- Service of Neurosurgery, Southern Arizona VA Healthcare System, AZ, USA
- Division of Neurosurgery, University of Arizona, Tucson, AZ, USA
Correspondence Address:
Jean-Philippe Langevin
Service of Neurosurgery, Southern Arizona VA Healthcare System, AZ, USA
Division of Neurosurgery, University of Arizona, Tucson, AZ, USA
DOI:10.4103/2152-7806.91609
Copyright: © 2012 Langevin J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Langevin J. The amygdala as a target for behavior surgery. Surg Neurol Int 14-Jan-2012;3:
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Abstract
The amygdala was a popular target during the era of psychosurgery, specifically for the treatment of intractable aggression. This mesiotemporal structure was thought to primarily mediate fear and anger. However, recent evidence suggests that the amygdala is part of a complex network that mediates the formation of a larger repertoire of positive and negative emotions. Dysfunctions within the network or the amygdala itself can lead to various mental illnesses. In those cases, deep brain stimulation (DBS) applied focally may treat the symptoms. This review presents data supporting the potential therapeutic role of DBS of the amygdala in the treatment of anxiety disorders, addiction, and mood disorders. The success of DBS for psychiatric conditions will likely depend on our ability to precisely determine the optimal target for a specific case.
Keywords: Addiction, amygdala, deep brain stimulation, depression, post-traumatic stress disorder
INTRODUCTION
The current treatment of psychiatric illnesses depends largely on the pharmacological agents that correct neurotransmiter imbalances, in combination with psychotherapy that uses the mind to heal the disease. Deep brain stimulation (DBS) is currently under investigation to offer another strategy of treatment for otherwise refractory psychiatric illnesses.[
In this review, we present the amygdala as a component of a larger network. The role of the amygdala is portrayed through some of the disorders where it plays a pivotal role. The central aim of the article is to show the importance of the interconnections within the network. An aberrant network component will manifest into various disorders depending on the “weight” of its specific connections and on the activity of its neighboring components. As such the amygdala can be the source of various mental illnesses when giving more or less weight to certain afferents and efferents.
ANATOMY AND FUNCTION
The amygdala is a nucleus located in the mesiotemporal lobe bilaterally with an approximate volume of 1700 mm3.[
The function of the amygdala is to link sensory inputs with psychological and physiological processes.[
Figure 1
The amygdala and its network. This figure shows selected afferents and efferents of the amygdala. Functional groups are color coded. The amygdala screens stimuli received from high-order sensory cortices (orange pathway). The response of the amygdala to the incoming stimulus is determined by the activity of several modulation pathways. These pathways include a context- and memory-based modulation (green pathway), a top-down modulation (red pathway), and a reward-based modulation (blue pathway). BLn: Basolateral nucleus, CEA: Central nucleus of the amygdala, DM Vagus: Dorsal motor nucleus of the Vagus, Lat. Habenual: Lateral habenula, mPFC: medial prefrontal cortex, Nacc: Nucleus accumbens, PAG: Periacqueductal gray area, Rmtg: Rostromedial tegmental nucleus, VTA: Ventral tegmental area
ROLE OF THE AMYGDALA IN ANXIETY DISORDERS
The critical role of the amygdala in fear conditioning is well established.[
A number of recent discoveries have highlighted the role of the amygdala in the pathophysiology of PTSD. In several studies, PTSD patients were exposed to cues (images or sounds) reminiscent of their trauma and then scanned with functional magnetic resonance imaging (fMRI), positron emission tomography computerized tomography (PET CT), or single-photon emission computerized tomography (SPECT). Using this paradigm, the amygdala of PTSD patients was shown to be “overactive” compared to normal controls.[
Functional neuroimaging studies can rarely establish a causal effect between areas of activity and the underlying condition. However, lesioning studies are more successful in this regard. Koenigs et al.[
Taken together, these results reveal the importance of the amygdala in mediating the symptoms of PTSD. Functional inhibition of the amygdala using DBS may therefore prove successful at treating PTSD. We tested this hypothesis[
