{
  "abstract": "Restless legs syndrome (RLS) is a clinically heterogeneous sensorimotor disorder whose pathophysiology reflects interacting biological mechanisms rather than a single causal pathway. Established influences—including brain iron biology, dopaminergic regulation, glutamatergic and GABAergic balance, adenosinergic inhibition, and abnormal afferent processing—have typically been studied in isolation, leaving their systems-level relationships insufficiently integrated. To motivate a network-based interpretation, we present three illustrative clinical phenotypes: dopamine-agonist augmentation, sensory-predominant RLS with inadequate response to pregabalin, and persistent symptoms despite partial correction of peripheral iron deficiency. These cases highlight how distinct upstream contexts can converge on similar sensory and sleep-physiological endpoints. Human neuroimaging and neurochemical studies provide convergent evidence for thalamic involvement in RLS, including altered thalamic connectivity, differences in thalamic nuclei and network organization, and increased thalamic glutamate/glutamine signal associated with disturbed sleep. Because the thalamus integrates sensory gating, motor modulation, arousal regulation, and sleep–wake stability, it represents a plausible convergence hub for upstream biological influences. We therefore propose a thalamus-centered convergence model in which iron deficiency, dopaminergic instability, glutamatergic hyperresponsiveness, reduced adenosinergic inhibition, altered GABAergic modulation, and abnormal afferent processing interact to increase the susceptibility of thalamo-cortical networks to sensory and arousal instability. The model does not replace established frameworks; instead, it organizes them within a unified, testable network architecture. We outline six falsifiable predictions for multimodal imaging, sleep microstructure, sensory physiology, and treatment-response studies, providing a structured basis for future mechanistic investigation of RLS.",
  "abstract_shown": true,
  "affiliations": [
    "Doctoral School, Semmelweis University, Budapest, Hungary",
    "Department of Neurology, The University of Pécs, Pécs, Hungary",
    "Department of Obstetrics and Gynecology, University of Szeged, Szeged, Hungary"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Beatrix Vághy"
    },
    {
      "affs": [
        1
      ],
      "name": "Sámuel Komoly"
    },
    {
      "affs": [
        0
      ],
      "name": "Szabolcs Várbíró"
    },
    {
      "affs": [
        2
      ],
      "name": "Szabolcs Várbíró"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0d6sbzteaex98.bib",
  "cited_by": 0,
  "doi": "10.3389/fnhum.2026.1977941",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fnhum.2026.1977941/full",
  "id": "0d6sbzteaex98",
  "issns": [
    "1662-5161"
  ],
  "landing_url": "https://doi.org/10.3389/fnhum.2026.1977941",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC321-571"
    ],
    [
      "openalex",
      "2713|Restless Legs Syndrome Research"
    ]
  ],
  "openalex": "W7223396301",
  "pdf_url": "https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2026.1977941/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/0d6sbzteaex98.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:25Z",
      "native_id": "14551ec12d414562823ce2dc11cfcf95",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fnhum.2026.1977941"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Restless Legs Syndrome Research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "A thalamus-centered network model of restless legs syndrome: an integrative hypothesis illustrated by three clinical phenotypes",
  "title_text": "A thalamus-centered network model of restless legs syndrome: an integrative hypothesis illustrated by three clinical phenotypes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:11Z",
  "url": "https://research.draconitic.com/paper/0d6sbzteaex98",
  "venue": "Frontiers in Human Neuroscience",
  "versions": []
}