Amygdala Insula Retraining (AIR) in the Management of Mold Illness Symptoms

More than a substantial proportion of individuals in the United States with a history of chronic exposure to water-damaged buildings and indoor mold report persistent, disabling symptoms that extend well beyond the period of initial exposure. This condition is often described as mold-related illness or biotoxin-associated illness. Symptoms commonly include fatigue, post-exertional malaise (PEM), cognitive dysfunction, autonomic and cardiovascular disturbances, respiratory and sinus symptoms, gastrointestinal dysregulation, dermatologic manifestations, and heightened sensory sensitivity. These symptoms are heterogeneous, frequently involve multiple organ systems, and overlap in extent and severity with other neuro-immune conditions such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Mold-related illness, similar to ME/CFS, is likely to pose a significant burden on both healthcare systems and patient quality of life. Despite growing clinical recognition, substantial gaps remain in understanding individual susceptibility, pathophysiology, and optimal treatment approaches. Current hypotheses suggest that immune dysregulation, neuroinflammation, autonomic nervous system imbalance, and persistent stress-response activation may play central roles in symptom perpetuation. Pharmacologic and detoxification-based interventions are often heterogeneous in response, and the development or validation of targeted treatments remains limited.

Emerging evidence increasingly supports the role of the mind-body connection in modulating autonomic, central, and peripheral nervous system activity, immune function, and gastrointestinal regulation. Holistic strategies such as mindfulness, meditation, and amygdala and insula retraining (AIR) have demonstrated objective, measurable effects on heart rate variability, fatigue, pain, mood, quality of life, anxiety, depression, and gastrointestinal symptoms across related neuro-immune conditions. Proposed mechanisms include vagus nerve activation, autonomic nervous system rebalancing, stress reduction, and downstream immune modulation.

AIR is based on the principle that environmental insults, including mold and biotoxin exposure, can sensitize threat-processing centers of the brain such as the amygdala, resulting in persistent hypervigilance and maladaptive neuroendocrine and immune signaling. This state may perpetuate neuroinflammation, dysautonomia, and symptom chronicity even after removal from exposure. AIR aims to de-sensitize these neural circuits, interrupting maladaptive feedback loops and reducing excessive hormonal and cytokine release.

Our clinical group has recommended AIR in individuals with mold-related illness and has observed favorable anecdotal clinical responses. This intervention is readily accessible, non-invasive, and carries minimal risk. We therefore aim to conduct a pilot study of AIR in individuals with mold-related illness to generate preliminary data to support a larger, federally funded clinical trial. Our specific aims are:

• Identify 150 subjects who have received a positive Mycotoxin test in the last year and experience symptoms of mold illness. Subjects will be randomized to either 1. AIR + standard of care or 2. Standard of care/control. Individuals in this latter arm will be waitlisted to receive the AIR intervention after they complete the study.
• Collect standard questionnaires at baseline, three, and six months to capture symptoms and compare changes over time across the two study arms.
• Collect objective wearable data to explore potential mediating mechanisms such as heart rate variability

Inclusion criteria

• Ages 18-80
• Confirmed mold illness through a positive mold mycotoxin test from October 2023-January 2025 OR who are receiving active treatment for mold illness under the care of an MD or ND.
• Able to speak English
• Able to access internet

Exclusion criteria

• Previous experience with brain retraining programs