title: Longitudinal Changes in the Motor Learning-Related Brain Activation Response in Presymptomatic Huntington's Disease.
abstract: Neurocognitive decline, including deficits in motor learning, occurs in the presymptomatic phase of Huntington's disease (HD) and precedes the onset of motor symptoms. Findings from recent neuroimaging studies have linked these deficits to alterations in fronto-striatal and fronto-parietal brain networks. However, little is known about the temporal dynamics of these networks when subjects approach phenoconversion. Here, 10 subjects with presymptomatic HD were scanned with 15O-labeled water at baseline and again 1.5 years later while performing a motor sequence learning task and a kinematically matched control task. Spatial covariance analysis was utilized to characterize patterns of change in learning-related neural activation occurring over time in these individuals. Pattern expression was compared to corresponding values in 10 age-matched healthy control subjects. Spatial covariance analysis revealed significant longitudinal changes in the expression of a specific learning-related activation pattern characterized by increasing activity in the right orbitofrontal cortex, with concurrent reductions in the right medial prefrontal and posterior cingulate regions, the left insula, left precuneus, and left cerebellum. Changes in the expression of this pattern over time correlated with baseline measurements of disease burden and learning performance. The network changes were accompanied by modest improvement in learning performance that took place concurrently in the gene carriers. The presence of increased network activity in the setting of stable task performance is consistent with a discrete compensatory mechanism. The findings suggest that this effect is most pronounced in the late presymptomatic phase of HD, as subjects approach clinical onset.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Florian
authors.initials: F
authors.lastname: Holtbernd
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Tang
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of Neurology, Northwell Health, Manhasset, New York, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Feigin
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, City University of New York Medical School, New York, New York, United States of America.
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Ghilardi
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.affiliation: Department of Neurology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Guttman
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of Neurology, Northwell Health, Manhasset, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D016022:Case-Control Studies; D002531:Cerebellum / Q000000981:diagnostic imaging; D063132:Connectome; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007858:Learning; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D011597:Psychomotor Performance