The decision to choose the BLn as a target was motivated by the fact that it is thought to be critical in both the acquisition and expression of fear conditioning. In addition, it plays a critical role in the modulation of amygdalary activity. The BLn receives important afferents from the mPFC and the hippocampus [
ROLE OF THE AMYGDALA IN ADDICTION
The rewarding and pleasurable effects of drugs of addiction are thought to arise from the activity of the mesolimbic system whereby the dopaminergic neurons of the ventral tegmental area (VTA) activate the nucleus accumbens (Nacc) through changes in their tonic and phasic activity.[
Relapse is the return to drug consumption after a long period of successful abstinence. Relapse in animal models of addiction occurs as a result of re-exposure to a small dose of the drug, exposure to stress, or exposure to environmental cues of the drug administration. The latter form of relapse can be described as a form of conditioning where an environmental cue is associated with the pleasurable effect of the drug, and later, when presented by itself triggers the seeking behavior associated with the drug. This phenomenon appears to play a significant role in human addiction where reminders of drug consumption (e.g. drug paraphernalia, specific building or room) can trigger relapse. Presentation of the cue, even long after withdrawal has resolved, can activate the circuits involved in the drug effect.[
The BLn is closely linked to the mesolimbic system, making it a potential mediator of the cue-conditioning phenomenon at the basis of relapse [
Frenois et al.[
Substance abuse leads to diffuse changes in the cortical surface and the mesolimbic system. These changes are likely to contribute to persistent drug self-administration behavior in patients suffering from addiction. Nevertheless, the amygdala and, in particular, the BLn appear to play a critical role in certain forms of relapse related to exposure of reminders of drug intake or drug withdrawal. In individuals with intractable and life-threatening substance abuse disorder, BLn DBS could improve the chance of remission by reducing the incidence of relapse.
ROLE OF THE AMYGDALA IN MOOD DISORDER
The importance of the frontal-limbic circuitry in depression has been shown in several studies. Notably, Mayberg et al.[
An analysis of the position of DBS electrodes in those patients confirmed that the optimal location is the subgenual cingulate gyrus (cg25), which has dense connections with the amygdala, Nacc, hypothalamus, and the orbitofrontal cortex.[
Some evidence suggests that the amygdala could act as a primary focus in depression. For instance, several patients suffering from PTSD with symptoms associated with overactivity of the amygdala area often suffer from co-morbid depression. In addition, direct stimulation of the amygdaloid area in humans may lead to dysphoria, anger, fear, and tension.[
EXPERIENCE FROM STEREOTACTIC AMYGDALOTOMY FOR INTRACTABLE AGGRESSION
The main experience using the amygdala as a target in behavior surgery comes from stereotactic amygdalotomy for intractable aggression. The role of the amygdala in mediating aggression or violent behavior has long been recognized. For instance, Kluver and Bucy[
The surgical technique has improved since these reports. Nevertheless, the risks of amygdala DBS include anger, mood disturbances, neuropsychological deterioration, and seizures. Interestingly, very few patients who underwent electrical stimulation at low frequency and high amplitude reported anger.[
CONCLUSION
The fundamental role of the amygdala is to link stimuli or events to a series of physiological and psychological processes. The constellation of these processes translates into a specific emotion within the mind. Whether the emotion is negative or positive depends on the nature of the processes activated by the amygdala. In turn, the decision making of the amygdala is determined by several modulatory inputs including the hippocampus (context modulation), the VTA (motivation, reward motivation), and the PFC (higher-order modulation).
This basic function of the amygdala is recruited to participate in several complex behaviors and human experiences. A dysfunction of the amygdala can therefore manifest in different mental illnesses depending on the relative "weight" of individual connections within the circuit and on the activity of other components of the circuit. DBS of the amygdala and, in particular, of the BLn can likely be utilized for the treatment of some mental illnesses. However, the success of this strategy will depend on our ability to determine pre-operatively the likelihood that the symptoms are caused by amygdalary dysfunction.
Publication of this manuscript has been made possible by an educational grant from
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