title: Frontal cortex BOLD signal changes in premanifest Huntington disease: a possible fMRI biomarker.
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 (r(2) = 0.52). Among the considered striatal volumes, a modest correlation (r(2) = 0.29) was observed in the right putamen and p5HD.
  
  
  CONCLUSIONS
  fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferraro
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco. nanetti.l@istituto-besta.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nanetti
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Piacentini
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mandelli
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bertolino
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ghielmetti
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Francesca
authors.initials: F
authors.lastname: Epifani
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Anna
authors.initials: A
authors.lastname: Nigri
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Donato
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Mario
authors.initials: M
authors.lastname: Savoiardo
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.affiliation: From the Neuroradiology Department (S.F., F.G., F.E., A.N., M.G.B., M.S., M.G.), Unit of Genetics of Neurodegenerative and Metabolic Diseases, Clinical Pathology and Medical Genetics (L.N., F.T., S.D., C.M.), and Health Department (S.P., N.B., F.G.), Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy; and the Memory and Aging Center (M.L.M.), Department of Neurology, University of California San Francisco.
authors.forename: Marina
authors.initials: M
authors.lastname: Grisoli
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000473:pathology; D055815:Young Adult
chemical_list: D010100:Oxygen