A new study published in Hearing Research has questioned one of the leading hypotheses about the biological basis of misophonia and hyperacusis—showing that decreased sound tolerance may not be driven by abnormal levels of brain excitatory or inhibitory neurotransmitters.
Researchers from the University of Sussex and Leiden University used magnetic resonance spectroscopy (MRS) to measure concentrations of glutamate (an excitatory neurotransmitter) and GABA (an inhibitory neurotransmitter) in the auditory cortex, insula, and a control region in the visual cortex. The goal was to test whether individuals with misophonia or hyperacusis show an altered balance between excitation and inhibition—a proposed marker of cortical “overactivity” in sound intolerance.
Using an advanced MEGA-PRESS MRS sequence to optimise GABA detection, the team compared neurotransmitter levels across groups while excluding participants with tinnitus, migraine, or autism to ensure diagnostic clarity.
Key findings
The results revealed no significant differences in glutamate or GABA levels between participants with misophonia, hyperacusis, and healthy controls. Bayesian statistical analyses supported these as sensitive null findings, meaning the data provide strong evidence against large or moderate neurochemical differences.
These results challenge the assumption that decreased sound tolerance is primarily a neurochemically driven disorder of cortical excitation or inhibition. Instead, they suggest that the mechanisms underlying misophonia and hyperacusis may arise from network-level or functional dysregulation—for example, in connectivity, attention, or emotional reactivity—rather than basic chemical imbalance in the auditory cortex.
Why this matters
This study is a significant step toward refining the neurobiological model of sound intolerance. It highlights the need to look beyond neurotransmitter levels to understand how auditory, emotional, and cognitive systems interact in misophonia and hyperacusis.
At Hashir International Institute and The Hearing Well Practice, these findings reinforce a multifactorial approach: combining accurate audiological assessment with Cognitive Behavioural Therapy (CBT) and emotion regulation strategies that address the brain’s interpretive and attentional responses to sound, not just its chemical substrates.
As research continues, integrating neurochemical, neuroimaging, and psychological data will help shape a more complete understanding of how the brain processes unwanted sound—and how best to help patients manage it.
Full citation
Ward, J., Agbude, R., Smees, R., Simner, J., & Ronen, I. (2025). The neurochemistry of decreased sound tolerance: A magnetic resonance spectroscopy (MRS) study of misophonia and hyperacusis. Hearing Research, 468:109440. https://doi.org/10.1016/j.heares.2025.109440
