Social Neuroscience

Goals

To discuss the anatomy and function(s) of the cingulate cortex
To discuss of the neural basis of empathy
To discuss oxytocin – a neuropeptide associated with affiliative behaviors
To discuss Theory of Mind and its neural basis
To discuss alternative formulations of Theory of Mind – set shifting and self-projection

Topic slide

Tania Singer (b. 1969) is the director of the Department of Social Neuroscience at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany. Singer has conducted path-breaking research in social decision-making.

David Premack (1925-2015) popularized the study of Theory of Mind in his famous 1978 paper Does the Chimpanzee have a Theory of Mind.

Reading

Reading: PCN Box 24A (pp. 555-556), also pp. 784-787.

The limbic system redux

I reviewed key functions attributed to the different anatomical regions that comprise the limbic system. I reemphasized that the term limbic system is imprecise with respect to anatomy, but nevertheless widely used to refer to brain processing in these 'rim' cortical regions that has an affective/emotional component.

Cingulate cortex

Cingulate cortex is anatomically and functionally inhomogeneous:

Parts of the cingulate cortex are considered by anatomists to be 3-5 layered paleocortex and not six-layered neocortex.
Cingulate cortex is not anatomically homogeneous, rather it can be divided on cytoarchitectonics and connectivity into an anterior, mid, and posterior region. Within these three areas, there are also anatomical differences.
Cingulate cortex is not functionally homogeneous. Many prior studies have emphasized that both pain and emotions appear to activate the mid-cingulate and anterior cingulate, respectively.
There are strong motor connections from the mid-cingulate to the corticospinal tract, and there is also a 'cingulate motor area'
The anterior (ACC) and mid-cingulate (MCC) regions show strong connectivity to the anterior insula. Indeed, many studies that activate the ACC and MCC also activate the anterior insula.

Cingulotomies

In the late 1940s, a new psychosurgical operation – the cingulotomy – was introduced with the hope of achieving the therapeutic goals of the prefrontal lobotomy without the side-effects. This surgery was initially targeted at chronic pain – particularly pain that had a strong emotional component. Unlike the prefrontal lobotomy, the cingulotomy is still performed widely today (in a recent review, it was stated that more than 1000 cingulotomies have been performed at Massachusetts General Hospital since 1962).

The operation is normally performed on individuals who have no options left with regard to pain cessation. The clinical outcomes of cingulotomy for chronic pain is mixed and the methods for measuring outcome vary considerably. It appears, however, that about half of patients receive a substantial benefit. Interestingly, many patients report that the pain is still objectively present, but that it no longer is the focus of their attention, or has the strong emotional component.

Reviews of the efficacy of cingulotomies for chronic pain indicated that the procedure worked best in patients who had comorbid anxiety, depression, or obsessive compulsive tendencies. This result led to the operation being used in these patient populations.

You can read more about cingulotomies here on Wikipedia. For those interested in 'circuit-based' psychosurgical approaches to obsessive-compulsive disorder (OCD), here is a link to a recent review paper.

Empathy

Empathic behaviors

What are empathic behaviors?

Imagining how another is thinking and feeling
Imagine other – projection
Empathetic attentional set w/o losing oneself
Imagining how one would think and feel in the other’s place
Role taking, perspective taking
Feeling distress at witnessing another person’s suffering
Empathic or personal distress
Feeling for another person who is suffering
Pity or compassion

Researchers have drawn distinctions among different forms or types of empathy:

Knowing another person’s internal state, including her thoughts and feelings
- Cognitive empathy
  - This does not imply that this knowledge imparts a ‘feeling’ in the observer – the latter would be emotional empathy.
Adopting the posture or matching the neural responses of an observed other
Coming to feel as another feels
- Emotional contagion
Intuiting or projecting oneself into another’s situation
- Aesthetic empathy

Physical and social pain

I revisited our prior discussion about how experienced pain and observed pain in others activate some of the same brain regions including:

Insula
Anterior dorsal cingulate cortex

The consistency of the cingulate and insula imaging findings was highlighted in a recent meta-analysis of imaging studies conducted by Lam and Singer.

A study by Naomi Eisenberger (UCLA) showed how social isolation (i.e., social pain) manipulated by the Cyberball game also activated many of the same brain regions (insula, anterior dorsal cingulate) as activated by physical pain.

Pain, and the activation of the brain regions discussed above are altered when a loved one holds hand, or when one holds a picture of the loved one. That is, the activation by pain is socially modulated.

Take two Tylenol and call me in the morning…

It has been reported by several groups that social pain can be ameliorated by taking anti-pain medications – specifically Tylenol (aceptaminophen). (It is not clear whether this result obtains for NSAIDs, like ibuprofen).

Tylenol influences the same brain areas as activated by social isolation. A recent study reports that taking Tylenol also reduces one's empathy for the pain of another.

Empathy and Fairness

The neural substrate of empathy involves some of the same areas we discussed in the context of pain and empathy – namely, the dorsal anterior cingulate cortex (dorsal Acc) and the insula.

