Auditory Reactivity & the Amygdala: Misophonia Connections

An Interview with Joseph E. LeDoux, PhD

Posted Sep 14, 2016

bykst @ pixabay used with permission
Source: bykst @ pixabay used with permission

Jennifer: Joe, can you explain the difference of conscious and non-conscious learning?

Joe: Imagine two cars in the highway with several people in each of them. Both cars are tuned to the same radio station. A Hard Day’s Night is playing when an unexpected patch of ice causes a crash between the two cars. Although no one is seriously injured, they all experienced some pain and discomfort. Later on, the song will trigger the same body reactions, such as increased heart rate or sweat, and also remind them of the accident.  But these are separate memories of the brain. One is implicit (non conscious) and the other explicit (conscious).

Jennifer: So the memory of the pain and discomfort of the crash occurs without any conscious awareness and can in fact include physiologic responses, such as increased heart rate, sweating, etc. of which we are not in voluntary control?

Joe: Yes, that’s right.

Jennifer: How do you do this in your lab?

Joe: To achieve a deep understanding of the brain mechanisms that go on in real life situations, such as the car crash, scientists have to design experiments that are simplified versions of the real-life situation. In order to simulate non-conscious or implicit learning we utilize Pavlovian or classical conditioning to see how our rodent subjects make associations between previously neutral and negative stimuli. With this approach we have been able to determine that two different regions of the amygdala, its Lateral and Central nuclei, are necessary for this kind of learning. The brain pathways that carry the information (for the neutral and aversive stimuli) converge in the lateral amygdala. It then communicates with the central amygdala, which for its part, sends information to lower brain areas that control the body reactions mentioned above. As a result of learning, the neutral stimulus can flow more easily through the circuit to elicit the responses. We assess this by measuring neural activity in these areas before and after learning.  And what we find is that amygdala neurons are more active after learning—more activity in the lateral amygdala means that the central amygdala will also be more active, and so will it outputs.  The net result is a bigger behavioral response.

Jennifer: But what happens if some people, or rodents, are more vulnerable to respond to stimuli with greater reactivity in the first place?

Joe: We know that in any such situation of danger, different people respond differently. Some respond strongly and other weakly, and still others are in the middle.  Many scientific studies focus on the middle or average response.  This was useful in identifying which areas of the amygdala are important, but ignores the fact that rats, and people, respond differently.

Jennifer: So, are you saying that most of the work that is done on learning and conditioning does not consider these possibly constitutional, or inborn, differences in reactivity?

Joe: Yes.But to make up for this neglect we have thus begun study rats that respond strongly and weakly to the neutral stimuli. We use these to then explore the hypothesis that neural responses in the amygdala are predictive of strong and weak behavioral responses to threats.  Our initial studies confirm this and allow us to proceed to our main object.

Jennifer: I would imagine this will help with an understanding of how conditioning of implicit memories are learned and studied, and may have implications for people who suffer with disorders in which auditory over-responsivity is an issue.

Joe: Yes, this work could lead to new ways to diagnose and treat auditory over-responsivity.  If we simply use the behavioral output we may miss the fact that some people are over sensitive and others overreactive due to wiring.  If this is the case, it makes sense that they would need different treatments.

Jennifer: Do you think the study will also add to knowledge about the specific type of auditory stimuli that might be aversive to specific people, like with misophonia

used with permission of J.E. LeDoux
Source: used with permission of J.E. LeDoux

For example, you used repetitive auditory stimuli which might have implications in particular disorders in which auditory gating (the process by which irrelevant information is filtered from the higher cortical centers of the brain in order to avoid overloading) is an issue?

Joe:  We have been using repetitive stimuli for while because that’s necessary to get reliable neural responses. But now that we know that stimulus repetition is a factor that is of clinical interest it might be possible to design studies that can directly isolate the contribution of repetition to hypersensitivity and/or hyperreactivity. 

Jennifer: This sounds very promising! Thank you very much for taking the time to do this interview. 

Joseph LeDoux is the Henry and Lucy Moses Professor of Science at NYU in the Center for Neural Science, and he directs the Emotional Brain Institute of NYU and the Nathan Kline Institute. He also a Professor of Psychiatry and Child and Adolescent Psychiatry at NYU Langone Medical School. His work is focused on the brain mechanisms of memory and emotion and he is the author of The Emotional Brain,Synaptic Self, and Anxious. LeDoux has received numerous awards, most recently the 2016 William James Book Award from the American Psychological Association. LeDoux is a Fellow of numerous Scientific Academies and Institutes and is also the lead singer and songwriter in the rock band, The Amygdaloids.

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Reprinted with permission of Misophonia International Magazine