Emotion and the brain

Goals

• To discuss the amygdala
• To discuss the neural circuit of fear conditioning and extinction
• To discuss the history and theories of emotion.
• To discuss the limbic system and its role in emotion.
• To discuss the amygdala.

Topic slide

Elizabeth Phelps was formerly a professor in Yale Psychology who moved to NYU and is now at Harvard. Phelps has conducted many influential studies of emotion and the brain with a focus on studies of the human amygdala.

Joseph LeDoux (b. 1942) is a neuroscientist at NYU. Probably more than anymore, LeDoux brought the study of emotion into the mainstream of modern neuroscience with his work on the neurobiology of fear conditioning.

Reading

• Reading: PN6 Chapter 31

Amygdala

In the coronal view of a human brain specimen below, the amygdala is labeled with ‘a’ (see red arrow). It is located in the medial portion of the temporal lobe. A small oval shaped cluster of cells from the most anterior hippocampus can be seen below the amygdala. The parahippocampal gyrus (phig) and the fusiform gyrus (fs) of the temporal lobe can be seen below.

The amygdala is composed of several nuclei which are typically grouped into four major groups as numbered in the figure below. In this figure, the red lines indicate efferent connections from the nuclei of the amygdala and the green lines indicate afferent connections from other regions of the brain to the nuclei of the amygdala.

1. The (1) corticomedial group provides the main efferent pathway from the amygdala to the hypothalamus through a pathway called the stria terminalis.
   • The corticomedial group receives afferent input from the hypothalamus.
   • The corticomedial group also has reciprocal (i.e., both afferent and efferent) connections with ascending neuromodulatory systems involved in arousal.
2. The (2) cortical nucleus is the recipient of olfactory input to the amygdala.
   • The cortical nucleus sends its output to the corticomedial group.
3. The lateral nucleus (3) and the basal and accessory basal nuclei (4) of the amygdala are often grouped together as the basolateral nuclei.
   • The basolateral nuclei receive afferent input from the hippocampus, entorhinal cortex, and sensory cortices.
   • The basal and accessory basal nuclei receive input from the lateral nucleus and send output to the corticomedial group.
   • The basal and accessory basal nuclei also send output to structures that comprise the limbic and reward systems via the ventral amygdalofugal pathway.
   • The basolateral amygdala is involved in fear conditioning, as will be discussed later in this lecture.

Fear conditioning

Fear conditioning and extinction

Fear conditioning is just a variant of classical conditioning. In the classical conditioning field, the shock would be called the unconditioned stimulus (UCS) and the innocuous stimulus would be called the conditioned stimulus (CS). Normally, an animal would respond to the UCS with an unconditioned response (UCR), such as jumping in pain. After many pairings of the CS-UCS, the CS evokes a conditioned response (CR) prior to the appearance of the UCS. This CR might be a freezing response. The appearance of the CR in response to the CS is evidence of learning, i.e., the animal predicts the appearance of the UCS based upon the appearance of the CS.

I discussed the neural basis of fear conditioning (based primarily upon the work of LeDoux) using a diagram (below) that I modified from a review article by Maren (2011) that can be found here.

The key points are that the lateral n. of the amygdala receives sensory input about the conditioned stimulus (a tone, in my example) from the medial geniculate of the thalamus and the auditory cortex (AC). The corticomedial group (central nucleus) of the amygdala receive information about the unconditioned stimulus (the shock, in my example) from the PIN (posterior intralaminar nucleus of the thalamus). The output of the corticomedial group evokes the conditioned responses – such as freezing, changes in heart rate, initiation of the HPA axis and release of glucocorticoids, etc.

Extinction is a type of new learning, whereby the CS appears without the UCS. Over several CS appearances without the UCS, the CR diminishes. The diminishment of the CR is evidence that the animal has now learned that the CS does not predict the UCS.

I introduced the concept of extinction learning. Extinction is a form of learning, not ‘forgetting’. In extinction, one learns that a cue previously associated with a (usually aversive) outcome, no longer predicts the bad outcome.Ventromedial prefrontal cortex and the hippocampus play an important role in extinction learning. Lesions to the vmPFC abolishes extinction for a given conditioned fear. The hippocampus also provides context information about fear conditioning – for example, whether the animal received fear conditioning training in this particular training box, or the time of day of fear conditioning.

