title: Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder.
abstract: BACKGROUND
  The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD).
  
  
  RESULTS
  Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome.
  
  
  CONCLUSIONS
  These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Tiago
authors: T
authors: Simas
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Shayanti
authors: S
authors: Chattopadhyay
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Psychology, Columbia University, New York, New York, United States of America.
authors: Cindy
authors: C
authors: Hagan
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors: Prantik
authors: P
authors: Kundu
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Ameera
authors: A
authors: Patel
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Rosemary
authors: R
authors: Holt
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Dorothea
authors: D
authors: Floris
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, University of Oxford, Medical Sciences Division, Oxford, United Kingdom.
authors: Julia
authors: J
authors: Graham
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Cinly
authors: C
authors: Ooi
authors: MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Roger
authors: R
authors: Tait
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Michael
authors: M
authors: Spencer
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Simon
authors: S
authors: Baron-Cohen
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Barbara
authors: B
authors: Sahakian
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridge and Peterborough Foundation NHS Trust, Cambridge, United Kingdom; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Ed
authors: E
authors: Bullmore
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridge and Peterborough Foundation NHS Trust, Cambridge, United Kingdom; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Ian
authors: I
authors: Goodyer
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridge and Peterborough Foundation NHS Trust, Cambridge, United Kingdom; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors: John
authors: J
authors: Suckling
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000473:pathology*; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D002648:Child; D063132:Connectome / Q000379:methods*; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods; D012680:Sensitivity and Specificity; D013702:Temporal Lobe / Q000503:physiopathology*