Is the iron dysregulated in the mirror neuron system in misophonia?

In my latest paper, we hypothesize that in Misophonia (a condition characterized by intense emotional and physiological reactions to specific human-generated sounds) there is a self-perpetuating cycle of mirror system hyperactivity mediated by iron dysregulation.

Here is the predicted pathological self-perpetuating cycle: Mirror system hyperactivity  →  Metabolic stress  →  Iron accumulation  →  Inflammation  →  Impaired inhibition  →  Involuntary mimicry.

We suggest that therapies aimed at breaking this self-perpetuating loop may offer effective strategies for managing Misophonia.

Reference:

[1] Pradeep Dheerendra, Soumita Ramesh, "Is iron dysregulation in the mirror motor cortex associated with misophonia?", Medical Hypotheses, vol. 204, p. 111765, Nov 2025.

https://doi.org/10.1016/j.mehy.2025.111765

Abstract: Iron homeostasis plays a critical role in brain function and mental health, yet its dysregulation in specific psychiatric conditions remains underexplored. In this article, we propose iron accumulation in the brains of individuals with misophonia — a condition characterized by intense emotional and physiological reactions to specific human-generated sounds. Based on the known involvement of the mirror neuron system in misophonia, we hypothesize that excessive iron concentration in the mirror motor cortex is a result of abnormal hyperactivity in this region. We propose that chronic overactivation of mirror motor cortex leads to increased metabolic demand and elevated cerebral blood flow, facilitating excessive iron influx. This may trigger low-grade chronic neuroinflammation, promoting maladaptive synaptic plasticity and long-term potentiation. The resulting impaired inhibitory control and heightened functional connectivity with primary sensory areas may further exacerbate hyper-mirroring. We propose future studies should confirm the existence of this self-perpetuating cycle which would imply that interventions aimed at reducing mirror system hyperactivity could disrupt this cycle and offer a promising therapeutic strategy for misophonia.

Here is a copy of the full paper:

https://drive.google.com/file/d/1ffMrfowWitjrrObcEvZ_67UN64tZNNMx/view?usp=sharing