{
  "abstract": "Fragile X syndrome (FXS), a leading monogenic cause of intellectual disability and autism-related features, results from loss of fragile X messenger ribonucleoprotein (FMRP). Although early synaptic and cellular abnormalities associated with the loss of FMRP are well described, it remains unclear how these changes shape the maturation of large-scale functional networks, or whether early pharmacological intervention can normalize circuit development. Our previous work demonstrated that cognitive deficits in Fmr1-/y rats emerge during development and can be prevented by brief early-life lovastatin treatment. Here, we asked whether large-scale functional connectivity (FC) shows a similarly dynamic developmental trajectory and whether early intervention alters its emergence. Using longitudinal resting-state functional magnetic resonance imaging (rsfMRI), we found that Fmr1-/y rats displayed an age-dependent FC phenotype, with increased connectivity within the retrosplenial cortex (RSC) at 4 weeks but reduced connectivity within the RSC and distributed brain networks by adulthood compared with wild-type controls. This suggests FC abnormalities emerge over development rather than representing a stable deficit. In contrast to its effects on cognitive measures, brief early-life lovastatin treatment rescues did not prevent the emergence of connectivity abnormalities. Reduced RSC FC was also observed in a small cohort of individuals with FXS (n = 5 per group), supporting further investigation of functional connectivity measures alongside behavioural and molecular endpoints in translational studies of FXS.",
  "abstract_shown": true,
  "affiliations": [
    "University of Edinburgh"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "J. Ye"
    },
    {
      "name": "J. A. B. Surl"
    },
    {
      "name": "A. G. McKechanie"
    },
    {
      "name": "O. Dando"
    },
    {
      "name": "M. Straathof"
    },
    {
      "name": "R. M. Dijkhuizen"
    },
    {
      "name": "A. C. Stanfield"
    },
    {
      "affs": [
        0
      ],
      "name": "S. M. Till"
    },
    {
      "name": "P. C. Kind"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/brsa4tsgt97xr.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.08.28.747531",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747531v1.full",
  "id": "brsa4tsgt97xr",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747531v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
    ]
  ],
  "openalex": "W7208723429",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747531v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/brsa4tsgt97xr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "10.64898/2026.08.28.747531",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747531v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Loss of FMRP leads to translationally relevant functional connectivity differences in a rat model of Fragile X Syndrome",
  "title_text": "Loss of FMRP leads to translationally relevant functional connectivity differences in a rat model of Fragile X Syndrome",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/brsa4tsgt97xr",
  "venue": "bioRxiv",
  "versions": []
}