Lecture 25: Emotion and Flashcards
The limbic system
- The limbic system allows us to process emotions.
- It is generally thought that amygdala processes the emotional significance of external stimuli.
- The main function of the amygdala is to endow sensory stimuli with an appropriate emotional label (Aggleton, 2000; LeDoux, 2000).
- it is not only about + and - values, it is about establishing connection between the stimulus and the emotion that is associated with this stimulus.
- When there is a lesion to the amygdala it makes it hard to establish this connection or recognize an emotion driven by the information that is given.
- It is like the amygdala is labeling everything we are seing. (lOFC is about associating a value with a stumulus too).
- Weiskrantz (1956): “the effect of amygdalectomy … is to make it difficult for stimuli, whether positive or negative, to become established or to be recognized as such.”
Research question - is it only a lesion to the amygdala that will affect fear conditioning?
• Obvious role for the amygdala in fear conditioning, but rodent studies suggest the prelimbic (PL) part of the mPFC also plays a role in conditioned fear expression.
➢Microstimulation of PL increases conditioned freezing and inactivation of PL reduces it
• PL in rodents potentially homologous to dorsal anterior cingulate cortex (dACC) in humans. The PL in rodents is the equivalent to the dACC in humans.
• Studies show activation of the dACC during acquisition of fear conditioning but the role of the dACC in the expression of conditioned fear responses has not been well explored.
Goals of the first study
What is the role of the dACC in emotional conditioning, notably in conditioned fear? To test this we can record the brain and also record physiological responses. We can record the skin conductance response.
If we want to look at the role of the dACC in fear conditioning (and use MRI), we can:
- measure cortical thickness which is associated with the volume of grey matter in one region. Usually the volume within one region is correlated with the facility in processing information (more neurons to process info and have higher degree of cognitive processing. Usually, with greater grey matter = better responses.
We can also look at the functional activity, how neurons are reacting —> look at hemodynamic responses of the brain with fMRI. This looks at how much oxygen a neuron needs to have its response. More oxygen needed = neuron is responding to stimulate.
Are the measures that we are recording from the brain associated with the physiological response. Is it correlated?vIs one driving the other?
Materials and Methods
CS+ = paired with a shock
CS- = not paired with anything
We want to look at the activity for both conditions.
More about materials and methods
Structural MRI: automated measures of cortical thickness correlated with SCR especially with the trials to the CS+ that was averaged across trials
fMRI: first examined main effect of CS+ versus CS- (i.e. subtracted BOLD signal during CS- from CS+ trials) to see what areas of the brain respond to CS+
- Subtract the activity from one condition from the other to obtain the specific response associated with fear conditioning (see specific brain regions associated with CS+.
Next, to examine relationship of dACC and fear expression, examined how BOLD signal in dACC correlated with differential SCR (CS+ minus CS-)
Where in the brain is there the biggest correlation between the CS+ and CS- and the SCR.
Results: dACC thickness and SCR
• All subjects showed significant increases in SCR for the CS+ relative to the CS-, indicating successful differential conditioning
• Observed a significant positive correlation between thickness in the dACC region and SCR to the CS+
• In the BOLD signal analyses, observed a significant main effect of stimulus type across conditioning trials (CS+ versus CS-). Furthermore, dACC activation was significantly higher in response to the CS+ relative to the CS-. Greater grey matter but also greater functional activity in this region. BOLD signal is correlated with physiological response.
• Voxel-wise correlational analysis revealed a significant correlation between differential SCR and dACC activation. We take all the voxels where we see this increase for CS+ compared to CS-.
Conclusion
- (1) Found that dACC thickness was positively correlated with conditioned fear responses to the CS+, as indexed by SCR.
- (2) dACC functional activation increased to the CS+ relative to the CS- during fear conditioning, and dACC activity was positively correlated with differential SCR
- Further studies need to be conducted to determine the precise roll of dACC in fear expression.
- The location of the dACC region found to be correlated with fear expression approximates the target of anterior cingulotomy, an ablative neurosurgical treatment for patients with treatment-refractory mood and anxiety disorders. It can decrease anxiety –> leads to less reacting to negative situations.
- The dACC could be a potential target for future anti-anxiety therapies.
Stimulus value associations
from experiment: reinforcer-devaluation task
Amygdala:
* Formation of stimulus-value associations between discrete stimuli and their reward value
* In the reinforcer-devaluation task they will test updating stimulus – value associations. Updating stimulus is that we need to change the association between our stimulus and value.
