Neural Correlates of Restless Legs Syndrome (RLS) Based on Electroencephalogram (EEG)—A Mechanistic Review

TL;DR

This review explores how brain activity patterns, measured by EEG, are linked to restless legs syndrome and suggests potential biomarkers for the condition.

Contribution

The paper identifies four reproducible EEG signatures in RLS patients that may serve as biomarkers for disease burden and treatment response.

Findings

Cortical hyperarousal at rest is marked by fronto-central beta elevation and a dissociated vigilance profile.

Attentional and working memory ERPs show attenuated and delayed P300 and reduced frontal P2, indicating fronto-parietal dysfunction.

Network inefficiency is observed through reduced theta/gamma synchrony and lower clustering/longer path length, correlating with symptom burden.

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder with evening-predominant symptoms; convergent models implicate brain iron dysregulation and alter dopaminergic/glutamatergic signaling. Because EEG provides millisecond-scale access to cortical dynamics, we synthesized waking EEG/ERP findings in RLS (sleep EEG excluded). A structured search across major databases (1980–July 2025) identified clinical EEG studies meeting prespecified criteria. Across small, mostly mid- to late-adult cohorts, four reproducible signatures emerged: (i) cortical hyperarousal at rest (fronto-central beta elevation with a dissociated vigilance profile); (ii) attentional/working memory ERPs with attenuated and delayed P300 (and reduced frontal P2), pointing to fronto-parietal dysfunction; (iii) network inefficiency (reduced theta/gamma synchrony and lower clustering/longer path length) that scales with symptom burden; and (iv) motor system abnormalities with exaggerated post-movement beta rebound and peri-movement cortical–autonomic co-activation, together with evening-vulnerable early visual processing during cognitive control. Dopamine agonist therapy partially normalizes behavior and ERP amplitudes. These converging EEG features provide candidate biomarkers for disease burden and treatment response and are consistent with models linking brain iron deficiency to thalamo-cortical timing failures. This mechanistic review did not adhere to PRISMA or PICO frameworks and did not include a formal risk-of-bias or quantitative meta-analysis; samples were small, heterogeneous, and English-only.

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