Compensation in preclinical Huntington's disease: Evidence from the track-on hd study

Journal article


Kloppel, Stefan, Gregory, Sarah, Scheller, Elisa, Minkova, Lora, Razi, Adeel, Durr, Alexandra, Roos, Raymund A. C., Leavitt, Blair R., Papoutsi, Marina, Landwehrmeyer, G. Bernhard, Reilmann, Ralf, Borowsky, Beth, Johnson, Hans, Mills, James A., Owen, Gail N., Stout, Julie C., Scahill, Rachael I., Long, Jeffrey D., Rees, Geraint, ... Orth, M.. (2015) Compensation in preclinical Huntington's disease: Evidence from the track-on hd study. EBioMedicine. 2(10), pp. 1420 - 1429. https://doi.org/10.1016/j.ebiom.2015.08.002
AuthorsKloppel, Stefan, Gregory, Sarah, Scheller, Elisa, Minkova, Lora, Razi, Adeel, Durr, Alexandra, Roos, Raymund A. C., Leavitt, Blair R., Papoutsi, Marina, Landwehrmeyer, G. Bernhard, Reilmann, Ralf, Borowsky, Beth, Johnson, Hans, Mills, James A., Owen, Gail N., Stout, Julie C., Scahill, Rachael I., Long, Jeffrey D., Rees, Geraint, Tabrizi, Sarah J., Coleman, Allison J., Decolongon, J, Fan, M., Koren, T., Jauffret, Céline, Justo, Damian, Lehericy, Stephane, Nigaud, Kevin, Valabrègue, Romain, Schoonderbeek, A., t'Hart, E. P., Crawford, H., Johnson, Eileanoir, Read, Joy, Berna, C., Moss, D. Hensman, Craufurd, David I. O., Weber, Nathan, Labuschagne, Izelle and Orth, M.
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.

KeywordsHuntington's disease; preclinical; neural compensation; MRI; cognitive; motor
Year2015
JournalEBioMedicine
Journal citation2 (10), pp. 1420 - 1429
PublisherElsevier
ISSN2352-3964
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ebiom.2015.08.002
Scopus EID2-s2.0-84951905557
Open accessOpen access
Page range1420 - 1429
Research GroupSchool of Philosophy
Publisher's version
Additional information

© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Place of publicationNetherlands
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Labuschagne, Izelle, Phan, K. Luan, Wood, Amanda G., Angstadt, Mike, Chua, Phyllis, Heinrichs, Markus, Stout, Julie C. and Nathan, Pradeep. (2010) Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 35(12), pp. 2403 - 2413. https://doi.org/10.1038/npp.2010.123
Augmenting serotonin neurotransmission with citalopram modulates emotional expression decoding but not structural encoding of moderate intensity sad facial emotional stimuli: An event-related potential (ERP) investigation
Labuschagne, Izelle, Croft, Rodney, Phan, K. Luan and Nathan, Pradeep. (2010) Augmenting serotonin neurotransmission with citalopram modulates emotional expression decoding but not structural encoding of moderate intensity sad facial emotional stimuli: An event-related potential (ERP) investigation. Journal of Psychopharmacology. 24(8), pp. 1153 - 1164. https://doi.org/10.1177/0269881108097878
Executive function in body dysmorphic disorder
Dunai, Judith, Labuschagne, Izelle, Castle, David J., Kyrios, Michael and Rossell, Susan. (2010) Executive function in body dysmorphic disorder. Psychological Medicine. 40(9), pp. 1541 - 1548. https://doi.org/10.1017/S003329170999198X
An examination of delusional thinking and cognitive styles in body dysmorphic disorder
Labuschagne, Izelle, Castle, David J., Dunai, Judith, Kyrios, Michael and Rossell, Susan. (2010) An examination of delusional thinking and cognitive styles in body dysmorphic disorder. Australian and New Zealand Journal of Psychiatry. 44(8), pp. 706 - 712. https://doi.org/10.3109/00048671003671007
Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: An event-related potential (ERP) study
Kerestes, Rebecca, Labuschagne, Izelle, Croft, Rodney, O'Neill, Barry, Bhagwagar, Zubin M., Phan, K Luan and Nathan, Pradeep. (2009) Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: An event-related potential (ERP) study. Psychopharmacology. 202(4), pp. 621 - 634. https://doi.org/10.1007/s00213-008-1340-3