Methods and Results of the reinforcer-devaluation task
- Amygdala not necessary for simple reward
feedback itself (e.g., in a typical visual
discrimination task) but rather formation of
stimulus-value associations between discrete
stimuli and their intrinsic reward. - For example, forming an association between a
visual appearance of a new food item with its
incentive value (how it tastes). - Reciprocal connections with OFC for updating valueof stimulus-reward associations
Method and Results for the reinforcer-devaluation task
Training:
* Learn to associate the pyramid with cherries and the cube with peanuts
Bilateral damage to the amygdala
Tests:
* Fed to satiety on their preference (cherries or peanuts)
* Animals with amygdala lesions select the object associated with their preference because the object value was not updated
Remember – strong connections with OFC – likely
where values are stored
Amygdala dependent
reward
processing
Amygdala:
* Linking objects with current stimulus value
* Updating stimulus – value associations
Amygdala is important in establishing the
value of particular stimuli
* Guides goal-directed behaviour and
decision-making
amydgdala is dependent on the reward processor.
What about Fear Extinction?
- Presenting the CS multiple times without the US leads to attenuated fear response
- Differentiate the training session from the testing (recall) sessions in fear extinction studies.
A possible hypothesis is plasticity - 1) it can reffer to the fact that we removed the fear condition or 2) maybe we created new conections.
Dual circuits for
regulating fear
response
- Basal nucleus (or basolateral nucleus) contains neurons that form part of fear response circuit AND other neurons that form part of fear extinction circuit
- These circuits involve the mPFC (either IL or PL) and determine the animal’s response (freezing or extinction) when CS is applied
In rodent brain, on the right we have the amygdala (the 4 structures). On the left we have the rodent equivalent of the vmPFC (IL) and the dACC equivalent (PrL). We will look at connections between these regions and the amygdala.
Red = neurons in the basolateral nucleus that react to fear conditioning.
one neuron (CS) responds to sound and the other neuron (US) responds to a shock by freezing. If every time that the sound is played, animal receives a shock then both of the neurons respond each time (AP together all the time). At one point, the two neurons will want to be efficient and so will change to create a path together (they will connect together) -> due to plasticity/LTP.
If we only present the sound and not the shock, it will still get the freezing because the 2 pathways are connected.
New connections are formed after fear extinction (seen in green). Fear extinction is the inhibition of the circuitry of fear conditioning, fear response. Fear extinction is associated with the vmPFC (IL), the basolateral amygdala and the medial central nucleus of the amygdala.
What did Milad and Quirk demonstrate oin 2012?
- Demonstrations of spontaneous recovery and fear renewal (e.g., due to change in context or over time) led researchers to realize that fear extinction is not due to the erasing of previously established fear associations (CS and US) but rather the strengthening of other synapses that form part of an inhibitory circuit
- It is, essentially, the learning of a new association: CS and No-US
Neural circuitry of auditory fear conditioning
- The amygdala became the centerpiece of the fear-conditioning circuit when it was shown that discrete lesions of the amygdala could block the acquisition and expression of conditioned fear responses (lesion to amygdala will block fear condition).
- Also that the lateral amygdala receives direct input from sensory areas
- With time, we were able to piece together the circuit of fear
conditioning
Amygdala receives inputs from the sensory and auditory which with go to the lateral part of the amygdala. There will be outputs/ responses from other nuclei from the amygdala.
Lateral amygdala RECEIVES inputs.
What are the inhibatory parts of the amygdala.
- Also began to learn about the inhibitory parts of the amygdala such as the (GABA)ergic intercalated cells, lateral division of the Central Nucleus, and inhibitory cells within the Basolateral Nucleus.
- Started to learn about the connections of the vmPFC to the amygdala
Rodent Infralimbic
PFC (IL)
- Quirk et al. (2000) made lesions of the vmPFC, focusing on the infralimbic (IL) subregion, and found that IL lesions did not impair the ability of rats to extinguish conditioned freezing responses within an extinction session (this lesion did not impair extinction), but rather, the rats were unable to retrieve their extinction memory at the start of the testing session (e.g., the next day)–> the extinction was no longer available, they could not recall it.
- This indicated that prefrontal circuits are not necessary for the initial learning of extinction but rather for the recall of the
extinction memory
Note: other studies have suggested area IL involved in
Milad and Quirk 2012 the learning phase as well as retrieval phase….
What happens in the circuitry of the Rodent Infralimbic PFC (IL)
- The Infralimbic region (IL) is important for retrieving extinction memory and can activate excitatory extinction neurons (green symbols) in the basal amygdala (BA).
- Extinction neurons activate highly specialised inhibitory interneurons, the so-called intercalated cells (ITCs), and/or inhibitory OFF-neurons in the central lateral amygdala (CeL). This will inhibith the fear reaction.
- Both types of neurons project to the important output station of fear circuits, the central medial amygdala (CeM), contributing to the inhibition of fear symptoms.
This is the basis for the CS-noUS memory trace (long-term)
Note: the same methods of LTP occur but at different synapses than the
fear response circuit!
vmPFC in humans
- Initial imaging studies focused mostly on within-session extinction learning and found increased amygdala and orbitofrontal cortex activation during extinction training.
- However, rodent data distinguishing recall of extinction from its initial learning called for a multiday conditioning/extinction paradigm in humans.
- Two-day fMRI protocols examiningextinction recall demonstrated activity in the vmPFC (Phellps et al. 2004)
