Open AccessFunctional brain changes underlying irritability in premanifest H untington's disease
Author(s) -
Van den Stock Jan,
De Winter FrançoisLaurent,
Ahmad Rawaha,
Sunaert Stefan,
Van Laere Koen,
Vandenberghe Wim,
Vandenbulcke Mathieu
Publication year - 2015
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.22799
Subject(s) - irritability , grey matter , psychology , anger , amygdala , neuroscience , anterior cingulate cortex , emotional dysregulation , insular cortex , clinical psychology , medicine , audiology , cognition , white matter , magnetic resonance imaging , radiology
Abstract The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene‐negative controls from HD families took part in the study. Although the 5‐year probability of disease onset was only 11%, the preHD group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, and happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the preHD group showed increased anger‐selective activation in a distributed network, including the pulvinar, cingulate cortex, and somatosensory association cortex, compared to gene‐negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability rating s in the preHD group. In addition, the preHD group showed a decrease in anger‐selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene‐negative controls, anger experience in preHD is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in preHD. Hum Brain Mapp 36:2681–2690, 2015 . © 2015 Wiley Periodicals, Inc .