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Abnormal Brain Networks Underlie Misophonia



THE INTERACTION IN THE ANTERIOR INSULA CORTEX (AIC) was driven by greater activation in misophonic subjects compared to control subjects in response to trigger sounds (A). Significant activation differences between misophonic and control subjects did not occur to unpleasant or neutral sounds (B). Activity in both the left and right AIC varied linearly with the subjective rating of misophonic distress in the misophonic group, as shown in confirmatory plots (C).

Functional and structural brain imaging illustrate the neurologic basis for misophonia, a little known condition which is often mistakenly diagnosed as tinnitus.

Misophonia—literally, “hatred of sound”— may be the most common disorder you've never heard of. Those who have it experience extreme anger or anxiety upon hearing certain highly specific sounds, such as a spouse chewing or an office mate's keyboard clicking. “These individuals are normal in every other respect,” according to Timothy Griffiths, DM, “except that they can't sit down to eat with their family,” or work in the same room as someone else.

While the condition has been known for almost two decades, its neurological basis has been unclear. Now, Dr. Griffiths, Wellcome senior clinical fellow and professor of cognitive neurology at Newcastle University in the United Kingdom, and colleagues have elucidated the functional and structural differences in the brain that underlie misophonia. They have shown that misophonic reactions are accompanied by highly exaggerated responses in the anterior insula cortex (AIC), a region of the brain critical for emotional processing, and in other regions associated with regulating emotional responses.

They further showed that the sympathetic responses that are part of the misophonic reaction were mediated by AIC activity, and that misophonic subjects had an elevated level of myelination in a prefrontal region that communicates with the AIC.


DR. TIMOTHY GRIFFITHS: “I was very skeptical about this as a neurological condition before I talked with people who had it. But now, it is clear this is a distinct syndrome,” and one that doesn't overlap with any other diagnoses, such as obsessive compulsive disorder.

Misophonia is very different from mild irritation, Dr. Griffiths said, and also different from the reaction most people have to hearing nails scraped on a chalkboard; misophonic triggers are noises most people are easily able to ignore.

“I was very skeptical about this as a neurological condition before I talked with people who had it,” he said. “But now, it is clear this is a distinct syndrome,” and one that doesn't overlap with any other diagnoses, such as obsessive compulsive disorder.


To better understand its physical basis, Dr. Griffiths, along with first author Sukhbinder Kumar, PhD, and colleagues, acquired functional and structural MRI data in 20 subjects with misophonia and 22 age- and sex-matched controls. In the scanner, individuals were tested for changes in brain blood flow for a variety of sounds, including chewing, the most common trigger sound for the misophonic subjects; sounds generally perceived as unpleasant, such as a baby crying or a person screaming; and neutral sounds, such as rainfall. Subjects rated the unpleasantness of the sound and, for misophonic subjects, its ability to trigger a misophonic reaction. Heart rate and galvanic skin responses were also tested.

When presented with trigger sounds, misophonic subjects had highly specific increases in activity in the AIC, which was not seen in controls, and the degree of AIC activity in misophonic subjects was tightly correlated with their rating of the sound as a misophonic trigger. The increase in AIC activity was much greater than the increase in response to the generally unpleasant sounds, which was very similar to controls.

“We are not looking at a heightened sensitivity to unpleasant sounds in general here,” Dr. Griffiths said. “It is a very specific phenomenon.”

Dr. Griffiths also found that in people with misophonia, higher activity in the AIC was correlated with higher activity in other brain regions, especially the medial frontal cortex and posterior medial cortex, both of which have been associated with emotional processing, as well as the hippocampus and amygdala. Both galvanic skin response and heart rate increased specifically in response to misophonic triggers.

The change in the relationship between AIC and medial frontal cortex “is not just a quantitative change, it is a qualitative change,” Dr. Griffiths added. Normally, when medial frontal activity goes up, AIC activity goes down, not up as it does in misophonia, suggesting a control mechanism to suppress emotional reactions which may be lacking in misophonia.

Finally, the team showed that the same frontal regions involved in the misophonic reaction were also significantly more myelinated than in controls. “This raises the question whether the structural abnormality is primary, or whether it develops as a function of the abnormal network activity,” Dr. Griffiths said. “We don't know.”


“This paper provides compelling evidence for changes in the brain that could account for misophonia,” said Vilayanur Ramachandran, PhD, director of the Center for Brain and Cognition and professor of psychology at the University of California, San Diego, who was not associated with the study.

“This study's combination of functional and structural imaging, along with sympathetic testing, provides compelling evidence to confirm misophonia as a syndrome. It is a major step forward,” said Dr. Ramachandran, whose work has also explored the physical basis of misophonia. The findings will likely help in the search for treatments, which are much needed, he said. “The impact on lifestyle for misophonic patients is almost as severe as for obsessive compulsive disorder. It is truly horrible for them.”

Misophonia results from the creation of an inappropriate classical conditioned reflex, said Pawel Jastreboff, PhD, DSc, professor emeritus of otolaryngology — head and neck surgery at Emory University School of Medicine in Atlanta. In 1999, together with his wife, Margaret Jastreboff, PhD, he recognized that a group of patients he was seeing for hyperacusis did not fit the standard criteria of intolerance for all types of loud sounds. That led the two to offer the first description of misophonia.

In his work with over 1,000 misophonia patients, he commonly encountered those who could link the onset of their condition — often, but not always, in late childhood or adolescence — to exposure to the offending sound in a situation involving a strong negative emotional status, frequently in a context they could not escape, such as a family mealtime with a relative whose chewing repelled them.

Typically, but not always, the trigger spread beyond the initial stimulus, to encompass chewing by others, for instance. “The plastic changes occurring in the brain due to this situation can cause the reaction to grow stronger and detection of the trigger to become more acute,” he said.

Extinguishing the reflex is the goal of treatment. At Dr. Jastreboff's clinic, along with counseling to help the patient understand their condition, treatment includes pairing the trigger sound with pleasant sounds, such as music, to create a more positive association with this new, complex stimulus, he said, with the volume of the pleasant sound decreased gradually over a period of months.

Dr. Jastreboff praised the imaging study, but suggested it would be wrong to interpret the functional and structural changes seen in the study to mean that treatment is futile. “Effective treatment is possible for many patients,” he said.

While there are few studies on the condition's prevalence, Dr. Jastreboff thinks it is far more common than recognized. He estimates that more than half of tinnitus patients who seek treatment experience some degree of misophonia, perhaps due to shared brain networks underlying both conditions. “It is crucial to be on the alert for misophonia in tinnitus patients,” he said. “If you are treating only tinnitus and ignoring coexisting misophonia, there is a high chance you will fail in tinnitus treatment.”


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