I showed that extinction learning in humans is correlated with the thickness of vmPFC cortex. The thicker the cortex, the better the extinction learning.

Reconsolidation

Many memory theorists believe that memories become labile and susceptible to modification whenever they are recalled. That is, when we reactivate a memory, it can be reconsolidated with new information. Thus, memories are constructive, and subject to manipulation.

Reconsolidation is often discussed in the context of fear conditioning, where an aversive stimulus (e.g., an electric shock, or an air puff to the eye) is preceded by an innocuous stimulus (e.g., a tone, or a colored light).After CS-UCS training, the presentation of a solitary CS (without UCS) is a cue for the CS-UCS memory. The memory is thought to be labile, and susceptible to reconsolidation. In experimental animals, giving a drug that inhibits protein synthesis (anisomycin) after a solitary reminder CS interferes with the reconsolidation of the old memory. Thus, the animals forget that the CS predicted a shock. When tested later with a CS, they show diminished CRs, indicative of poor memory for the CS-UCS pairing during the initial learning. Studies in animals show that the temporal window for reconsolidation is brief. If the solitary CS is given to reactivate an old memory, and the protein inhibitor is given 24 hours later, it has no effect on reconsolidation.

If in humans, you recall a memory with a solitary CS, and then immediately begin extinction training (while the memory is labile for reconsolidation), the human quickly learns the new information and extinguishes well. If you recall a memory with a solitary CS, and then wait until the temporal window for reconsolidation to be over before commencing an extinction trial, extinction is less effective.

Reconsolidation and pathological memories

We saw earlier in the semester that an NMDA antagonist can inhibit learning and memory in rats swimming in a Morris water maze. Can an NMDA agonist improve learning/memory? Can this help clinically in patients with traumatic memories?

Reconsolidation may provide a way. D-cycloserine is an antibiotic and NMDA agonist. It is being tested with virtual reality exposure therapy. If you recall a fearful memory (by exposing patient to a cue) in a safe environment (a form of extinction learning), perhaps providing a NMDA agonist will speed extinction learning.

This is a relatively new area of research, and the findings thus far must be viewed as preliminary, but also provocative.

• Acrophobia – helps patients unlearn fear of heights
  • SCR measures and fear ratings
• PTSD and exposure therapy
  • Although studies just underway, there may be support for the idea that VR exposure therapy plus NMDA agonists can alter traumatic memories.

Do you think this approach of manipulating memories has negative ethical implications?

Emotion

Category and Dimensional models

How we conceptualize emotions strongly influences how we explore their neural bases.

Paul Ekman

• Categorical theory of emotion – Ekman's research showed that people in very different cultures nevertheless interpreted six emotions (happy, sad, anger, fear, disgust, surprise) consistently, suggesting that some emotions are universal. This led some neuroscientists to see where in the brain these six emotions were generated.

Dimensional: Valence and intensity

• Valence models divide emotions into positive and negative.
• Intensity models express emotions along a scale that goes from neutral to intense.
• A popular ‘vector’ model combines valence and intensity

Emotion influences other brain processes/functions.

Memory

• Flashbulb memories are memories that accompany a very emotional event – such as where were you when the World Trade Center was attacked on 9/11?
• Studies show that flashbulb memories evoke strong emotions in the individual recalling the memory, and this is associated with amygdala activation.
• However, recent research has shown that while very emotionally vivid and while subjects are quite confident about them, they are subject to forgetting and distortion.

Attention

• Face in crowd effect: An angry face pops out of a background of happy faces. By "pops out" we mean that the detection time for an angry face amongst happy faces is not influenced by the number of happy faces. That is, visual search is parallel. However, a happy face does not pop out of a background of angry faces. This suggests that there is an advantage – perhaps related to evolution – that makes detecting negative emotions important.
• Dot probe task: If a task requires you to detect a dot a quickly as possible, you will be faster if the dot occurs at the same location as a previously presented task-irrelevant emotional face compared to a neutral face. This suggests that the emotional face summoned attention to its location, and you were faster when the dot was located where attention was already located.
• Eye tracking studies have demonstrated that we tend to scan emotional rather than neutral images.

