The Anatomy of the Amygdala

The amygdala is the part of the brain primarily involved in emotion, memory, and the fight-or-flight response. It is one of two almond-shaped cell clusters located near the base of the brain. Together, the amygdalae (plural), also known as the amygdaloid complex, is an important part of the limbic system.

The amygdalae interpret external stimuli like sights and sounds as potentially dangerous and send that information to the hippocampus. This process activates a release of energy so you can respond to and protect yourself from external threats (the flight-or-fight response). The amygdalae are also responsible for assigning values to moments and turning them into memories. 

However, sometimes the amygdalae overreact, perceiving subtle threats like timer or phone rings as though they were life-threatening. This is called an amygdala hijack.

Anatomy 

The amygdalae are complex structures of communication within the limbic system. Variations can have a significant impact on overall brain functioning. 

Structure

The amygdalae are clusters of neurons that typically barely make up 0.3% of total brain volume. Its evolution in human and animal biology is not entirely clear, but research has shown that amygdala size is somewhat positively correlated with a person’s social network and its complexity.

The amygdala contains at least 13 nuclei (masses of nerve cells), which are typically divided into three primary groups:

• Lateral (side) nucleus and basal (bottom) nucleus, also known as the basolateral nucleus 
• Centromedial (center midline) nucleus
• Cortical (outer layer of cerebrum)

Location

The amygdalae are part of the limbic system tucked deep within the brain. The cerebral cortex (outermost portion of the brain) is divided into four major lobes. From front to back is the frontal lobe (associated with cognition), parietal lobe (sensory information), and occipital lobe (visual processing), and under there is the temporal lobe (memory creation and preservation, language recognition, and auditory perception).

The temporal lobe is where your amygdalae reside, just in front of your hippocampus. As an integral part of your limbic system, which is located in both the temporal and bottom of the frontal lobe, the amygdalae are both a connector and communicator sending messages directly to the hippocampus, which relays information to other brain areas, including the hypothalamus (releases hormones), thalamus (relays motor and sensory signals to the cerebral cortex), and cerebral cortex.

Function

The amygdalae are an efficient communicator continuously perceiving, processing, and relaying information between the prefrontal and temporal lobes and the hypothalamus. As such, they act as a manager, assigning emotions like fear or anger to environmental stimuli and triggering the flight-or-fight response.

The amygdalae tell your hypothalamus to communicate with your autonomic nervous system and begin the release of stress hormones that are responsible for the physiological changes associated with fright, panic, and anxiety (such as racing heart, quickening breath, sweating, surging energy, etc.).

The different parts of the amygdala have specific functions, including:

• Basolateral nucleus: Regulates behavioral and physiological responses to stress
• Central amygdala: Plays a role in physiological responses to stress such as fearful, stressful, and some drug-related stimuli
• Extended amygdala (bed nucleus of the stria terminalis): Plays a role in anxiety and stress

The amygdalae also play a role in modulating social cognition and behavior (i.e., recognizing emotion in faces, judging trustworthiness, and generating a sense of personal space). Furthermore, they assign positive and negative meaning to moments, converting them into what we recognize as happy or traumatic memories. This function helps you learn from past experiences and influences future reward-based decision-making.

Associated Conditions

Amygdala dysfunction affects emotional processing, memory formation and storage, and conditional learning, and as such, it is associated with several neurodevelopmental and neurologic disorders as well as psychiatric conditions.

Post-Traumatic Stress Disorder (PTSD)

There is clear evidence of reduced amygdala volume and greater amygdala activation in patients with PTSD. This smaller size has been previously associated with side effects such as stronger fear conditioning and the stress response commonly associated with PTSD.

However, correlation is still unclear, suggesting either a smaller-volume amygdala is a potential risk factor for developing PTSD or a potential consequence of having PTSD.

While not an official treatment, amygdala neurofeedback has been suggested as potentially therapeutic for PTSD patients since it can help individuals enhance their ability to self-modulate brain activity.

Panic Disorder (PD)

Similar to its role in PTSD, some research suggests increased amygdala reactivity and volume deficit play a crucial role in other fear-based and anxiety-related pathologies, including panic attacks and panic disorder. Causes of amygdala abnormal functioning and structuring in PD patients have been linked to brain metabolism dysregulation, as well as genetic variation and early life trauma, and are associated with PD symptoms, including phobic avoidance and irrational worry of panic attacks.

Addiction

Addiction relapse after abstinence happens in part due to drug exposure or exposure to people, places, and things that remind a person of the pleasurable and rewarding effects of drugs of addiction. Research shows this cognitive action of pairing a stimulus (drug) to a behavior (consumption) and desired emotional state is reminiscent of amygdala functioning.

While this means the amygdalae (and particularly the basolateral nucleus, or BLn) link drug intake to positive reward, it also means they link withdrawal or drug absence to negative emotions. The therapeutic potential of BLn-focused deep brain stimulation (DBS) in moderating these associations (and therefore helping reduce relapse likelihood) is being investigated.

Mood Disorders 

Studies have shown sustained increased amygdala activity in depressed patients, so some researchers have suggested depression is likely the result of outer brain activity imbalance, which also impacts internal structures like the amygdala in a top-down mechanism. However, the opposite is also true for some patients, meaning abnormal activity in the amygdala can lead to imbalances in the outer brain.

Nevertheless, the amygdalae are responsible for assigning value to objects and activities, and their dysfunction could explain a depressed patient’s inability to assign positive value to objects and activities, including themselves. This could lead to lower self-esteem and general life dissatisfaction.

DBS treatment focusing on the amygdala offers potential, but again, more research is required.

Alzheimer’s Disease (AD)

Among the first areas of the brain damaged by Alzheimer’s disease are the hippocampus and its connected structures, including the amygdalae. The amygdalae are known to be affected in AD patients, with their volume and functionality decreasing with age and disease progression.

Effects of this can be seen in early stages of AD and are directly associated with communication disruption between the amygdala and hippocampus. Consequences result from declining cognitive abilities related to making new memories and learning new information, and degradation of emotional processing present in AD patients.

Studies conducted on mice, while not equivalent to human clinical trials, have shown stem cell regeneration in the amygdala, suggesting an avenue for further research that could impact the life course of those with amygdala damage due to AD. 

Urbach-Wiethe Disease (UWD)

Urbach-Wiethe (lipoid proteinosis) is an extremely rare syndrome characterized by hoarse voice since birth and collagen deposits in the skin and soft tissues. More than half of UWD patients have amygdaloid region damage caused by selective calcification of the neurons, leading to lesions.

UWD is also associated with an inability to recognize fear in the facial expressions of others and to experience fear as evidenced in the novel case of patient who lost both amygdalae to the disease.

There is currently no cure for this condition, and treatment is based on signs and symptoms since they vary widely between individuals.

Klüver-Bucy (KB) Syndrome

KB is caused by trauma to the brain, viral brain infections like herpes simplex encephalitis, or other degenerative diseases like Alzheimer’s. People with this very rare neurological syndrome experience memory loss, oral fixation, extreme sexual behavior, and overall peculiar behavior.

Such drastic changes are the result of amygdala lesions damaging both temporal lobes of the brain. These lesions are said to be the cause behind a KB patient’s abnormal emotional responses, including unjustified aggressiveness, fearlessness, and apathy, all of which are associated with amygdala dysfunction.