Eye-tracking in Early Manifest Huntington’s Disease: Heterogeneity of Deficits in Inhibitory and Fronto-Executive Control
Main Article Content
Abstract
Objectives: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that affects first basal ganglia and fronto- striatal circuitry. Cognitive decline and inhibitory control deficits are more subtle in the early stages of manifest disease, yet relevant to track disease progression. The current study aims to underpin and characterize the dysfunction of oculomotor inhibitory control mechanisms and executive function through working memory demands on fronto-executive load in a cohort of early manifest HD (Early-HD).
Methods: A comprehensive battery of neuropsychological tests was applied to assess cognitive functioning in 14 Early-HD and 22 Control participants. Oculomotor function was studied using an experimental paradigm comprising four oculomotor tasks: prosaccade, antisaccade, 1- or 2-back memory prosaccade, and 1- or 2-back memory antisaccade. The estimated metrics were success rate, direction errors, timing errors, and the primary saccade latency.
Results: The Early-HD group demonstrated cognitive deficits in visual and verbal memory, executive function, attention, visual perception, and verbal and non-verbal IQ domains. Regarding oculomotor performance, the clinical group had a decreased success rate and increased percentage of direction errors and early premature saccades while exhibiting faster response times than the Control group in the 1- or 2-back memory antisaccade task.
Conclusions: Our results demonstrate overt oculomotor dysfunction in Early-HD since inhibitory control mechanisms are necessary to perform the task. Furthermore, increasing working memory demands and fronto-executive load enhances impulsive response patterns. The dysfunction in goal-oriented oculomotor behavior, including more automatized responses and deficits in inhibition, is present in Early- HD patients with cognitive deficits but who remain functional and autonomous. These findings reinforce the notion that fronto-striatal impairment is a crucial event in HD and that more automatized oculomotor evaluation procedures help identify and stratify deficits in early manifest disease.
Keywords:
Huntington’s disease, manifest stage, oculomotor performance, inhibition, fronto-executive load
Article Details
How to Cite
JÚLIO, Filipa et al.
Eye-tracking in Early Manifest Huntington’s Disease: Heterogeneity of Deficits in Inhibitory and Fronto-Executive Control.
Medical Research Archives, [S.l.], v. 12, n. 7, july 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5577>. Date accessed: 05 aug. 2024.
doi: https://doi.org/10.18103/mra.v12i7.5577.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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17. Paulsen JS, Long JD, Johnson HJ, et al. Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study. Front Aging Neurosci. 2014;6:78.
18. Domínguez JF, Stout JC, Poudel G, et al. Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data. British Journal of Psychiatry. 2018;208(6):571-578.
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21. Langbehn DR, Hayden MR, Paulsen JS, Group P-HIotHS. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2010;153B(2):397–408.
22. Lavrador R, Júlio F, Januário C, Castelo-Branco M, Caetano G. Classification of Huntington’s Disease Stage with Features Derived from Structural and Diffusion-Weighted Imaging. Journal of Personalized Medicine. 2022;12(5):704.
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26. Liu CF, Younes L, Tong XJ, et al. Longitudinal imaging highlights preferential basal ganglia circuit atrophy in Huntington's disease. Brain Commun. 2023;5(5):fcad214.
27. Estevez-Fraga C, Scahill R, Rees G, Tabrizi SJ, Gregory S. Diffusion imaging in Huntington’s disease: comprehensive review. Journal of Neurology, Neurosurgery & Psychiatry. 2021;92(1):62.
28. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP. Neuropathological Classification of Huntingtons-Disease. J Neuropath Exp Neur. 1985;44(6):559–577.
29. Paulsen JS, Long JD. Onset of Huntington's disease: can it be purely cognitive? Mov Disord. 2014;29(11):1342-1350.
30. Biglan KM, Zhang Y, Long JD, et al. Refining the diagnosis of Huntington disease: the PREDICT-HD study. Front Aging Neurosci. 2013;5:12.
31. Harrington DL, Smith MM, Zhang Y, Carlozzi NE, Paulsen JS, Group tP-HIotHS. Cognitive domains that predict time to diagnosis in prodromal Huntington disease. Journal of Neurology, Neurosurgery & Psychiatry. 2012;83(6):612-619.
32. Stout JC, Paulsen JS, Queller S, et al. Neurocognitive Signs in Prodromal Huntington Disease. Neuropsychology. 2011;25(1):1-14.
33. Zimbelman JL, Paulsen JS, Mikos A, Reynolds NC, Hoffmann RG, Rao SM. fMRI detection of early neural dysfunction in preclinical Huntington's disease. Journal of the International Neuropsychological Society. 2007;13(5):758-769.
34. Ross CA, Pantelyat A, Kogan J, Brandt J. Determinants of Functional Disability in Huntington's Disease: Role of Cognitive and Motor Dysfunction. Movement Disorders. 2014;29(11):1351-1358.
35. Dumas EM, van den Bogaard SJ, Middelkoop HA, Roos RA. A review of cognition in Huntington's disease. Frontiers in Bioscience (Schol Ed). 2013;5:1-18.
36. Carvalho JO, Long JD, Westervelt HJ, et al. The impact of oculomotor functioning on neuropsychological performance in Huntington disease. J Clin Exp Neuropsyc. 2016;38(2):217-226.
37. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society. 2005;53(4):695-699.
38. Bechtel N, Scahill RI, Rosas HD, et al. Tapping linked to function and structure in premanifest and symptomatic Huntington disease. Neurology. 2010;75(24):2150-2160.
39. Anderson TJ, MacAskill MR. Eye movements in patients with neurodegenerative disorders. Nat Rev Neurol. 2013;9(2):74-85.
40. Cutsuridis V, Jiang S, Dunn MJ, Rosser A, Brawn J, Erichsen JT. Neural modeling of antisaccade performance of healthy controls and early Huntington's disease patients. Chaos (Woodbury, NY). 2021;31(1):013121.
41. Miranda A, Lavrador R, Julio F, Januario C, Castelo-Branco M, Caetano G. Classification of Huntington's disease stage with support vector machines: A study on oculomotor performance. Behav Res Methods. 2016;48(4):1667-1677.
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