I discussed in detail a 2006 Nature study by Tania Singer and her collaborators, in which empathy and fairness was studied in a Trust Game (PDG):

Subjects were manipulated during a Trust game to classify the individuals with whom they played as fair or unfair individuals.
- The precise game played was a sequential 'donation' version of a Trust for you aficionados of economic game playing.
- The subject was given 10 dollars and could contribute a portion of that to one of two confederates. Once donated, the value of the 'donation' was tripled.
- The confederate could return a portion of the tripled donation back to the subject.
- The 'good' or 'fair' confederate generously rewarded the subject while the 'bad' or 'unfair' confederate did not.
The fair and unfair confederates were rated on a variety of scales, and it was shown that the subjects 'liked' the fair confederate and did not like the unfair confederate.
The brain’s response to watching unfair players be shocked was lower than watching the fair player be shocked.
- This was particularly true in male subjects who showed no empathetic brain response to unfair players being shocked. Female players showed a definite, but muted, brain empathetic response to unfair players being shocked.
- The brain response was linearly related (across subjects) to empathic concern scores.
In male participants only, the n. accumbens was activated when watching an unfair player be shocked – the suggestion is that the participants found the punishment of the unfair players to be rewarding (as we had previously discussed the activation of the n. accumbens to rewarding stimuli in the decision-making lecture).
- The response of the n. accumbens in males was proportional to their 'revenge' composite score.

Motor mimicry

Depending upon time, I may not cover this topic in lecture.

I described an example of motor mimicry in which unconsciously perceived (through visual masking) emotional face expressions caused electromyographic (EMG) activity in the eye muscles appropriate to produce the emotional face expression. Another ‘mirror’-like behavior.

A common network for the inhibition of imitative behavior, self–other distinction and theory of mind

Brass, Spengler and their colleagues have compared motor mimicry to other measures of self-other distinction and theory of mind. Their interest was in motor mimicry – the automatic tendency to mimic the movements of others. However, sometimes the automatic mimicry response must be suppressed – for example, you don't want to automatically return a smile in the context of a funeral.

Researchers have studied what brain regions are critical for resisting motor mimicry. I provided an example of a task used by some of these investigators, in which a subject must raise one of two fingers in response to a number cue (1 or 2). In some conditions, the subject watched a video of the a finger moving while the number cue was presented. The idea is that watching the finger move would cause automatic mimicry in the subject's finger. When the finger moved on the video was not compatible with the number cue, the subject would need to resist the tendency to mimic the movement of the finger on the videotape in order to respond correctly to the cue. The measure analyzed was interference due to resisting mimicry (the difference between responding to the number cue in the context of a congruent and incongruent finger movement on the videotape).

Performance on the resistance to mimicry task was correlated with a Theory of Mind (TOM) task in which the subject listened to a story that involved either the mental or physical state of another individual and answered questions that revealed whether the subject thought about the individual's state of mind. That is, subjects who had difficulty in resisting mimicry performed poorly on the TOM task.

Oxytocin

Oxytocin is a neuropeptide produced in the Paraventricular nucleus of the hypothalamus. This is the same nucleus of the hypothalamus that releases corticotrophin-releasing hormone (CRH), which initiates activity in the HPA axis. Oxytocin has targets throughout the brain – and prominently in the n. accumbens and the amygdala.

Voles

I discussed the prairie vole and montane vole experiments by Young and Insel at Emory:

Prairie voles are monogamous and affiliative, spend much time with mates, and have high levels of oxytocin receptors.
- Blocking oxytocin in the region of the n. accumbens
Montane voles are neither monogamous nor affiliative and have low levels of oxytocin receptors.

Intranasal oxytocin delivery

Oxytocin can be increased in the brain through a nasal spray, and so many experiments compare individuals or groups with, and without, augmented levels of oxytocin.

Social vs. Non-social task performance

I described a study in which subjects performed two very similar tasks – but one used arbitrary colors as stimuli (non-social task) while the other used social stimuli (faces).

Oxytocin enhancement improved performance in the social task, but not the non-social task.
Oxytocin did NOT help twins with bilateral amygdala calcification perform the social task (the same disorder as patient SM discussed earlier in the lecture on emotion and fear in the amygdala) Thus, it was concluded that an intact amygdala is necessary for oxytocin to work.
Oxytocin did not improve cognitive empathy – subjects could identify emotion depicted in photo. However, oxytocin increased emotional empathy – subjects felt more of an emotional response when viewing emotional photos.

Oxytocin and Parochial Altruism

I discussed in detail an experiment by DeDreue from 2010:

Used a monetary version of the Prisoner’s Dilemma Game (PDG). The PDG payoff matrix was manipulated in three different experiments.
Subjects were given money. They could keep the money, could contribute to their in-group where all in-group members benefitted, but they themselves got less than they contributed (in-group love result), or they could contribute to their in-group as above, but where the out-group would also lose money (out-group hate result).
- In this experiment, hurting the out-group was entirely gratuitous; the out-group did not influence what the in-group earned. The results showed that oxytocin nasal spray increased in-group love, but NOT out-group hate.
In a later Prisoner's Dilemma Game experiment, the out-group’s decision COULD hurt the in-group earnings. For example, on some trials, the payoff matrix was adjusted so that if the out-group defected, it would cost the in-group a large penalty (high fear matrix). On other trials, the payoff matrix was adjusted so that if the in-group defected, it would cause a large benefit to the in-group (high greed matrix). In this experiment, oxytocin nasal spray increased out-group aggression – interpreted as defensive aggression. That is, oxytocin made individuals more likely to defect in the high fear group to avoid a potential loss to the in-group. Oxytocin did NOT increase the tendency to defect in the high greed matrix when fear was held low. This was interpreted as indicating that, under oxytocin, the in-group players engage in defensive aggression against the out-group, because the out-group posed a threat to the in-group.

