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Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.

ABSTRACT: Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regression analyses of cross-sectional MR images from 220 HD gene carriers and 75 controls in the Predict-HD study. We show that changes in the hypothalamic region are detectable before clinical diagnosis and that its grey matter contents alone are sufficient to distinguish HD gene carriers from control cases. In conclusion, our study shows, for the first time, that alterations in grey matter contents in the hypothalamic region occur at least a decade before clinical diagnosis in HD using MRI.

SUBMITTER: Soneson C

PROVIDER: S-EPMC2955781 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.

Soneson Charlotte C Fontes Magnus M Zhou Yongxia Y Denisov Vladimir V Paulsen Jane S JS Kirik Deniz D Petersén Asa A

Neurobiology of disease 20100802 3

Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regres ...[more]

PMID: 20682340

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Project description:Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control.

Dataset Information

Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.

Publications

Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.

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