A Resonance-Based Interpretation of Huntington's Disease Progression Within the Sympathetic Harmonic Resonance Framework (SHRF)

Abstract Huntington’s disease (HD) is classically defined as a monogenic neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. While the genetic origin is well established, disease onset, progression rate, and regional vulnerability vary substantially between individuals, even among those with similar inherited repeat lengths. Recent evidence highlights the role of somatic CAG expansion, early circuit dysfunction, and long premanifest phases marked by subtle cognitive and network changes. This paper proposes an interpretive framework for Huntington’s disease based on the Sympathetic Harmonic Resonance Framework (SHRF), in which biological systems are treated as multi-scale, phase-coupled resonant networks. Within this framework, mutant huntingtin acts as a progressive source of phase noise, degrading molecular, cellular, and neural coherence over time. Somatic repeat expansion is interpreted as a time-dependent detuning process, while early compensatory network dynamics reflect transient coherence preservation prior to failure. SHRF does not replace molecular or genetic models; rather, it provides a unifying dynamical layer that links genotype, cellular instability, network dysfunction, biomarkers, and emerging disease-modifying therapies. Testable predictions are proposed, particularly regarding early neural coherence signatures, compensation-collapse dynamics, and treatment response markers. Keywords Huntington’s disease, resonance, neural coherence, somatic expansion, corticostriatal circuits, phase synchrony, SHRF, neurodegeneration, systems neuroscience