The Enigma Surrounding the Brain’s Amygdala
By studying the amygdala’s function in both human and animal brains, we can better understand drug treatment and addition.
By Brian A. McCool, PhD
Academy Contributor
About 180 years ago, not long after the New York Academy of Sciences was founded as the Lyceum of Natural History in New York City, the amygdala, those almond-shaped structures within the basal ganglia of the brain, initially was described as discrete anatomical entities deep in each of the temporal lobes. But the behaviors governed by the left and right amygdala have remained subject to interpretation ever since.
While it is generally accepted that the amygdala is somehow responsible for regulating emotions, diverse experimental systems and approaches have until now prevented a unified appreciation
of its function. To contribute to the on-going, evolutionary process that is shaping our understanding of this important brain region, 205 basic and clinical scientists recently attended an important conference on the subject in Galveston, Texas.
Ultimately, it was agreed that the amygdala generally appears to be an arbitrary collection of some 20 different cell groups that can be divided into at least four behaviorally functional units. Together, these units determine how the brain integrates sensory and cognitive information to interpret the emotional significance of an event or thought. Regulating Human Behaviors Several scientific sessions focused on the behaviors regulated by the human amygdala. A number of the sessions highlighted the amygdala’s role in the emotionally motivated assessment of environment and memory.
Using patients with amygdala damage, the University of Iowa’s Ralph Aldophs, PhD, described studies indicating that this brain region is active when individuals make socially-relevant subjective judgments, in this case related to the interpretation of facial expressions associated with negative emotions. Importantly, the interpretation or expression of declarative “facts” regarding negative emotion appears intact in these individuals.
The Amygdala’s Role in Cognitive Processing
Using PET scans, Raymond Dolan, MD, Institute of Neurology in London, U.K., found that this subjective interpretation of negative facial expressions by normal individuals did not require cognitive recognition of the face. Together, these findings suggest that the amygdala’s role in the cognitive process relating to these judgments could occur independent of attention or awareness.
A number of presentations focused on the potential role of the amygdala in human behavioral and neuropathologic disorders. For example, Scott Rauch, MD, PhD, Massachusetts General Hospital, Wayne Drevets, MD, National Institute of Mental Health, and Michael Trimble, MD, Institute for Neurology, London, U.K., reported that amygdala activity or anatomy is altered in a number of different psychological/neurological disorders. A presentation by Anna Rose Childress, PhD, VA Addiction Treatment Research Center, University of Pennsylvania, clearly illustrated this point. Childress presented data indicating that experimentally induced drug craving in recovering cocaine addicts was associated with increased activity in both right and left amygdala and in anterior cingulate cortex.
Importantly, preliminary studies with both drug-based and behavioral interventions, treatments, that attenuate self-reported desire for cocaine, appear to inhibit amygdala activation during these craving states. However, in contrast to pharmacologic treatment, behavioral modification therapy increased brain activity in the orbito-frontal cortex, suggesting that the relative levels of activity between the “emotional” amygdala and the “cognitive” cortex may be an important determinant in the process leading to both drug addiction and recovery.
Animal Models of Behavior
Extensive studies of the amygdala in several mammalian species have provided substantial insight into animal correlates of human amygdala function. This is especially true of the non-human primate studies presented by David Amaral, PhD, University of California, Davis.
In these studies, experimental bilateral lesions in the amygdala of adult nonhuman primates demonstrate that this brain region is intimately involved with the subjective evaluation of novel environmental or social stimuli. Specifically, animals with lesions were less reluctant than normal controls to approach and interact with novel objects, and were more “uninhibited” during social interactions with unknown monkeys.
While these results clearly compliment findings in humans with amygdala damage, Amaral reported that, in contrast to adults, bilateral lesions in infant monkeys did not affect responsiveness to novel objects, and did cause more reluctance to participate in social interactions. These latter findings emphasize our lack of understanding regarding the long-term influence of social and physical development on amygdala function and underscore the need for additional investigations in non-human primates.
A number of reports focused on the behavioral role of the amygdala in rodents. Historically, studies using this animal system have provided the impetus for most of the human studies described above. In addition, current findings are beginning to provide a detailed understanding of the wealth of neurochemical and cellular mechanisms that appear to influence amygdala-dependent emotional learning in rats and, presumably, humans.
For example, Jim McGaugh, PhD, Center for the Neurobiology of Learning & Memory, University of California Irvine, presented an overview of his work in rats. It implicates specific neurotransmitter systems, namely those for norepinephrine and acetylcholine, as chemical mediators regulating amygdala activity related to emotional and stress-influenced memory formation.
Cellular & Molecular Insights into Amygdala Function
Similarly, Michael Davis, PhD, Emory University, presented recent findings indicating that amygdala glutamate receptors, specifically the N-methyl-D-aspartate isoform, are intimately involved with the ability of rats to extinguish fear-associated memories (also known as “extinction”). Importantly, manipulations of this particular membrane protein can enhance extinction, suggesting that this receptor may be an attractive target for therapies designed to resolve memories that elicit pathologic fear, as in posttraumatic stress disorder. Together, these findings emphasize the complexity and apparent wealth of neurochemical mechanisms that govern neuronal activity in the amygdala.
The most obvious advantage that animal models provide over studies in humans or in non-human primates is the relative ease with which basic biologic processes may be directly investigated. Denis Parj, PhD, Rutgers, State University of New Jersey, described the unique properties of a particular amygdala subdivision, the intercalated cell bodies. He concluded that this subdivision might help establish the timing and context of in-flowing sensory information, potentially representing a physiological mechanism that would help distinguish a “fearful” event from an innocuous one.
Similarly, Hans-Christian Pape, Ph.D., Otto-von-Geuricke University, Magdeburg, Germany, presented data indicating that amygdala neurons have intrinsic, rhythmic membrane oscillations that may aid in their communications with other brain regions.
Finally, Paul Chapman, PhD, Cardiff University, Cardiff Wales, U.K., provided an overview of our knowledge regarding the long-term alterations in amygdala neurotransmission associated with fear learning. Chapman noted that the mechanisms underlying memory-related, long-term amygdala adaptations appear to be distinct from those involved in other brain regions.
These findings emphasize that we are just beginning to appreciate the fundamental physiology regulating the amygdala’s involvement with “emotional learning.”
Also read: Teaming up to Advance Brain Research
About the Author
Brian A. McCool, PhD, is an assistant professor in the Department of Medical Pharmacology & Toxicology at the Texas A&M University System Health Science Center in College Station, Texas
