title: Right anterior insula: core region of hallucinations in cognitive neurodegenerative diseases.
abstract: OBJECTIVE
  We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.
  
  
  METHODS
  AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. "Core regions" (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.
  
  
  RESULTS
  Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).
  
  
  CONCLUSIONS
  Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.
authors.affiliation: University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France; University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France; University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France; University Hospital of Strasbourg, Day Hospital of Geriatrics, Geriatrics Service, Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanc
authors.affiliation: University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Noblet
authors.affiliation: University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France; University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France; University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Philippi
authors.affiliation: University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France; University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France; University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cretin
authors.affiliation: University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.
authors.forename: Jack
authors.initials: J
authors.lastname: Foucher
authors.affiliation: University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Armspach
authors.affiliation: University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Rousseau
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006212:Hallucinations / Q000473:pathology*; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods; D049268:Positron-Emission Tomography