title: Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the neural basis of subjective fatigue in subjects with multiple sclerosis (MS) using a connectionist framework.
  
  
  METHODS
  Seventy seven subjects with relapsing-remitting MS were recruited in the study and underwent subjective fatigue evaluations and a diffusion MRI scan. Firstly, local white matter Fractional Anisotropy values were correlated with subjective fatigue scores using a voxel-wise approach. The long-range loss of connectivity due to structural damage in the white matter voxels thus associated with subjective fatigue was then assessed using the Network Modification (NeMo) package.
  
  
  RESULTS
  A voxel-wise regression analysis with fatigue scores revealed a significant association between structural damage and fatigue levels in two discrete white matter clusters, both included in the left cingulate bundle. The connectivity analysis revealed that damage in these clusters was associated with loss of structural connectivity in the anterior and medial cingulate cortices, dorsolateral prefrontal areas and in the left caudate.
  
  
  CONCLUSIONS
  Our data point to the cingulum bundle and its projections as the key network involved in subjective fatigue perception in MS. More generally, these results suggest the potential of the connectionist framework to generate coherent models of the neural basis of complex symptomatology in MS.
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pardini
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonzano
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bergamino
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bommarito
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Feraco
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Abitha
authors.initials: A
authors.lastname: Murugavel
authors.affiliation: Section of Human Physiology and Centro Polifunzionale di Scienze Motorie, University of Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bove
authors.affiliation: Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Brichetto
authors.affiliation: University of Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.affiliation: Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy/Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
authors.affiliation: Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa/San Martino University Hospital/ University of Genoa, Genoa, Italy lroccatagliata@neurologia.unige.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
mesh_terms: D000328:Adult; D038524:Diffusion Magnetic Resonance Imaging; D005221:Fatigue / Q000209:etiology*; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000473:pathology*
keywords: White matter; cingulum bundle; diffusion tensor imaging; fatigue