Well, that's all that I intended to say regarding the expression of the emotions. The the motivation of our somatic and visceral motor effectors. Let's move on now and talk about how the content of emotion is integrated with other dimensions of cognition, and can provide some significance to the context in which we are integrating our experience of the moment. So this really brings us to our two key brain systems for learning these associations that I've been describing between primary and secondary reinforcers. These two brain systems would be the Amygdala and the Orbital-Medial division of the Pre-Frontal Cortex. So, let's take a closer look at the Amygdala, consider its structure and then some of its functional properties that pertain to emotional experience and expression. So, as I've reminded you in a recent tutorial, the amygdala is a mass of grey matter that is found in the anterior and medial part of the temporal lobe. Now, the amgdala is largely anterior to the hippocampus and the temporal horn of the lateral ventricle, but there is a little bit of a region of the posterior amygdala that overlaps with the hippocampus. But for the most part, think of the amygdala as anterior to the the hippocampus in the medial part of the temporal lobe. Now, as we look at the amygdala, we see that it is a true complex. It's not just one mass of cells, but there are many subdivisions to this region. There is a cortical region to the amygdala. and this is, in fact, the cortex that we see protruding into that structure called the uncus on the medial aspect of the parahippocampal gyrus. There we find a collection of subdivisions that we call the medial group. Now just lateral to that medial group in a region that we sometimes call the temporal stem, it's a region of the brain where the temporal lobe attaches to the posterior frontal lobe in the overlying insular region. This is where we find the central group. So, the central group of nuclei is quite important, providing the output from the amygdala into the medial part of the hypothalamus. But by far, the largest division of the amygdala in the human brain is this basal-lateral group of nuclei. So, we could further subdivide this, but for our purposes we'll just consider this collectively as the basal-lateral amygdala. This basal-lateral group of nuclei in the amygdala maintains extensive connections with the orbital and medial part of the prefrontal cortex. So, there are strong bidirectional interactions that happen between these two [UNKNOWN] cephalic regions that are so important in the experience and expression of emotion. But there are also less direct projections between the amygdala and this orbital and medial prefrontal cortex that run through the base of ganglia. So, the amygdala is a very prominent source of inputs to the nucleus accumbens, and other components of this ventral striatum. the ventral striatum in turn projects to ventral pallidum, substantia nigra pars reticulata and from there those palatal structures send outputs to the medial dorsal nucleus of the thalamus. So, this is the specific thalamic nucleus that then gives rise to projections up to this orbital/medial prefrontal cortex. So, there's something of a, of a triangular relationship here between the amygdala, the mediodorsal thalamus and then the orbital and medial prefrontal cortex. And these structures can interact in various ways that we suspect are, are quite important for triggering emotional experience and expression. And let's not forget about the role of the basal ganglia in all this. The basal ganglia is likely involved in producing a shift in the experience of emotion, and this might be consistent with the processing of a reward signal, or a signal that predicts the experience of reward. Now, the centrality of the amygdala for learning the associations that produce emotion has been made much more clearer from the use of animal models that have studied one particular dimension of emotional experience. And that is the emotion of fear. So, in laboratory studies of fear conditioning, we've come to understand how the amygdala is really the key site for associative learning. So, here's how these experiments typically go. So, there is a innocuous tone presented to a laboratory animal, and that tone is really neither particularly pleasant nor aversive to the animal, we imagine. it's just a neutral sensory stimulus. Now, that auditory stimulus is going to be processed of course by our auditory pathways which lead into the auditory thalamus, the medial geniculate nucleus. The medial geniculate nucleus then projects to the auditory cortex, which relay signals into the amygdala. Now, interestingly, this medial geniculate nucleus also has direct access to the amygdala. So, we imagine that while the cortical relay provides a more highly processed, more integrated sense of that stimulus, this direct projection from the thalamus to the amygdala, is more of a very fast, kind of crude signal that is indicating the presence of that stimulus. Not necessarily details about the tonal structure of that stimulus, but rather simply just the presence of the stimulus. Now, there are other projections into the amygdala