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Abstract
Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset.
Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD.
Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r2 = 0.52). Among the considered striatal volumes, a modest correlation (r2 = 0.29) was observed in the right putamen and p5HD.
Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.
GLOSSARY
- ANOVA=
- analysis of variance;
- BOLD=
- blood oxygen level–dependent;
- COVAT=
- covert orienting of spatial attention;
- FEF=
- frontal eye field;
- fMRI=
- functional MRI;
- FWE=
- family-wise error;
- HD=
- Huntington disease;
- IOR=
- inhibition of return;
- p5HD=
- probability to develop Huntington disease onset in the next 5 years;
- preHD=
- premanifest Huntington disease;
- PST=
- prosaccadic task;
- ROI=
- region of interest;
- RT=
- reaction times;
- SOA=
- stimulus onset asynchrony;
- TE=
- echo time;
- TR=
- repetition time
Footnotes
↵† Deceased.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received July 13, 2013.
- Accepted in final form February 18, 2014.
- © 2014 American Academy of Neurology
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