Report on Findings of the LeDoux Lab by Jennifer Jo Brout

Joseph E. LeDoux

One of the working theories related to mechanisms underlying misophonia is that auditory stimuli may be misinterpreted by the brain as dangerous, or threatening. As such, the brain responds as it would if it were actually in danger. When we are in danger, our  freeze/fight/flight system[i] is set off. When this happens, our autonomic (involuntary nervous system) is activated, or aroused.

When our involuntary nervous system is aroused physiological and other hormonal changes occur (e.g. blood is redistributed throughout our bodies, the heart rate raises, etc. ) to enable us to “flee” from the apparent danger or “fight” if we must.

This is a system that all mammals have that has been conserved by evolution.[ii]  The feelings we have as a result of the fight/flight system being activated are associated with “wanting to get away from the offending stimuli (sound, or visual), or irritation, anger or rage. In other words, the irritation, anger and rage that we feel when faced with sounds that are noxious likely manifest from the physiologic fight/flight response. It is difficult to separate our physiological feelings from our emotions, which is why looking at the areas of the brain that react to sound and other stimuli is important.

The fight/flight response is mediated by a part of the brain called the amygdala. At the LeDoux lab at NYU Joseph LeDoux and his colleagues have been studying the amygdala for decades. They have done groundbreaking work in this part of the brain that mediates fight/flight, and is also involved in neural processes related to memory related to fear.

The amygdala is also involved with memory. In terms of misophonia, regardless of whether or not one is born with the disorder individuals make memories in which the body’s fight/flight response is associated with particular sounds. In addition, some of us may be born with a higher arousal system, or may simply be more sensitive to auditory stimuli. Therefore, some of us may be more vulnerable to forming these memories.

Once these memories are formed, they are similar to trauma memories (yet they are not like trauma memories as there is no associated traumatic event). However, prior research suggests that auditory stimuli (or misophonic sounds) will automatically activate the autonomic nervous system and fight/flight, leaving people with misophonia feeling angry or trapped by sounds or other stimuli for no apparent reason.

In an  analysis of the auditory stimuli that are most noxious to people with misophonia, I noted that repetitious stimuli is a common characteristic.

Normally, in order to test how these memory associations are made, the rodent sample used is tested in a typical learning paradigm. That is, the rodent is “taught” to associate a sound with an unpleasant stimulus. Then the situation is reversed, and the rodent eventually unlearns this response (or extinguishes).

Dr. LeDoux has been working on the ability to reverse these associated memories for many years. He has done so in the realm of “basic science”. Basic neuroscience strives to look at specific brain processes that may then inform typical and atypical populations and therefore numerous disorders.

Because typical exposure therapy and therapies that have relied upon re-associating stimuli with events or other stimuli generally do not show results that are long lasting for disorders such as PTSD, or even phobias, LeDoux has looked for other ways in the brain to change the association between the automatically activated threat response once it has been associated with a particular stimuli. This is a process called memory re-consolidation.

Believe it or not, each time we retrieve a memory from our long term memory system it alters slightly. This is something LeDoux’s lab discovered early in the millennium .This is contrary to prior ideas about memory in which scientists thought that once a memory was formed it was stable and always retrieved as the exact same memory.

Using memory reconsolidating LeDoux and colleagues have already proven that the automatic physiological response to a stimuli (or a memory in regard to sound in misophonia) can be changed in simple ways. Whereas most behavior therapists rely on exposure to aversive stimuli in order to desensitize people to trauma  (in this case a noise, pattern of sound, or repeating noise) or to relearn an association between a sound and a particular person, etc. they are often unable to obtain results, and if they do obtain results, they don’t last. This is because of memory.

However, in LeDoux’s lab this problem with memory was solved many years ago using subconscious ways to change the way memory was reconsolidated. I believe, and have since I first learned of this work, that this is a therapy that is most promising for misophonia.

In our study at NYU at the LeDoux Lab, Dr. LeDoux and Dr. Lorenzo Díaz-Mataix

are studying two parts of the amygdala in order to see where the problem may arise in regard to auditory over-responsivity, or misophonia.

The lateral amygdala is the part of the brain structure where the auditory (or other sensory information) comes in and the central amygdala is the part where signals are sent that send the message “go or no go” for fight flight. One of the roles of central amygdala is to mediate valence (positive or negative assignment) to sensory information.

Although the brain works in an interconnected and highly complicated manner, and there are other candidate brain regions for misophonia. Since, we know that autonomic (involuntary) nervous system arousal is involved in the disorder, we know that the amygdala is certainly a region we should be looking at.

In this study Dr. Díaz-Mataix  separated out rodents by the level of their over-responsivity to repetitive stimuli. They rodents naturally fell into groups of extreme high responders, high responders, typical responders and low-responders. That means, that even in rodents there seems to be a range from extreme sensitivity to low sensitivity to repetitive auditory stimuli (just as there seems to be with people). People with misophonia would be like the extreme over-responder rodents.

Results show that extreme-responders are least likely to “un-learn” the association between  noxious stimuli and the physiological response (or fight/flight). However, this is a scientific experiment helps supports:

• This the misophonia symptoms are truly due to physiological phenomena (i.e. if you can see it rodents who don’t “think” as we do, then we have more evidence that this is not a “psychological problem”
• If “extreme-responders” are similar to those of us with  misophonia and are unable to “unlearn” an associated response between stimuli and an event ,than simple exposure therapy is highly unlikely to work
• Given this information, memory reconsolidation, which is working for people with phobias in new trials, may be a promising remediation for misophonia symptoms

The illustration below is a poster from a neuroscience conference that demonstrates the first part of our study.  The IMRN hopes to continue  to support this work if more funding becomes available. We would very much like to see memory reconsolidation therapy for misophonia trialed.

[i] The physiologic response we often refer to as fight/flight follows a particular sequence that includes freezing (which comes first). However, we often freeze so quickly that it is unnoticeable to the human eye and/or we are not conscious of our self in this modality.

[ii] LeDoux (2015) Anxious: Using the Brain to Understand and Treat Fear and Anxiety. Penguin Random House. New York.