Historical theories of emotion

I discussed in lecture various treatises on emotion prior to the modern era. Most interesting from our perspective was that of Darwin, who wrote a book on the commonalities of emotional expression in humans and animals and suggested that emotional expressions must have been preserved by evolution.

James-Lange theory:

• "We feel sad because we cry, angry because we strike, afraid because we tremble, and neither we cry, strike, nor tremble because we are sorry, angry, or fearful, as the case may be."
• The source of emotions are the behaviors/events that invoke bodily sensations, and we interpret them as emotions. In this scenario the emotions follow these bodily sensations. That is, the visceral sensations are the source of emotions.
• This suggests that there are different bodily states for different emotions.
• It also suggests that without visceral bodily sensations, there should be no emotions.

Cannon-Bard theory:

• Here emotions and the bodily states happen at the same time. We run because we are afraid. In the C-B theory, it is the thalamus that generates emotional states on the basis of sensory input.
• C-B noted that people can have the same bodily states – say increase heart rate and respiration – but it will associated with running from a bear in one state – fear – or running in a race in another state – not fear. This suggests there are not different bodily states for different emotions.

This website does a good job of distinguishing James-Lange from Cannon-Bard theories. The video is also good, but it stops playing at the mid-point unless you register for the site.

Schacter and Singer:

• In an experiment that would be unlikely to win approval with a human ethics committee, S&S gave participants a shot of epinephrine to evoke increases in heart rate and respiration. They then put the subjects into different situations. The subjects interpreted their bodily state as the emotion evoked by the experimental situation in which they were placed.
• This is similar to J-L, in that the subjects emotional state was an interpretation. It was similar to C-B in that the bodily state was an identical response to epinephrine – despite the different interpretations.

Somatic Marker hypothesis

Somatic marker hypothesis by Antonio Damasio and colleagues:

• "somatic states" are bodily states (akin to "emotional states")
• Primary inducers are innate or learned stimuli that cause pleasure or pain
  • Triggered by the amygdala – somatic loop
• Secondary inducers are thoughts and memories associated with somatic states (e.g., "the feeling of winning the prize", "the feeling of breaking up with your partner")
  • Triggered by the vmPFC – "as if" loop

Emotions are reinstated with the memory, and guide decisions through experience of their consequences.

Somatic marker hypothesis using Iowa Gambling task

This was tested by Damasio and his colleagues in patients with vmPFC lesions:

• In this task, a subject chooses a card from one of two piles of cards. One pile is ‘high risk’ with some high gain cards but also many high loss cards. The other pile is ‘low risk’ and subjects steadily make money with this deck.
• Normal volunteers shown skin conductance responses (SCR) (indicative of arousal) prior to taking a card from the risky deck.
• Patients with vmPFC lesions do NOT show a skin conductance response before taking from the risky deck. They do, however, evince an SCR when they also take more frequently from the risky deck, and thus lose money.
• Sometimes the subjects will state that they are being foolish ("say the right thing") but nevertheless still take from the risky deck ("do the wrong thing").
• The implication from the bad choices and the lack of advance SCR is that the individuals with vmPFC lesions are not experiencing ‘somatic markers’ associated with their decision to choose from the risky deck. And thus they make bad decisions and lose money.
• In this formulation – Spock from Star Trek would not be a good decision-maker, as he does not have emotions and thus can’t have somatic markers.
• Note also that the lack of somatic markers might make a subject with vmPFC very utilitarian with respect to moral decisions –s we will consider that later this semester.

Brain-viscera communication and emotion

One of the differences between the J-L and C-B is the role of the bodily sensations in communicating information related to emotional states to the brain.

I discussed some conflicting evidence that high cervical lesions eliminate some sensations from the body in humans dampens emotional experiences. Many studies suggest that this is true, however, there are also data that suggest it is not true.

I am not certain that the spinal cord lesion studies are decisive on this point, because sensations from the gut (viscera) are communicated to the brain from the vagus nerve (Xth cranial nerve) which does not run through the spinal cord. Thus, even with a severed spinal cord, one would still receive visceral bodily sensations that are often associated with emotional states. Recent studies using TMS over the vagus nerve have shown increased emotional perception compared to sham TMS.

