Integrating Neural Noise and Neuroinflammatory Hypotheses: Exploring the Comorbidity of Dyslexia, Depression, and Stress

Fumiko Hoeft

Recent advancements in our understanding of dyslexia have highlighted the complex interplay between neurobiological mechanisms and comorbid conditions such as depression and stress. The Neural Noise Hypothesis (NNH) of dyslexia proposes that dysregulated neural activity, characterized by excessive glutamatergic neurotransmission, leads to the disrupted auditory and visual processing that typifies this learning disorder. Concurrently, emerging research suggests that these neural irregularities may overlap with pathways involved in stress and depression, pointing to a shared neurobiological foundation. This presentation explores the synthesis of the NNH with recent findings on the role of neuroinflammation in dyslexia and its comorbidities. Building on our foundational work (Hancock, Pugh, and Hoeft, TiCS. 2017), and integrating recent insights into stress and mood disorders from neuroimaging studies, we propose a model where dyslexia-related neural noise may exacerbate susceptibility to depression through neuroinflammatory pathways. This model is supported by recent research by Lasnick and Hoeft (Front Hum Neurosci. 2023), which provides compelling evidence of altered neural connectivity in regions critical for emotional and stress regulation in individuals with dyslexia. Furthermore, this talk will delve into how environmental stressors and individual resilience factors contribute to the variability in dyslexia presentations, particularly focusing on how these elements interact with neurobiological mechanisms to influence the severity and range of comorbid symptoms. By bridging gaps between disparate research domains, we aim to foster a more comprehensive understanding of dyslexia that acknowledges its potential as a multisystem disorder with significant neurobiological and psychosocial dimensions. This integrated approach sets the stage for discussing potential interventions that target these overlapping pathways, offering hope for more effective treatments that address both the core symptoms of dyslexia and its common comorbidities.