Cortical subcortical integration and decisions: An amygdala-prefrontal cortex neural circuit case study

July 7, 2022 at 8:32 AM
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Cortical subcortical integration and decisions: An amygdala-prefrontal cortex neural circuit case study

Vanessa Nyblom UA ’25 and Jim Stellar

In experiential education, college students integrate the limbic or emotional logic of a direct experience, such as an internship, with their academic and more cognitive plans, such as their coursework and chosen major.  How does that happen?  And especially consider the widely held belief that this emotional logic is largely invisible to the cognitive logic, except as an output or summary judgment (e.g. I really like that job).  This is the basis for another widely held belief that reflection upon experience alone or with a mentor or friends is an important part of taking in the combined cognitive-emotional learning that we believe results in personal growth and career development. We have examined this topic in the last series of blogs, taken from a more neuro-clinical psychology perspective. Here, we aim to explore the finer-grain neural circuitry between the medial prefrontal cortex (mPFC) and the basal lateral nucleus of the amygdala (BLA). The goal in this deeper brain drive to begin to see what can be extracted to a more general level.

Let’s start our exploration with this diagram below from Yizhar and Klavir (2018). This study in animals relates to an anatomical brain scan study in humans where a stronger prefrontal cortex-amygdala anatomical connection predicts a lower level of sub-clinical baseline anxiety, about which we previously wrote.

Notice in the diagram above that the green-colored mPFC projections coming from the BLA region of the amygdala wind up in both the prelimbic (PrL) and infralimbic (IL) regions of the frontal cortex. These neurons from the BLA establish the “upward” part of the projection. In terms of the “downward” projections, the PFC neurons shown from this paper are in purple and come primarily from the IL region of the PFC. Through inhibitory interneurons, shown in black, this projection appears to inhibit the BLA neurons. This creates the first principle of what we see as cognitive-emotional integration – classical and well-known feedback loops.

But one also wants to know from what other places the BLA receives input to be a place where fear learning can exist in the limbic brain. For a little context, other anatomical studies show that the amygdala has about a dozen subdivisions that are organized into three principal major nuclei including the BLA, each with many connections with each other and with other brain areas. Some of these connections so closely connected that neuroscientists have called the system the “extended amygdala.” However, let’s not be put off by the neural circuit complexity – to paraphrase what a wit once said “if the brain were so simple as to be easily understood, we would be so stupid as to understand nothing.” But instead let’s focus on the BLA and stick with the diagram above.

First, not shown in the above diagram, the BLA gets sensory input from all sensory modalities, coming principally from primary and association cortical areas on the same side of the brain and typically using glutamate as their neurotransmitter.  Interestingly, the BLA also gets thalamic sensory input from areas which typically supply the cortex. This projection could give the BLA the ability to connect a sensory stimulus, like a tone or light, with a pain stimulus that is used in classical conditioning of fear and avoidance. As studies show, this input changes the BLA neurons firing in a way that is called Long Term Potentiation (LTP).  This may be what the PFC has to in therapy perhaps in a PTSD (post-traumatic stress disorder) patient to begin to put fear (or anxiety) in its proper place under executive or cognitive control. But there is more. 

Second and also not shown in the above diagram, the BLA gets inputs from the hippocampus, a classical declarative, or fact-and-episode based, memory involved structure and a key spatial learning part of the brain. This could be important in fear learning. 

Third, and the object of the diagram and this blog, the BLA gets inputs from the PFC and other cortical areas.  As mentioned, we focused on this two-way communication here and in previous blogs as a feature of cognitive-emotional integration that is important to clinical insights and into bringing emotional components into insights from experiences like internships in college students who are trying to figure out what will be their careers served by their major areas of college study. 

Finally, the BLA gets input from the hypothalamic area, a key midbrain structure that is involved with feeding and other basic needs as well as sitting just ahead of the dopamine-containing areas of the brain that are involved in movement and reward. 

In this blog, we will not go through the BLA output pathways as that would lose the focus on function and the cognitive-emotional connection thinking here about how emotional experiences, particularly negative ones, can affect experiential learning in normal college students. However, we should mention that many of the places that project to the BLA and the amygdala in general receive projections back. In the case of the hypothalamus and feeding, maybe this pathway is part of the mechanism that stops us from eating when something bad happens and switches us into a predominant fight or flight mode.  Clearly fear has a major effect on bodily systems controlled by the hypothalamus and brainstem such as blood pressure. Maybe even this system stands in contrast with the reward-related systems including eating, that are necessary for survival of the species but come secondary to the more immediate fight or flight needs of the subject.

To return to experiential education, most internships do not result in a fear response.  However, students engaging in internships do make a judgment of how it is going and how it fits with what they imagine are their career plans going forward.  As discussed repeatedly in this blog, what is different about an internship in a college students field of academic study is that the experience is much more engaging and real. Those judgments have a strong and different kind of power over students as they imagine their careers after college.  It is the neuroanatomical components of those judgements and how emotions interact with cognition that is what we want to explore in this blog series and will now move on to consider the other side of a positive-negative evaluation, the accumbens and its relations to the PFC.

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