As we go along, just keep in mind Pessoa's thesis of the highly distributed and networked brain. Independent functions do not singly map onto spatially isolated parts of the brain. Instead, a many-to-many function-to-structure mapping is involved. As you'll see, while we'll start with emotion and motivation, the subcortical areas discussed are heavily implicated in many more diverse functions.
Some historical context
Pessoa starts off with a historical view of brain research on emotions. During the late 19th century (and even today), it was common to hold a hierarchical view of the brain, one where more complex structures were built on top of more rudimentary ones, thanks to the mechanisms of evolution. Combined with Darwin's belief that reason was a more advanced faculty that reigned supreme over more primitive and basal functions like emotion, many thought that the former mainly resided in superior (i.e., towards the head) brain regions, whereas the latter was the function of more inferior (i.e., towards the feet) regions.
And experimental evidence seemed to confirm this belief. For instance, Friedrich Goltz decorticated (i.e., removed the cortex of the brain... yikes!) dogs to see how it would affect their behaviour. He observed that, while the dogs typically remained unnaturally still, they often displayed episodes of uninhibited rage. Naturally, this led many to believe that subcortical regions played a defining role in emotion production. Now that we're caught up on the context in which research on emotion was conducted, let's look at some key areas implicated in emotion production, starting with the hypothalamus (see Fig. 1).
Fig. 1 A few subcortical structures (Pessoa, 2022)
The hypothalamus
Emotions and sham anger
The link between the hypothalamus and emotion production was made explicit by Cannon & Bard, who, back in the early 1900s, decorticated cats and observed similar uncontrolled anger reactions found in Goltz's dogs. Subsequently, they made various lesions around the subcortical areas to see which would eliminate this emotional response. This happened when the posterior hypothalamus was lesioned, which led many to conclude that the hypothalamus was the key subcortical structure responsible for emotion production.
One key aspect of this finding is often neglected, however. The anger response observed in the decorticated cats is very specifically termed 'sham anger'. Given that 'sham' can be defined as a trick or a hoax, it suggests that the anger response observed wasn't real at all. Indeed, while the cats showed aggressive and defensive behaviours, this anger response wasn't consistently directed toward the triggering stimulus. In some sense, it seemed like they were showing anger behaviours without necessarily 'feeling' anger per se.
This analysis is elaborated upon by Pessoa, who points out that by and large, emotion can be described as having 2 components, namely a subjective experience and an observable action. While we can very directly observe actions, it is extremely difficult to gauge the subjective, first-hand experience of emotions. Here, Bard was careful to distinguish the actual emotion of anger from the 'quasi-emotion' of anger displayed by the cats, a distinction often overlooked by many. This begs the question, can the hypothalamus really be characterised as the main causal piece behind emotions, or are we only looking at one piece of a complex puzzle?
Other functions of the hypothalamus
Emotions aside, the hypothalamus is also involved in many other important functions. For example, it is heavily involved in autonomic functions, that is, functions that don't require conscious control on our part. These include functions involving the sympathetic division of the autonomic peripheral nervous system, such as the 4 'F's (fight, flight, fright, and sex), as well as those associated with the parasympathetic division, such as homeostatic regulation, digestion, and immune responses.
One specific function Pessoa describes in detail is that of the stress response, which involves the hypothalamic-pituitary-adrenal (HPA) circuit in the brain and body. Unsurprisingly, this circuit heavily implicates the hypothalamus, the pituitary (a gland located in the brain), and the adrenal gland (situated on top of our kidneys). When one is stressed, the hypothalamus receives and integrates neural signals from different brain regions, which activate the neuroendocrine (i.e., involving neural signals and chemical hormones) stress response.
Briefly (see Fig. 2), this response involves hormonal release from the pituitary (e.g., corticotropin-releasing hormone or CRH, and adrenocorticotropic hormone or ACTH), which leads to the release of stress hormones (i.e., glucocorticoids, such as cortisol) in the adrenal gland. Very much like a negative feedback loop, stress hormones then play a role in suppressing hypothalamic and pituitary responses, thereby preventing prolonged stress responses that can place a strain on one's physical health.
Fig. 2 The HPA stress response (Pessoa, 2022)
Bidirectional connections abound
Just like how superior cortical areas are thought to exert some level of control over more inferior subcortical regions, Pessoa points out how many also believe that the hypothalamus is involved in descending control, that is, it acts as a central control of brain regions located further down the brainstem, as well as of the spinal cord. In this view, the hypothalamus is responsible for sending out signals to these areas, which tell them exactly what they should be doing.
