Neural Correlates of Huntington’s Disease Based on Electroencephalography (EEG): A Mechanistic Review and Discussion of Excitation and Inhibition (E/I) Imbalance

Introduction: Huntington's disease (HD) disrupts cortico-striato-thalamocortical circuits decades before clinical onset. Electroencephalography (EEG) offers millisecond temporal resolution, low cost, and broad accessibility, yet its mechanistic and biomarker potential in HD remains underexplored. We conducted a mechanistic review to synthesize half a century of EEG findings, identify reproducible electrophysiological signatures, and outline translational next steps. Methods: Two independent reviewers searched PubMed, Scopus, Google Scholar, ResearchGate, and the Cochrane Library (January 1970-April 2025) using the terms "EEG" OR "electroencephalography" AND "Huntington's disease". Clinical trials published in English that reported raw EEG (not ERP-only) in human HD gene carriers were eligible. Abstract/title screening, full-text appraisal, and cross-reference mining yielded 22 studies (~700 HD recordings, ~600 controls). We extracted sample characteristics, acquisition protocols, spectral/connectivity metrics, and neuroclinical correlations. Results: Across diverse platforms, a consistent spectral trajectory emerged: (i) presymptomatic carriers show a focal 7-9 Hz (low-alpha) power loss that scales with CAG repeat length; (ii) early-manifest patients exhibit widespread alpha attenuation, delta-theta excess, and a flattened anterior-posterior gradient; (iii) advanced disease is characterized by global slow-wave dominance and low-voltage tracings. Source-resolved studies reveal early alpha hypocoherence and progressive delta/high-beta hypersynchrony, microstate shifts (A/B ↑, C/D ↓), and rising omega complexity. These electrophysiological changes correlate with motor burden, cognitive slowing, sleep fragmentation, and neurovascular uncoupling, and achieve 80-90% diagnostic accuracy in shallow machine-learning pipelines. Conclusions: EEG offers a coherent, stage-sensitive window on HD pathophysiology-from early thalamocortical disinhibition to late network fragmentation-and fulfills key biomarker criteria. Translation now depends on large, longitudinal, multi-center cohorts with harmonized high-density protocols, rigorous artifact control, and linkage to clinical milestones. Such infrastructure will enable the qualification of alpha-band restoration, delta-band hypersynchrony, and neurovascular coupling as pharmacodynamic readouts, fostering precision monitoring and network-targeted therapy in Huntington's disease.