The Nitrosative-Excitotoxic Spectrum: Reclassifying Sensory, Cognitive, and Motor Disorders as Metabolic Failures of Central Gain Control

Preprint Notice: This is a preprint and has not undergone peer review. It is shared to invite critique, enable rapid dissemination, and support scientific discussion. It should not be used to guide clinical decision-making. Abstract: Current nosology treats visual snow syndrome (VSS), tinnitus, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) as distinct clinical entities divided by specialty boundaries. This paper proposes that these conditions arise from a shared pathophysiology: a specific metabolic failure of inhibitory “gain control” driven by dysregulation of the glutamate–NMDA–nitric oxide axis. We reframe these disorders not by their symptoms but by a common failure to filter neural noise (“sensory static”, “cognitive static”, and “motor static”), and present a unified model of nitrosative–excitotoxic gain failure. In this hypothesis, the plaques and tangles of neurodegeneration are downstream consequences rather than primary causes. The framework generates clear falsifiable predictions and suggests therapeutic points of intervention aimed at stabilising the excitatory–nitrosative loop before irreversible degeneration occurs. Plain-English Summary: This paper suggests that conditions such as visual snow, tinnitus, Alzheimer’s disease, and ALS may share a single biochemical loop involving glutamate, calcium influx through NMDA receptors, and nitric oxide. When this loop becomes self-reinforcing, inhibitory circuits lose the ability to suppress background neural noise. Depending on which circuits are affected, this appears as visual static, ringing in the ears, memory disruption, or motor instability. The hypothesis provides a unifying framework for research and outlines potential strategies for stabilising the underlying loop rather than targeting downstream pathology. Version: v1 (8 December 2025)