from all other sensory systems, including those that would detect the presence of a noxious stimulus. Now, imagine if that auditory tone is paired with something that the animal finds unpleasant. Perhaps a brush to the underside of the animal through the floor of a cage for example, or maybe a mild electrical shock applied to the floor of the caging. Well, this is a kind of aversive stimulus that we might consider to be a primary reinforcer, in this case, a punisher. Well, the amygdala is going to be receiving input from these other sensory pathways, somatic sensory pathways in this case. So, we imagine that this is going to be a very strong signal into the amygdala, that might be initially be paired with a relatively weak signal. And the pairing of these two inputs in time and in space, that is within the dendritic arbors of these neurons of the amygdala, results in associative learning. And as a consequence the auditory tone now grows in its strength and its impact on amygdala neurons. The output of these amygdala neurons then is going to impact somatic and visceral motor activity, and produce behavior consistent with fear and anxiety. Now, after some period of pairing these two kinds of inputs, the auditory stimulus and the aversive tail brush or electrical shock to the feet. This is going to produce the behavior associated with fear in this animal, with the sole presentation of the auditory tone. So this is really one of the chief cellular examples that we have of emotional associative learning. And we know that something like this is taking place because we can impede this process by blocking NMDA glutamate receptors. which is suggesting that something like long-term potentiation is mediating this associative learning here among these amygdaloid neurons. We also know much more about the detailed circuitry that's involved in mediating the expression of this fearful behavior. And how that's processed through intrinsic networks within the amygdala, and then eventually via the output of the central group of nuclei to the medial hypothalamus and brain stem. Well, I think that this has been a wonderfully productive model. But some have questioned its relevance to human emotion. especially human fear. But I think that the relevance is real and compelling. In large measure, because of studies of one particularly instructive patient, who has come to the medical literature in the last couple of decades, and has been studied extensively with a group based at the University of Iowa, here in the United States. And this group has done just a heroic set of studies of this particular patient in characterizing her impairments in her emotional life, but also in her everyday real life experience in the real world. While this is a patient that is known in the literature as Patient SM, or Patient SM-046. Patient SM has been diagnosed with a condition that has led to the bilateral calcification, and atrophy of her anterior and medial temporal lobe. And in particular, it's led to the bilateral destruction of much of her amygdaloid complex. However, this condition has spared the surrounding neocortical regions, and importantly, has spared the hippocampus. So patient SM has really provided a rare opportunity to explore the impact of a selective lesion of the amygdala with sparing of surrounding portions of medial temporal lobe. What was quite obvious in the initial evaluations of this patient is that, she showed no primary sensory or motor deficits. And she performed quite well on what was at the time, the standard battery of neuropsychological tests, yet she had real problems in her daily life. And the challenge to the investigators was to come up with a better means of testing her functions in the clinical setting that would resemble real life experience. So, they decided that they would really focus on the capacity of this patient to read emotion in the human face. And so they did a series of studies that were reasonably well-controlled. They compared her performance to the performance of a group of patients that had injuries to their brains, but outside of this medial region of the temporal lobe. And what they did was, they asked patients to rate the content of various primary emotions such as surprise and sadness, and anger, and disgust, and fear in the presentation of portrait views of the human face. And what we're seeing here in this plot is simply a a way of qualifying the ratings of these various primary motions that these subjects recognize across is inventory of photos. What you see in the bold orange line is the ratings of fear that were present in this inventory of human faces. Now when patient SM was asked to do the same, these were her ratings. So, you can see that she did quite well on ratings of let's say anger and disgust and happiness. her ratings of sadness were likewise pretty high and, and relatively normal. for some reason, her surprise was somewhat down. But clearly, the one emotion that she really struggled to rate and recognize in the human face, was fear. So, in this bold orange line, that's her rating of fear in the same inventory of human faces. Now, these investigators went on to study various dimensions of