title: Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study.
abstract: BACKGROUND
  Cognitive and motor task performance in premanifest Huntington's disease (HD) gene-carriers is often within normal ranges prior to clinical diagnosis, despite loss of brain volume in regions involved in these tasks. This indicates ongoing compensation, with the brain maintaining function in the presence of neuronal loss. However, thus far, compensatory processes in HD have not been modeled explicitly. Using a new model, which incorporates individual variability related to structural change and behavior, we sought to identify functional correlates of compensation in premanifest-HD gene-carriers.
  
  
  METHODS
  We investigated the modulatory effects of regional brain atrophy, indexed by structural measures of disease load, on the relationship between performance and brain activity (or connectivity) using task-based and resting-state functional MRI.
  
  
  RESULTS
  Consistent with compensation, as atrophy increased performance-related activity increased in the right parietal cortex during a working memory task. Similarly, increased functional coupling between the right dorsolateral prefrontal cortex and a left hemisphere network in the resting-state predicted better cognitive performance as atrophy increased. Such patterns were not detectable for the left hemisphere or for motor tasks.
  
  
  CONCLUSIONS
  Our findings provide evidence for active compensatory processes in premanifest-HD for cognitive demands and suggest a higher vulnerability of the left hemisphere to the effects of regional atrophy.
authors.affiliation: Albert-Ludwigs-University Freiburg, University Medical Center, Division Freiburg Brain Imaging, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, University Medical Center, Department of Psychiatry and Psychotherapy, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, University Medical Center, Department of Neurology, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gregory
authors.affiliation: Albert-Ludwigs-University Freiburg, University Medical Center, Division Freiburg Brain Imaging, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, University Medical Center, Department of Psychiatry and Psychotherapy, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, Department of Psychology, Laboratory for Biological and Personality Psychology, Freiburg, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Scheller
authors.affiliation: Albert-Ludwigs-University Freiburg, University Medical Center, Division Freiburg Brain Imaging, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, University Medical Center, Department of Psychiatry and Psychotherapy, Freiburg, Germany ; Albert-Ludwigs-University Freiburg, Department of Psychology, Laboratory for Biological and Personality Psychology, Freiburg, Germany.
authors.forename: Lora
authors.initials: L
authors.lastname: Minkova
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK ; Department of Electronic Engineering, N.E.D University of Engineering & Technology, Karachi, Pakistan.
authors.forename: Adeel
authors.initials: A
authors.lastname: Razi
authors.affiliation: APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, UPMC Université Paris VI UMR_S1127, Paris France ; Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, UPMC Université Paris VI UMR_S1127, Paris France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Canada.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Papoutsi
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: G Bernhard
authors.initials: GB
authors.lastname: Landwehrmeyer
authors.affiliation: George-Huntington-Institute, Muenster, Germany ; University of Tuebingen, Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, Tuebingen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
authors.affiliation: CHDI Management/CHDI Foundation, Princeton, NJ, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Borowsky
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Mills
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Owen
authors.affiliation: School of Psychological Sciences and Institute of Clinical and Cognitive Neuroscience, Monash University, Melbourne, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Stout
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA ; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK ; Institute of Cognitive Neuroscience, University College London, London, UK.
authors.forename: Geraint
authors.initials: G
authors.lastname: Rees
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D016022:Case-Control Studies; D063132:Connectome; D005260:Female; D006579:Heterozygote; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011597:Psychomotor Performance
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: Cognitive; Huntington's disease; MRI; Motor; Neural compensation; Preclinical