Format

Send to

Choose Destination
EBioMedicine. 2015 Aug 4;2(10):1420-9. doi: 10.1016/j.ebiom.2015.08.002. eCollection 2015 Oct.

Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study.

Author information

1
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.
2
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK.
3
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.
4
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.
5
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.
6
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands.
7
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Canada.
8
Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
9
Department of Neurology, Ulm University, Ulm, Germany.
10
George-Huntington-Institute, Muenster, Germany ; University of Tuebingen, Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, Tuebingen, Germany.
11
CHDI Management/CHDI Foundation, Princeton, NJ, USA.
12
Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
13
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
14
School of Psychological Sciences and Institute of Clinical and Cognitive Neuroscience, Monash University, Melbourne, Australia.
15
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.
16
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK ; Institute of Cognitive Neuroscience, University College London, London, UK.

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.

FINDINGS:

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.

INTERPRETATION:

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.

KEYWORDS:

Cognitive; Huntington's disease; MRI; Motor; Neural compensation; Preclinical

PMID:
26629536
PMCID:
PMC4634199
DOI:
10.1016/j.ebiom.2015.08.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center