Common variants

The oxytocin gene has two common variants (or, alleles):

GG (one G from each parent) are more ‘prosocial’
AA (one A from each parent) have greater stress reactivity (bigger startle response), less prosocial

Oxytocin and autism

Oxytocin influences – normalizes – some social task performance in Autistic individuals. I used an example of a modified cyberball game in which a subject played with two avatars. One (good) avatar would reciprocate and occasionally throw the ball back to the subject. The other (bad) avatar would never throw the ball back to the subject.

Over trials, typically developed subjects would learn not to throw to the bad avatar, but autistic individuals would not learn. However, when treated with oxytocin, the autistic individuals would learn not to throw to the bad avatar.

Theory of Mind

Does the Chimpanzee have a Theory of Mind?

I discussed Premack’s 1978 paper and reviewed some data he presented that indicated that chimpanzee’s have a good appreciation of another’s goals. The chimps demonstrated this by choosing an appropriate object that would solve the dilemma posed in a video. For example, if the chimp watched a movie of a human stuck in a cage, the chimp would select a ‘key’ as the correct object in a forced choice task with an incorrect object for the task.

The issue of whether non-human primates have a theory of mind is still contentious. Indeed, a study was published in fall 2019 that addressed this issue, and argued that apes use their own experience to guide their projections about another’s action. The video presents the gist of this recent study.

Human neuroimaging studies of Theory of Mind

I discussed studies by Saxe and by Gallagher that studied Theory of Mind in humans using fMRI. Saxe’s studies used TOM stories in which the participant would need to understand what another human must have surmised in the scenario in which that other human was a participant. These stories were compared to control stories that involved mechanical inferences or movement.

I then reviewed an online 'meta-analysis' I conducted using the Neurosynth.org database which identified 181 TOM studies. The TOM tasks activated the several brain regions more than control tasks. Of particular interest, invoking TOM activated the temporoparietal junction (TPJ), ventromedial PFC (vmPFC), medial frontal cortex, and PCC.

Alternate views to TPJ and TOM

The overlap of brain activations observed in different cognitive/social/affective domains has become apparent to many investigators. There has been interest, thus, in divining the fundamental function of a brain region, or coordinated network of regions, that may be common to all of the different tasks used to activate a region or network of regions.

The TPJ is a brain region with a somewhat imprecise anatomical definition that overlaps other brain regions, in particular the posterior superior temporal sulcus (pSTS). The pSTS region has been shown to strongly activate to biological motion. I provided in lecture the example of point-light-walker.

However, the context of biological motion matters – eye gaze shifts differentially activated the pSTS. Illustrated a study in which an observer watched an avatar walk towards her. Approach shifts (eyes shifted toward observer) activated pSTS more than shifts away from the observer (eyes look away from observer).

I briefly discussed the fact that of apparent overlap between the TPJ regions activated in TOM tasks, and the areas activated as part of the ventral attention network, and areas activated by biological motion tasks.

Biological motion often invokes an assessment of another’s goals and intentions. That is, when we watch somebody move, we make inferences about what that person’s goal is. Perhaps biological motion perception is a key component of a more general TOM mechanism.
The ventral attentional network is engaged as a ‘circuit breaker’ where attention is switched from one task to another. Perhaps TOM requires one to switch between perspectives (the observer’s perspective, and the perspective of another human) in a way that calls upon the same neural mechanisms as are engaged in attention switching.

Self-projection

Buckner and Carroll considered the overlap in fMRI activation studies of prospection (thinking about the future), theory of mind (thinking about others) and navigation (involving planning and episodic memory). The proposed that self-projection (mentally projecting oneself into an alternative situation) was the fundamental concept unifying these concepts and leading to the activation of the TPJ and mPFC.

It is notable that Buckner and Carroll's concept of self-projection bears some similarities to Freeman and Watt's concept of projecting the whole individual into the future. For convenience, I have copied the quote from last lecture below.

“…the rest of the frontal cortex is, according to our hypothesis, concerned with the projection of the whole individual into the future. With the intact brain the individual is able to foresee, to see before, to forecast the results of certain activities that he is to initiate in the future. And he can visualize what effect those actions will have upon himself and upon his environment.

What is interesting in both Buckner and in Freeman's conceptualizations, is that the individual projects herself into her own mind in some alternative situation (i.e., 'how will this situation look to me if I were involved') rather than the mind of another. However, the strong overlap of activated areas for self-projection and TOM suggests a common substrate.

The Human Brain

Professor Gregory McCarthy

Lecture 25