A good review of brain-viscera interaction can be found in a recent review by Mayer 2014. I have copied below a section from this review that discusses the relationship of the viscera to emotion theory. This nice summary recapitulates many of the points I have discussed above.

The first comprehensive scientific theory of brain–viscera interactions was formulated in the 1880s by William James and Carl Lange and was based on the central concept that stimuli that induce emotions such as fear, anger or love initially induce changes in visceral function through autonomic nervous system output, and that the afferent feedback of these peripheral changes to the brain is essential in the generation of specific emotional feelings. According to this theory, we feel anxious because we perceive our heart beating faster, because we become aware of our respiration becoming more frequent and shallower, or because we feel ‘butterflies’ in our stomach.

In the late 1920s, Walter Cannon challenged the James–Lange theory, postulating that emotional feelings are generated directly by subcortical brain regions rather than from the feedback of situational bodily changes. He proposed that such bodily changes that are associated with emotional states are simply by-products of these brain changes, and that the visceral responses are too slow to play any part in the subjective experience of emotional feelings.

Modern theories of emotion and consciousness that were proposed in the form of the ‘somatic marker’ hypothesis by Antonio Damasio, and the ‘homeostatic emotion’ hypothesis by A. D. Craig have re-emphasized the importance of interoceptive feedback in emotional states and cognitive processes, and have largely overcome the long lasting controversy about the directionality of brain–viscera interactions in the generation of emotions. For example, Damasio eloquently proposed that somatic markers (for example, memories of body states associated with previous feeling states) arise from positive or negative emotional feeling states being associated with visceral and other bodily responses (body loops) to certain contextual situations. According to this theory, these body loops, or their meta-representations in the orbitofrontal cortex (OFC), may play a part not only in how somebody feels at a given moment but may also influence future planning and intuitive decision making. For example, according to Damasio, somatic markers may covertly result in “undeliberated inhibition of a response learned previously … [or] the introduction of a bias in the selection of an aversive or appetitive mode of behavior”.

Theories of emotion video excerpt

The embedded video clip below is excerpted from a fall 2017 lecture when I discussed the theories of emotion discussed above.

Limbic system

The limbic system (limbus means rim) is an anatomically imprecise term (coined by Paul MacLean) that nevertheless has stuck around. It was originally described by Broca, and consisted of the cingulate cortex that forms a ring above the corpus callosum and then extends into the temporal lobe.

Papez created a neural model for emotion that focused upon the brain structures that form the limbic system.

A modern version of the limbic system has been devised, which now includes ventromedial PFC and orbitofrontal cortex, the amygdala, and dorsomedial thalamus.

Functional studies of the amygdala

Kluver-Bucy Syndrome

Klüver – Bucy Syndrome – bilateral anterior temporal lobe excision that includes removal of the amygdala – performed experimentally in monkeys.

Symptoms in monkeys:

• Monkeys were “tame” and approached everyone
• Monkeys did not display fear with snakes or with conspecifics
• Monkeys were hyper-oral, put everything in their mouths
• "Psychic blindness" (visual agnosia)
• Monkeys were hyper- and indiscriminatingly sexual (auto, hetero, homo, and inanimate objects)

Human Klüver – Bucy Syndrome has occurred following encephalitis.

Similar symptoms as monkeys

In lecture – I emphasized lack of fear and ‘tameness’ – approaching conspecifics without fear.

fMRI studies of amygdala

Reviewed fMRI experiments that showed that pictures that depicted sad emotions strongly activated the amygdala compared to very similarly constructed pictures that depicted neutral expressions.

Showed that the amygdala response to these task-irrelevant sad pictures was highly potentiated if the subjects had just watched a sad movie clip (deathbed scene in “Terms of Endearment”).

Reviewed fMRI experiment in which a working memory task for faces was interrupted by neutral or emotional distracting pictures. The emotional distracters strongly activated the amygdala, but also deactivated dorsolateral PFC. Subjects performed more poorly on the working memory task with emotional distracters compared to neutral distracters.

