title: Large-scale changes in network interactions as a physiological signature of spatial neglect.
abstract: The relationship between spontaneous brain activity and behaviour following focal injury is not well understood. Here, we report a large-scale study of resting state functional connectivity MRI and spatial neglect following stroke in a large (n=84) heterogeneous sample of first-ever stroke patients (within 1-2 weeks). Spatial neglect, which is typically more severe after right than left hemisphere injury, includes deficits of spatial attention and motor actions contralateral to the lesion, and low general attention due to impaired vigilance/arousal. Patients underwent structural and resting state functional MRI scans, and spatial neglect was measured using the Posner spatial cueing task, and Mesulam and Behavioural Inattention Test cancellation tests. A principal component analysis of the behavioural tests revealed a main factor accounting for 34% of variance that captured three correlated behavioural deficits: visual neglect of the contralesional visual field, visuomotor neglect of the contralesional field, and low overall performance. In an independent sample (21 healthy subjects), we defined 10 resting state networks consisting of 169 brain regions: visual-fovea and visual-periphery, sensory-motor, auditory, dorsal attention, ventral attention, language, fronto-parietal control, cingulo-opercular control, and default mode. We correlated the neglect factor score with the strength of resting state functional connectivity within and across the 10 resting state networks. All damaged brain voxels were removed from the functional connectivity:behaviour correlational analysis. We found that the correlated behavioural deficits summarized by the factor score were associated with correlated multi-network patterns of abnormal functional connectivity involving large swaths of cortex. Specifically, dorsal attention and sensory-motor networks showed: (i) reduced interhemispheric functional connectivity; (ii) reduced anti-correlation with fronto-parietal and default mode networks in the right hemisphere; and (iii) increased intrahemispheric connectivity with the basal ganglia. These patterns of functional connectivity:behaviour correlations were stronger in patients with right- as compared to left-hemisphere damage and were independent of lesion volume. Our findings identify large-scale changes in resting state network interactions that are a physiological signature of spatial neglect and may relate to its right hemisphere lateralization.
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA 2 Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti G. d'Annunzio, via dei Vestini 33, 66013, Chieti, Italy 3 Institute for Advanced Biomedical Technologies, G. d'Annunzio University Foundation, University of Chieti G. d'Annunzio, via dei Vestini 33, 66013, Chieti, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Baldassarre
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Lenny
authors.initials: L
authors.lastname: Ramsey
authors.affiliation: 4 Department of Biomedical Engineering, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
authors.forename: Carl L
authors.initials: CL
authors.lastname: Hacker
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Callejas
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Serguei V
authors.initials: SV
authors.lastname: Astafiev
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Metcalf
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Zinn
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rengachary
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA 5 Department of Radiology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Carter
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Shulman
authors.affiliation: 1 Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA 2 Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti G. d'Annunzio, via dei Vestini 33, 66013, Chieti, Italy 3 Institute for Advanced Biomedical Technologies, G. d'Annunzio University Foundation, University of Chieti G. d'Annunzio, via dei Vestini 33, 66013, Chieti, Italy 4 Department of Biomedical Engineering, Washington University in St. Louis School of Medicine, St. Louis, MO, USA 5 Department of Radiology, Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA 6 Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine,660 S Euclid Ave, St. Louis, MO 63110, USA mau@npg.wustl.edu.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Corbetta
mesh_terms: D000328:Adult; D000368:Aged; D001288:Attention / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology; D010468:Perceptual Disorders / Q000503:physiopathology*; D013028:Space Perception; D020521:Stroke / Q000503:physiopathology; D055815:Young Adult
keywords: functional MRI; functional connectivity; resting-state; stroke