By: Clara O’Hara
What is the amygdala?
The amygdala is a small part of the limbic system of the brain, specifically on the lower part of the brain below the hypothalamus, responsible for body function, and in front of the hippocampus, responsible for memory.
What does the amygdala do?
The amygdala, within the limbic system, is responsible for emotions, primarily fear, as well as emotions related to stimuli that the brain finds repulsive and stimuli that are satisfying. Responsibility in emotions consists of behavior, impulse, and learning, such as decision-making, attention, and memory. The amygdala shows responsibility for emotions by learning the emotion and choosing how the amygdala responds to the emotion over time. As the amygdala responds to emotion over time, in connection with other parts of the limbic system, the hypothalamus and hippocampus, the amygdala can lose the emotion over time and may become a different emotion. The amygdala shows responsibility for emotions by connecting emotion to a memory. These include positive or negative emotions. Sensory information is influenced by the amygdala in the case of a simultaneous occurrence of previously learned behaviors and new or not-learned behaviors.
What happens when the amygdala is damaged?
The dysfunction of the amygdala has been responsible for many psychiatric disorders, like anxiety, depression, and PTSD. The cause of the dysfunction contributing to psychiatric disorders is the dysfunction of neural activity. Examining neural activity in the amygdala of people with psychiatric disorders, a reduction had been found in trying to elicit responses and neural feedback, compared to people without psychiatric disorders, who showed no reduction. It was presented in the left and right areas of the amygdala.
This would mean that in responding to someone purposefully causing someone with anxiety, schizophrenia, or PTSD to react, the person would not be responsive, both in reacting and in the activity of the amygdala. The response, however, would be different in someone without a psychiatric disorder, where they may be more responsive to someone purposefully causing someone to react. Having no effect on eliciting responses, however, excessive levels of neural feedback were found.
This is dangerous for someone with amygdala dysfunction, as they cannot respond appropriately to a purposeful threat or attack from someone. Additionally, amygdala dysfunction can cause inappropriate attribution and alertness of emotions.
In studies examining concussion of the amygdala in animal portrayals of the human brain, damage to the amygdala causes increased levels of fear compared to subjects without injury. In considering the context of the situations, the subjects seemed to feel fear in abnormally fearful situations, whether conditioned or new.
Patients, particularly in older patients, with damages to their amygdala may contribute to causing Alzheimer’s disease and other neurodegenerative diseases. Specifically, in amygdala atrophy, lewy bodies of misfolded proteins develop. High or little accumulation of these misfolded proteins in the amygdala can affect and determine the severity of the impact of the neurodegenerative disease.
Treatment options
Psychiatric treatment, which may include medication or therapy, is often helpful in treating the dysfunction of the amygdala. Cognitive therapy and imipramine, specifically, have been proven effective in treating resulting conditions of dysfunction of the amygdala.
In treating psychiatric conditions, imipramine increases expression of kinases, enzymes that catalyze the transfer of a phosphate group from ATP to a specific molecule through high energy, ERK, pERK, or both in brain areas such as the hippocampus, cortex, amygdala, and striatum
In treating Alzheimer’s disease, imipramine reduced the protein-binding creation of Alzheimer’s disease (AD). Johnson et. al. examined the positive effects of imipramine and olanzapine in reducing Alzheimer’s disease. Analyzed in a highly-throughput screener, a method for drug discovery, eight blood-brain barrier-permeable hit compounds were found to reduce the apoE4-catalyzed Aβ oligomer, a protein predictor of Alzheimer’s disease, and fibril formation in a dose-dependent manner. Five compounds were non-toxic toward clustered neurons and also reduced apoE4-promoted Aβ and tau, proteins also involved in determining Alzheimer’s disease in the amygdala and neuropathology in a dose-dependent manner. Three were determined to be inhibitors of apoE4. The two inhibitors, a means of biologically preventing the protein, of apoE4 significantly marked showing improvements in cognition and clinical diagnosis among apoE4-catalyzed Aβ oligomers – imipramine and olanzapine.
Laser interstitial thermal therapy (LITT) is a surgical technique that has shown some effectiveness in treating damages to the amygdala; however, research has also shown relapse or causal development of damages. The use of MRI-guided laser interstitial thermal therapy for amygdala ablation involves the laser removal of part of the amygdala, either unilaterally or bilaterally. There have been some cases of amygdala ablation showing effectiveness of amygdala cases of up to a year, with PTSD patients experiencing no symptoms. However, some patients who had sought amygdala ablation for PTSD relapsed, with symptoms showing after two weeks, one month, or two years. Research also shows the possible application of LITT in the treatment of Alzheimer’s disease, specifically in drug delivery. The effectiveness of blood-brain cell membrane permeability, which serves as a cause of Alzheimer’s disease, with decreased effectiveness in permeability, increases when placed under LITT and drug deliveries.
Conclusion
The amygdala is a part of the brain that is responsible for emotional regulation, such as fear. Dysfunction of the amygdala can lead to a lack of response to stimuli and, further, psychological disorders. It can also lead to Alzheimer’s disease and other dementia-related diseases. To treat dysfunctions in the amygdala, psychiatric treatment, specifically imipramine and cognitive therapy, has been proven to be helpful. Laser interstitial thermal therapy has been significant in therapies treating dysfunctions of the amygdala, such as amygdala ablation for PTSD and Alzheimer’s disease.
Resources
Blier, P., et al. “Role of 5-HT1A and 5-HT2C Receptors of the Dorsal Periaqueductal Gray in the Anxiety- and Panic-Modulating Effects of Antidepressants in Rats.” Behavioural Brain Research, Elsevier, 8 Feb. 2021, www.sciencedirect.com/science/article/pii/S0166432821000462?casa_token=ZBGficZYG9EAAAAA%3AwRkR1T57vRH9UjnLEx5j8tBoeYtnBZs4mUyPTiOy1oCUDJygJl621EQLRPhxEf9oJL4f5F9CClU.
Johnson, Noah R., et al. “Imipramine and Olanzapine Block APOE4-Catalyzed Polymerization of AΒ and Show Evidence of Improving Alzheimer’s Disease Cognition – Alzheimer’s Research & Therapy.” SpringerLink, BioMed Central, 29 June 2022, link.springer.com/article/10.1186/s13195-022-01020-9.
