Amygdala Insula Retraining in the Management of Multiple Sclerosis Symptoms

Multiple sclerosis (MS) is a chronic, immune-mediated neurological condition characterized by inflammation and neurodegeneration within the central nervous system. Despite advances in disease-modifying therapies, many individuals with MS continue to experience persistent and disabling symptoms, including fatigue, cognitive dysfunction, pain, mood disturbance, autonomic dysregulation, sleep disruption, and reduced quality of life. These symptoms often fluctuate and may persist independent of inflammatory disease activity, underscoring the need for adjunctive, non-pharmacologic interventions that target symptom burden and functional outcomes. This study evaluates two distinct educational interventions designed to support symptom management in individuals with MS: a comprehensive lifestyle education program and a neuroplasticity-based brain retraining program known as Amygdala and Insula Retraining (AIR). Lifestyle-focused interventions targeting stress management, nutrition, sleep, physical activity, and environmental exposures have demonstrated benefits across chronic illness populations and are increasingly recognized as important components of comprehensive MS care. In parallel, growing evidence supports the role of mind-body approaches in modulating autonomic nervous system function, stress, and measurable effects on fatigue, mood, pain, quality of life, and heart rate variability. AIR is based on the principle that chronic illness and inflammatory stressors may sensitize neural circuits involved in threat detection and interoception, particularly the amygdala and insula, leading to persistent hypervigilance and maladaptive autonomic signaling. In MS, this heightened neural reactivity may contribute to symptom amplification such as increased fatigue, dysautonomia, and reduced stress resilience. AIR aims to de-sensitize these neural pathways through structured neuroplasticity-based cognitive and mindfulness practices, with the goal of interrupting maladaptive feedback loops and supporting improved autonomic and emotional regulation. In this randomized pilot study, individuals with MS will be assigned to one of three groups: a lifestyle education program, the AIR program, or a wait-list control group. By comparing changes in validated symptom and quality-of-life measures across groups over time, this study aims to generate preliminary data on the feasibility and potential symptom-modifying effects of both interventions, informing the design of larger, controlled trials.