

Question 13

Where in the neurotransmission process do these drugs act?

Answer 13

Post-synapse

Question 14

So what is pharmacology in consciousness research?

Answer 14

So pharmacology in consciousness research is increasing inhibition (GABA-agonist) or decreasing excitation (AMPA/ NMDA-antagonist) to reduce neural activation.

Question 15

What drug and measurement was used in Anouke’s research involving bistable perception?

Answer 15

GABA and Magnetic resonance spectroscopy

Question 16

Why was GABA used in Anouke’s research involving bistable perception?

Answer 16

Some examples of bistable perception are Structure From Motion and Binocular Rivalry. In these cases the content of the conscious perception spontaneously fluctuates in face of constant sensory input. This happens with inhibition.

Question 17

Describe the procedure of Anouke’s research involving bistable perception

Answer 17

Participants are wearing glasses with one eye blue glass and the other red glass. They’re looking at the screen where they either see a green image or a red image (image is the same but their percept switches). It was seen that as inhibition decreases, the switch gets faster and more often. And as inhibition increases the switch gets slower and less. They then measure the GABA concentration as measure of inhibition to link the perceptual dynamics of bistability. The prediction was: more GABA in visual cortex would lead to slower perceptual dynamics. They used a Magnetic Resonance Spectroscopy (MRS) which is a quantitative method to measure the concentration of molecules in a specific region of the brain.

Each individual’s concentration of GABA was measured and correlated with a behavioural or neural measure. Visual Cortex voxel was measured but the Right Dorsolateral Prefrontal Cortex voxel was also measured as a control.

Question 18

Describe the results of Anouke’s research involving bistable perception

Answer 18

For binocular rivalry, the higher the mean percept duration, the higher was the GABA concentration, so a positive correlation between them. Same was the case for Motion Induced Blindness and Structure From Motion tasks.

=> Therefore, higher GABA in visual cortex leads to slower perceptual dynamics.

Then they interfered and played with GABA by giving a receptor agonist, Lorazepam. Participants were given either a placebo pill or Lorazepam. And it was predicted that there would be slower perceptual dynamics with lorazepam. This was indeed the case in the results. For Motion induced blindness, the mean percept duration increased and the switch rate decreased (for Lorazepam). And Same was the case for SFM.

Question 19

What drug and measurement did Anouke use for her study on objects recognition?

Answer 19

NDMA, Ketamine; fMRI

Question 20

What did this ket study intend to investigate?

Answer 20

This study investigated the role of feedback activity in shaping neural representations in early visual cortex during object recognition.

Question 21

What stimuli was used in this study? Why?

Answer 21

They used a Mooney image (the one with the Dalmatian dog) as it gives the opportunity to study the effect of object recognition by comparing the effect before and after recognition.

Question 22

Describe the fMRI technique used in this ket study

Answer 22

They used the multi voxel pattern analysis to decode information. We look at the pattern of activity in our region of interest. For example if there is a 10 by 10 voxel where white is very active but black isn’t really, we can look at the pattern of activation of the voxels. Then we can compare to see if the voxels act similarly. So we can distinguish between stimulus types within a region of interest.

We give an order to the voxels (1 to 10 in a 10 by 10 voxel region), then we put their strength of activation in order according to the order of voxels. These orders of voxel activations give us patterns. Then we can compare them either within category or between categories (correlation) to see how similar their behaviours are. Within category comparisons appear to elicit similar patterns and high correlations, while between categories the opposite is found.

Question 23

How was this technique applied in this study?

Answer 23

In this study they carried out this analysis in the visual cortex and the object-selective cortex. They compared the pattern of activity:

> When they first saw the mooney vs photo
When they second see the mooney vs photo
First mooney vs second mooney (high correlation)

Question 24

What was the result of this study before the application of ketamine? (previous study)

Answer 24

Correlations between the mooney image before they saw the greyscale version were similar to between category correlations (low correlations). The correlations of when they seen the mooney image after seeing the greyscale image were similar to within category correlations (highly correlated). Correlations between the first time seeing the mooney image and the second time were also highly correlated. These results were found in both the visual cortex and object-selective cortex.

Question 25

What is significant about the previous researchers finding these results in these brain areas?

Answer 25

Very interesting that they found it in the early visual cortex. It was suggested that this must be the result of feedback information from higher up processes.

Question 26

Describe the procedure of Anouke’s study

Answer 26

In this specific study, their design was placebo-controlled, double-blind within-subjects. They had two sessions that are counter-balanced and separate sessions for retinotopic mappers.

Two conditions, ketamine injection and placebo injection. First they carried out the first mooney identification task and then the drug was injected.

It was a categorisation task in which the participants were shown the mooney image (mooney 1), the greyscale (greyscale), both paired (paired) and then the mooney image again (mooney 2). Each of these phases had 3 runs with 48 trials per run and 4 presentations/ stimulus except for the paired phase which had no scanning, 24 trials and 2 presentations paired. A trial consisted of fixation (2-32 sec), target being displayed (180ms) and response (1500ms). Subjects had to report whether it was an animal or not.

Participants then rested before carrying out some behavioural tasks and drugb administration was ended. Participants then carried out the second identification task.

Question 27

What were the behavioural results of the study?

Answer 27

Behavioural data showed that after the injection the ketamine condition felt more sedated. Also, for the Mooney Identification Task, people were better at identifying it at the end than before. Also categorisation improved (animal or not animal) and the RT decreased.

Question 28

What predictions did the researchers have?

Answer 28

Researchers predicted that the recognition would increase the dissimilarity (‘Mooney1 < Greyscale’ ‘Mooney1 < Mooney 1’) and Ketamine reduces top-down activity meaning decreased recognition effect specifically in early visual areas. They created matrices to analyse this.

Question 29

What were the results of the study?

Answer 29

It was found in the pFs that:
In the placebo condition, all mooney1 images were very similar to each other, just some b&w dots. In Greyscale, they showed more dissimilarity. In Mooney2, the images also became more dissimilar to each other. And when Greyscale and Mooney2 were compared, they were more similar to each other.

It was found in the V1 that:
Placebo condition the results were the same a above. But when it comes to the Mooney2 results of Ketamine, contrary to the other results, participants showed no increase in similarity. So Ketamine abolished the effect, Mooney1 and Mooney2 did not differ. The Mooney2 under ketamine were different than the ones in placebo.
This abolishment is only found in V1 and V2.

Then they also used the classifiers to analyse the results after training the programme. In placebo, the programme ended up categorising the Mooney2s with Greyscale 75% of the time indicating that they are very similar. Ketamine reduced this effect in V1/V2 ( classification was at chance level).
So Ketamine reduces the recognition effect, specifically in V1.