title: Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity.
abstract: BACKGROUND
  Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration.
  
  
  OBJECTIVE
  To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS.
  
  
  METHODS
  Structural and functional magnetic resonance imaging data were acquired for 57 MS patients and 28 healthy controls (HCs), yielding hippocampal measures of volume, lesions, functional activation during a memory task and functional connectivity at rest. Memory function was based on two subtests of a larger neuropsychological test battery and related to hippocampal neuroimaging measures, using linear regression.
  
  
  RESULTS
  Hippocampal volume was lower in MS patients, as compared to HCs. In MS, hippocampal activation during the task was increased in cognitively preserved, but decreased in cognitively impaired, patients. Increased hippocampal connectivity was detected in MS patients, as compared to HCs, between the left hippocampus and the right posterior cingulate. Memory impairment in MS was explained (adjusted R(2) = 0.27) by male gender, decreased hippocampal activation and increased hippocampal connectivity (p = 0.001).
  
  
  CONCLUSIONS
  Decreased activation of the hippocampus, increased connectivity and male gender were associated with worse memory performance in MS. These results indicate that increased activation and increased connectivity do not always coincide, and relate differently to cognitive dysfunction in MS.
authors: Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands he.hulst@vumc.nl.
authors: Hanneke E
authors: HE
authors: Hulst
authors: Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors: Menno M
authors: MM
authors: Schoonheim
authors: Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors: Quinten
authors: Q
authors: Van Geest
authors: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Bernard M J
authors: BM
authors: Uitdehaag
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors: Jeroen J G
authors: JJ
authors: Geurts
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D012737:Sex Factors
keywords: cognitive dysfunction; hippocampal activation; hippocampal connectivity; hippocampus; magnetic resonance imaging; memory; multiple sclerosis