However, this presents a limited view of the hypothalamus, or any brain region for that matter. The hypothalamus is actually involved in many bidirectional connections with other brain areas (including both subcortical AND cortical areas)! This means that not only are they sending out signals, but the hypothalamus regularly receives inputs. In other words, like many brain regions, the hypothalamus is involved in signal distribution and integration (see Fig. 3). This is likely one of many reasons why the hypothalamus is involved in a huge array of functions, including emotion production and the many varieties of autonomic response!
Fig. 3 Signal integration and distribution (Pessoa, 2022)
The amygdala
Learning fear & responding with fear
Let's move on to the amygdala (see Fig. 4), which is an almond-shaped structure found in the subcortex of the brain. While early stimulation studies found that this region was involved in autonomic processes, the amygdala is more well-known for its role in learning fear and producing fearful responses. One way to study this is through the classical conditioning paradigm, where researchers might, for example, repeatedly present rats with a neutral tone and electric shock at the same time, thereby producing a fear response in them. After some time, the tone is presented alone without the shock, and still produces the same fear response among the rats, including freezing or startled behaviour and the release of stress hormones.
Fig. 4 The amygdala (Pessoa, 2022)
The amygdala is proposed to be highly involved in the association between the unconditioned (i.e., the electric shock) and conditioned (i.e., the tone) stimuli. On the one hand, the basolateral amygdala (see Fig. 4) is highly interconnected to different cortical areas (see Fig. 5), from which it receives sensory stimuli and facilitates the connection between the unconditioned and conditioned stimuli. On the other hand, the central amygdala (see Fig. 4) is responsible for producing the fear-related responses observed. This is facilitated by its rich bidirectional connections with subcortical and brainstem areas (see Fig. 6), where it is involved in modifying the availability and distribution of neurotransmitters (e.g., norepinephrine, dopamine, serotonin, acetylcholine) throughout the brain.
Fig. 5 Patterns of amygdala anatomical connectivity (Pessoa, 2022)
Fig. 6 Connections between the amygdala and subcortical areas (Pesso, 2022)
The role the amygdala plays in fear responses is illustrated best through patient SM, who, with a complete natural lesion of their amygdala, is largely unable to experience fear. The one exception was when they were made to breathe in large amounts of CO2. This special case suggests that there are multiple fear pathways in the brain. For instance, CO2-related fear is thought to depend on extra-amygdalar pathways, such as those involving the periaqueductal gray (PAG). The lesson for us is that while the amygdala might play an important role in experiencing fear, it is not the only region implicated, lending support to Pessoa's picture of a highly complex and distributed brain.
Responding to fear
Using fMRI, the amygdala has also been shown to respond more strongly to emotionally-laden images and facial expressions (e.g., fearful vs. neutral faces). Using masking and attention-manipulation studies, there has been a strong push toward understanding the amygdala response as an automatic process independent of conscious awareness. Pessoa thinks otherwise. While I'll leave out the details, he essentially argues that the results that led to the conclusions above are due to methodological flaws that don't take into account, for instance, how challenging an attentional task is or participants' tendency to give one response over another when faced with uncertainty.
Other functions of the amygdala
Like the hypothalamus, the amygdala is involved in more functions than merely fear processing. Indeed, there is increasing evidence that the amygdala is also implicated in reward processing, and supports conditioning not just for averse stimuli, but also for positive ones! Additionally, Pessoa suggests that more broadly speaking, the amygdala is responsible for choosing the most important bits of information to act on from a diverse range of possible options. Or in other words, the amygdala contributes to decision-making.
For example, studies where participants are given 2 choices (one that provides instant gratification, and the other that grants delayed rewards) show that activity in the amygdala predicts whether or not the individual chose to spend or save. While preliminary, Pessoa argues that this provides some initial evidence that the amygdala contributes to decision-making, a function that is more commonly attributed to the prefrontal cortex.
Concluding remarks
There is no doubt that the hypothalamus and amygdala play important roles in their commonly attributed function of emotional production and regulation. That being said, not only are there many other structures involved in these functions, but these 2 subcortical structures also contribute to many more diverse functions. This is what I suppose Pessoa is trying to get across -- the rich networks between brain regions necessarily push us away from modular one-to-one function-to-structure mappings, and toward more complex many-to-many mappings. In the next post, we'll round out the final part of this chapter by looking at subcortical involvement in motivation.
References
Pessoa, L. (2022). The entangled brain. Journal of Cognitive Neuroscience, 35(3), 349–360. https://doi.org/10.1162/jocn_a_01908
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