title: Subcallosal Cingulate Connectivity in Anorexia Nervosa Patients Differs From Healthy Controls: A Multi-tensor Tractography Study.
abstract: BACKGROUND
  Anorexia nervosa is characterized by extreme low body weight and alterations in affective processing. The subcallosal cingulate regulates affect through wide-spread white matter connections and is implicated in the pathophysiology of anorexia nervosa.
  
  
  OBJECTIVE
  We examined whether those with treatment refractory anorexia nervosa undergoing deep brain stimulation (DBS) of the subcallosal white matter (SCC) show: (1) altered anatomical SCC connectivity compared to healthy controls, (2) white matter microstructural changes, and (3) microstructural changes associated with clinically-measured affect.
  
  
  METHODS
  Diffusion magnetic resonance imaging (dMRI) and deterministic multi-tensor tractography were used to compare anatomical connectivity and microstructure in SCC-associated white matter tracts. Eight women with treatment-refractory anorexia nervosa were compared to 8 age- and sex-matched healthy controls. Anorexia nervosa patients also completed affect-related clinical assessments presurgically and 12 months post-surgery.
  
  
  RESULTS
  (1) Higher (e.g., left parieto-occipital cortices) and lower (e.g., thalamus) connectivity in those with anorexia nervosa compared to controls. (2) Decreases in fractional anisotropy, and alterations in axial and radial diffusivities, in the left fornix crus, anterior limb of the internal capsule (ALIC), right anterior cingulum and left inferior fronto-occipital fasciculus. (3) Correlations between dMRI metrics and clinical assessments, such as low pre-surgical left fornix and right ALIC fractional anisotropy being related to post-DBS improvements in quality-of-life and depressive symptoms, respectively.
  
  
  CONCLUSIONS
  We identified widely-distributed differences in SCC connectivity in anorexia nervosa patients consistent with heterogenous clinical disruptions, although these results should be considered with caution given the low number of subjects. Future studies should further explore the use of affect-related connectivity and behavioral assessments to assist with DBS target selection and treatment outcome.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Dave J
authors.initials: DJ
authors.lastname: Hayes
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Nir
authors.initials: N
authors.lastname: Lipsman
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
authors.forename: David Q
authors.initials: DQ
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
authors.forename: D Blake
authors.initials: DB
authors.lastname: Woodside
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Davis
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto Western Research Institute, Division of Brain, Imaging and Behaviour - Systems Neuroscience, University Health Network, Toronto, Ontario M5T 2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. Electronic address: Mojgan.hodaie@uhn.ca.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Hodaie
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000503:physiopathology* / Q000628:therapy*; D016022:Case-Control Studies; D046690:Deep Brain Stimulation; D056324:Diffusion Tensor Imaging; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009434:Neural Pathways / Q000503:physiopathology*; D066127:White Matter / Q000473:pathology / Q000502:physiology*; D055815:Young Adult
keywords: DTI; Deep brain stimulation; Diffusion tensor imaging; Eating disorder; Fractional anisotropy; Mood disorder