This study also used the terms ‘hot’ and ‘cold’ processing. ‘Hot’ or emotional processing activated more ventral frontal regions, while ‘Cold’ or rational processing activated more dorsolateral regions of frontal cortex.

Urbach-Wiethe Syndrome

We discussed in some detail subject S.M., who had bilateral calcification of the amygdala (i.e., no functioning amygdala).

• S.M. had difficulties in imaging and drawing fearful faces.
• S.M. had a very atypical scan pattern with her eyes when viewing faces – she avoided looking at the eyes (similar to what has been reported for autistic individuals). The eyes give a very important cue for fear (we widen our eyes and emphasize the whites of our eyes).
• When forced to look at the eyes, S.M. could detect fear.
• S.M. also had other social deficits – she came up very close to people – invaded their ‘personal space’ by standing too close.

Eyes and Faces

Following upon our discussion of S.M., we noted that humans are the only primates where our eye coloration broadcasts the direction of our gaze and our emotional expressions.

Discussed studies by Whalen showing that the whites of the eyes from a fear expression are sufficient to activate the amygdala – even when presented too quickly for conscious perception.

We also discussed a retinal rivalry task in which a percept switched between a face and a house. Even when the subject only "saw" or was aware of the house percept, the face image (of which the subject was unaware), activated the amygdala.

Discussed a study in which a patient with bilateral occipital lesions from a stroke who was blind, showed activation of the amygdala in response to emotional face stimuli.

Trustworthiness

I reviewed the relationship of the amygdala to judgments of trustworthiness:

• Alex Todorov at Princeton showed that if individuals are asked to judge the relative trustworthiness of two politicians depicted in photographs who ran against each other in an election, the person judged more trustworthy was more likely the winner of that election.
• In a different study than that above, Todorov had a large population of subjects rate the trustworthiness of pictures of individuals who were portraying neutral expressions.
  • When these pictures were later shown to participants in an fMRI study, amygdala activation was correlated with the population trustworthy judgments.
  • Analysis of the pictures that were rated as less trustworthy showed them to be more "male" and more "angry". More trustworthy judgments went to faces that were more "feminine" and more "happy".

Positive emotions

Thus far, the amygdala has been discussed entirely in terms of negative emotions – fear, sadness, etc. Studies by several groups have shown that the amygdala is also activated by positive emotions – we discussed two such studies by Wil Cunningham.

• In one study, Cunningham showed that the amygdala responded more to highly positive and highly negative images than it did to neutral images.
  • This suggests an ‘intensity’ model of emotion in the amygdala.
  • However, it appeared that the response to positive stimuli was somewhat less than to negative stimuli – suggesting that the amygdala is predisposed to respond to negative valence.
• In a second study, Cunningham examined the amygdala's response to emotional stimuli as a function of subjective happiness trait. People with high subjective happiness responded just as strongly to negative valenced images as did people low in subjective happiness. So – high subjective happiness people do not look at the world through rose-colored glasses. However, the high subjective happiness people responded more strongly to positively valenced stimuli than did subjects low in subjective happiness.

New controversies

A 2017 article by Pare and Quirk has challenged the central role of the amygdala in emotion. Pointing to the original Kluver and Bucy findings, these authors emphasize the movement component of the behaviors (i.e., the approach behaviors) rather than the emotional aspects. Using neural recording data from rats embedded in more naturalistic settings, the demonstrate that many amygdala neurons fire (or don't fire) when movements occur, but not when threats occur. They propose that amygdala firing is related to behavioral engagement; i.e., approach and avoidance behaviors. It is easy to see how approach and avoidance behaviors are related to emotion. This controversy will undoubtedly result in more studies being conducted in the next several years to clarify and resolve these issues.

Emotion again

So how is emotion represented in the brain?

• We have some weak evidence for the categorical theory of emotion – in that the insula appears activated by disgust, and (thus far) not by anger and other emotions (although see later about social emotions, such as empathy).
• However, the amygdala seems to respond to most, if not all, emotions – and it responds more vigorously with increasing emotional intensity.

Videos

The following videos were prerecorded for 2020.

Previously recorded live lectures.

The video embedded below was recorded in Fall, 2019.