{
  "abstract": "Background Visuospatial working memory (VSWM) deficits are among the earliest cognitive impairments evident in Huntington’s disease (HD). They often precede motor symptoms and likely reflect early disruption of cortico-striatal circuits. Both the cognitive components and brain correlates are, however, poorly delineated.Objectives This study aims to characterise the progression of VSWM deficits across HD stages and identify their structural brain correlates.Methods In this prospective international study, 92 HD mutation carriers (HDmc) (21 premanifest and 71 manifest) and 39 healthy controls underwent cognitive and clinical assessments and structural MRI at baseline; 49 manifest HD and 36 controls completed a 1-year follow-up. VSWM was assessed using the object–location task (OLT), providing continuous measures of location error, object recognition and object–location binding. MRI analyses included caudate, putamen and hippocampal volumes and cortical thickness.Results We found increased location error and spatial imprecision under high memory load, without binding errors in premanifest HD with an area under the curve of 0.731. Across all HDmc, these location deficits correlated with striatal atrophy and cortical thinning in parietal and middle cingulate regions. Manifest HD individuals exhibited swap errors and hippocampal atrophy. Both location and swap errors worsened over time alongside progressive striatal and hippocampal volume loss. Principal component analysis confirmed a dissociation between spatial location-related deficits (striato-cortically mediated) and binding errors (hippocampally mediated), supporting a hierarchical model of VSWM decline.Conclusions HD-related VSWM impairment follows a staged, anatomically dissociable trajectory. The OLT offers sensitive, mechanistic markers of cognitive decline with potential utility for early detection and clinical trial stratification.",
  "authors": [
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France"
      ],
      "name": "Marine Lunven"
    },
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France"
      ],
      "name": "Pamela Van Den Enden"
    },
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France"
      ],
      "name": "Andrès Gil Salcedo"
    },
    {
      "affiliations": [
        "Department of Psychology, Hebrew University of Jerusalem Faculty of Humanities, Jerusalem, Israel"
      ],
      "name": "Yoni Pertzov"
    },
    {
      "affiliations": [
        "Department of Neuroradiology, AP-HP, Henri Mondor University Hospital, Créteil, France",
        "Health Faculty, Université Paris-Est Créteil, Créteil, France"
      ],
      "name": "Blanche Bapst"
    },
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France",
        "Service de neurologie, centre de référence Maladie de Huntington, AP-HP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France",
        "Inserm, Centre d'Investigation Clinique 1430, APHP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France"
      ],
      "name": "Katia Youssov"
    },
    {
      "affiliations": [
        "Inserm, Centre d'Investigation Clinique 1430, APHP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France"
      ],
      "name": "Graça Morgado"
    },
    {
      "affiliations": [
        "Division of Digital Health and Applied Technology Assessment, King’s College London, London, UK",
        "Centre for Trials Research, Cardiff University, UK"
      ],
      "name": "Monica Busse"
    },
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France",
        "Service de neurologie, centre de référence Maladie de Huntington, AP-HP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France"
      ],
      "name": "Renaud Massart"
    },
    {
      "affiliations": [
        "Brain Repair Group, School of Biosciences, Life Science Building, Cardiff University, Cardiff, UK",
        "Neuroscience and Mental Health Institute, Hadyn Ellis Building, Cardiff School of Medicine, Cardiff, UK"
      ],
      "name": "Anne Rosser"
    },
    {
      "affiliations": [
        "Département d’Etudes Cognitives, PSL University, Paris, France",
        "Université Paris-Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale U955, Créteil, France",
        "Service de neurologie, centre de référence Maladie de Huntington, AP-HP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France",
        "Inserm, Centre d'Investigation Clinique 1430, APHP, Hôpital Henri Mondor-Albert Chenevier, Créteil, France"
      ],
      "name": "Anne-Catherine Bachoud-Lévi"
    }
  ],
  "title": "Visuospatial working memory in Huntington’s disease: behavioural and structural brain correlates",
  "uid": "e2152623-3e59-52a1-b170-eb37baa7714d"
}