How does Sound & Emotion Connect in Memory?

An interview with Dr. Joseph E. LeDoux and my hope for the application of more basic neuroscience to Misophonia

Why is sound so powerful? This is a question people with misophonia are likely to think about all the time. What is the connection between sound and emotion? Most important, why does sound and emotion connect in our memories and how does this apply to treatment models? A few years ago I interviewed Dr. Joseph E. LeDoux (neuroscientist, author and musician) about this subject and I think it is time to share this again!

While Dr. LeDoux has retired from active research (but is still writing incredible books & making his music), it is my hope that other neuroscientists follow his work and apply this kind of exploration to misophonia. I believe this interview is very much worth revisiting since we have recently seen a significant increase in misophonia studies, but perhaps not in the important direction Dr. LeDoux discusses here.

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: Would you tell us a little about the next part of the study?

Joe: We hypothesize that neural responses in different parts of the amygdala predict different reasons for auditory and other kinds of sensory stimuli to elicit exaggerated responses. As previously mentioned above, the lateral nucleus is the sensory input region of the amygdala and the central nucleus is the behavioral output region. An individual might respond more to a stimulus because her lateral amygdala is overly sensitive to the threat value of the stimulus, or because her central amygdala is overly reactive.

JENNIFER: How will this help people with difficulties related to over-responding to auditory information?

Joe: The new knowledge that we will obtain will shed light on how neural mechanisms in the amygdala contribute to auditory over-responsivity.

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 outputs 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? 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 a 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 hyperactivity.

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

In my view, this research holds up as highly promising, specifically to the understanding of misophonia. First, the research suggests that the repetition of stimuli is highly important. While we know that repetition is a factor in misophonia sounds (and in misokinesia) we don’t know why. More emphasis on the ‘why’ in research will lead us to better interventions.

Second, while we do not think misophonia is caused by a particular trauma, we do know that the experience of misophonia acts like trauma in terms of memory. Why not explore these processes more? Similarly, wouldn’t it be prudent to explore if auditory gating (ability to filter out sounds) and general over-responsivity to sounds (as suggested by the super-responders in this study) were risk factors in regard to developing misophonia? Does being a super-responder or having difficulty filtering different sounds in the environment make treatment via learning models more difficult for some? Does this suggest that we need to reach beyond traditional learning models?

It is my hope that concepts from basic neuroscience that are already being studied (and that have been for a very long time) be applied to misophonia research. This is on my mind today, has been for decades and I am sure will continue to be.