title: Neuro-cognitive mechanisms of simultanagnosia in patients with posterior cortical atrophy.
abstract: Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas. To test these distinct hypotheses, we investigated a group of 12 patients suffering from posterior cortical atrophy with homogenous lesion sides in parieto-occipital cortices and varying severity of grey and white matter loss. More specifically, we (i) tested whether impaired short-term memory capacity or processing speed underlie symptoms of simultanagnosia; (ii) assessed the link to grey and white matter damage; and (iii) integrated those findings into a neuro-cognitive model of simultanagnosia in patients with posterior cortical atrophy. To this end, simultaneous perception of multiple visual objects was tested in patients with posterior cortical atrophy mostly with positive Alzheimer's disease biomarkers and healthy age-matched controls. Critical outcome measures were identification of overlapping relative to non-overlapping figures and visuo-spatial performance in tests sensitive to simultanagnosia. Using whole report of briefly presented letter arrays based on the mathematically formulated 'Theory of Visual Attention', we furthermore quantified parameters of visual short-term memory capacity and visual processing speed. Grey and white matter atrophy was assessed by voxel-based morphometry analyses of structural magnetic resonance data. All patients showed severe deficits of simultaneous perception. Compared to controls, we observed a specific slowing of visual processing speed, while visual short-term memory capacity was preserved. In a regression analysis, processing speed was identified as the only significant predictor of simultaneous perception deficits that explained a high degree of variance (70-82%) across simultanagnosia tasks. More severe slowing was also indicative for more severe impairments in reading and scene comprehension. Voxel-based morphometry yielded extensive reductions of grey and white matter in parieto-occipital and thalamic brain areas. Importantly, the degree of individual atrophy of white matter in left superior parietal lobe, but not of any grey matter region, was associated with processing speed. Based on these findings, we propose that atrophy of white matter commonly observed in posterior cortical atrophy leads to slowing of visual processing speed, which underlies the overt clinical symptoms of simultanagnosia.
authors.affiliation: 1 General and Experimental Psychology, Department of Psychology, Ludwig-Maximilians-Universität München, Munich, Germany julia.neitzel@psy.lmu.de.|2 Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians-Universität München, Munich, Germany.|3 Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Neitzel
authors.affiliation: 4 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Ortner
authors.affiliation: 1 General and Experimental Psychology, Department of Psychology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Marleen
authors.initials: M
authors.lastname: Haupt
authors.affiliation: 1 General and Experimental Psychology, Department of Psychology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Redel
authors.affiliation: 4 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: 5 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
authors.affiliation: 6 Department of Nuclear Medicine, University Köln, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: 7 Hans-Berger Department of Neurology, University Hospital Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bublak
authors.affiliation: 7 Hans-Berger Department of Neurology, University Hospital Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Preul
authors.affiliation: 3 Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|4 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
authors.affiliation: 1 General and Experimental Psychology, Department of Psychology, Ludwig-Maximilians-Universität München, Munich, Germany.|2 Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Finke
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001284:Atrophy / Q000000981:diagnostic imaging; D001288:Attention / Q000502:physiology*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009778:Occipital Lobe / Q000000981:diagnostic imaging*; D010296:Parietal Lobe / Q000000981:diagnostic imaging*; D010468:Perceptual Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D013028:Space Perception / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: atypical Alzheimer’s disease; posterior cortical atrophy; simultanagnosia; theory of visual attention; voxel-based morphometry