patient SM's life. And fairly recently they utilized mobile technology and they asked her to respond to a, a short survey that asked her to reflect and introspect, and rate her experience of various emotions at different times of day over about a three months period. And, what we're looking at here are her responses to these various prompts about her ratings of her emotional experience. And the scale here is a percent of the maximum possible performance that she might have displayed across these various dimensions of emotion. And what's very clear is that she hardly ever at all, self-reported experiences of emotions that we might consider associated with fear. Now there's really a fascinating set of papers that I would encourage you to read if you are interested in learning more about patient SM. In short, she appears to be an individual that is impaired in her ability to read fear in the human face. And consequently, she appears to be severely impaired in the actual experience of fear in day to day life. I think what we've learned from patient SM is that, in the human brain the amygdala is an important center for the experience and expression of emotion especially the emotion of fear. Well, why might this be helpful in everyday life? Well, I think, we're learning more about the basis of social cognition and how it relates to brain systems. And what's become clear is that the amygdala, and its role in our emotions is very important in mediating various aspects of social cognition. One important aspect of social cognition that's relevant is our evaluations of the trustworthiness of another human being. So, what's being shown here in a very clever set of experiments is the activity of the amygdala when human subjects are evaluating human faces. And the evaluation instructions are either explicit about making a determination about trustworthiness, or the evaluation is implicit. That is, the participants in the study are direct to make some other differentiation, such as whether the faces are of university students or secondary education students. But in both cases, what we see is a clear relationship between activation in the amygdala left and right, and judgments of a person's face being untrustworthy. So, what's very clear in these data is that, when amygdala activity is high, our judgments of trustworthiness are low. That is to say, if we're in a social situation and interacting with an individual, and we're beginning to believe that we might not want to trust this person. That sense of not wanting to trust seems to be associated with elevated levels of amygdala activity. Now, I think it's fair enough to think of the amygdala as our brain's early warning system, that it's providing us with a sense that something just might not be right. It's not necessarily signaling anxiety or even fear, but rather it's increasing vigilance. So that we can attend to the rich array of sensory stimuli that are defining the nature of this interaction that we might be having. So, let me try to summarize what I've said so far about the amygdala. So, the, the amygdala clearly plays a primary role in the association of sensory stimuli with reward and punishment. But I think more generally the amygdala has an important role to play in cognition. The amygdala modulates information processing in the fore brain, and it has an impact on our perceptual systems. It can enhance the awareness or attentiveness of our perceptual systems to aversive or arousing stimuli. The amygdala can have an impact on memory, on our mnemonic systems. It can enhance memory for emotionally charged events. Now, this provides us with a framework for thinking about what might happen when there's not enough signalling coming out of the amygdala, or perhaps when there's too much. So, with insufficient amygdala activation or amygdala hypofunction, we can expect there to be deficits in the efficacy of information processing. Perhaps this helps us understand Patient SM. So, the sensory signals are being processed, but she's simply not attending to them in a way that would impact her judgments about potential threat. So, we imagine in patients like SM, the early warning system is defective. It's not going off, it's not signaling the need to have a heightened sense of vigilance. To have directed attention about the sensory stimuli that might be very significant in giving us clues about the nature of the social interaction with which we are engaged. As a consequence, patient SM and perhaps others like her, have been the subject of violence, of domestic abuse. So I can imagine that living without the brain's early warning system might put one at risk in a variety of social circumstances, where the intentions of other people are not always so clear. And it requires reading these emotionally nuanced signals in order to inform our judgements of trustworthiness. Now, there are also problems with amygdala hyperfuntion, that is, when there are too many signals coming out of the amygdala. Imagine what it might be like to be living with an overactive early warning system. As a consequence, we might expect there to be excessive vigilance, perhaps even anxiety, or perhaps even over fear.
