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fMRI detection of early neural dysfunction in preclinical Huntington's disease

Published online by Cambridge University Press:  14 August 2007

JANICE L. ZIMBELMAN ,
JANE S. PAULSEN ,
ANIA MIKOS ,
NORMAN C. REYNOLDS ,
RAYMOND G. HOFFMANN  and
STEPHEN M. RAO
JANICE L. ZIMBELMAN
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Schey Center for Cognitive Neuroimaging, Cleveland Clinic Foundation, Cleveland, Ohio
JANE S. PAULSEN
Affiliation:
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa
ANIA MIKOS
Affiliation:
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa
NORMAN C. REYNOLDS
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
RAYMOND G. HOFFMANN
Affiliation:
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin
STEPHEN M. RAO
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Schey Center for Cognitive Neuroimaging, Cleveland Clinic Foundation, Cleveland, Ohio
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Abstract

Neuropsychological and neuroimaging changes have been observed in individuals with the Huntington's disease (HD) gene expansion prior to the onset of manifest HD. This cross-sectional fMRI study of preclinical HD (pre-HD) individuals was conducted to determine if functional brain changes precede deficits in behavioral performance and striatal atrophy. Twenty-six pre-HD and 13 demographically matched healthy participants performed a time reproduction task while undergoing fMRI scanning. Pre-HD participants were divided into two groups (n = 13 each): FAR (>12 years to estimated onset [YEO] of manifest HD) and CLOSE (<12 YEO). The CLOSE group demonstrated behavioral deficits, striatal atrophy, and reduced neural activation in the left putamen, SMA, left anterior insula and right inferior frontal gyrus. The FAR group showed reduced neural activation in the right anterior cingulate and right anterior insula. The FAR group also demonstrated increased neural activation in the left sensorimotor, left medial frontal gyrus, left precentral gyrus, bilateral superior temporal gyri and right cerebellum. The fMRI changes in the FAR group occurred in the relative absence of striatal atrophy and behavioral performance deficits. These results suggest that fMRI is sensitive to neural dysfunction occurring more than 12 years prior to the estimated onset of manifest HD. (JINS, 2007, 13, 758–769.)

Keywords

Magnetic resonance imagingBasal gangliaTime reproductionEarly detection
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 13 , Issue 5 , September 2007 , pp. 758 - 769
Copyright
2007 The International Neuropsychological Society

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References

REFERENCES

Ashburner, J. & Friston, K.J. (2000). Voxel-based morphometry: The methods. Neuroimage, 11, 805–821.Google Scholar
Ashburner, J. & Friston, K.J. (2005). Unified segmentation. Neuroimage, 26, 839–851.Google Scholar
Aylward, E.H., Brandt, J., Codori, A.M., Mangus, R.S., Barta, P.E., & Harris, G.J. (1994). Reduced basal ganglia volume associated with the gene for Huntington's disease in asymptomatic at-risk persons. Neurology, 44, 823–828.Google Scholar
Aylward, E.H., Codori, A.M., Barta, P.E., Pearlson, G.D., Harris, G.J., & Brandt, J. (1996). Basal ganglia volume and proximity to onset in presymptomatic Huntington disease. Archives of Neurology, 53, 1293–1296.Google Scholar
Aylward, E.H., Codori, A.M., Rosenblatt, A., Sherr, M., Brandt, J., Stine, O.C., Barta, P.E., Pearlson, G.D., & Ross, C.A. (2000). Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease. Movement Disorders, 15, 552–560.Google Scholar
Aylward, E.H., Sparks, B.F., Field, K.M., Yallapragada, V., Shpritz, B.D., Rosenblatt, A., Brandt, J., Gourley, L.M., Liang, K., Zhou, H., Margolis, R.L., & Ross, C.A. (2004). Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology, 63, 66–72.Google Scholar
Bartenstein, P., Weindl, A., Spiegel, S., Boecker, H., Wenzel, R., Ceballos-Baumann, A.O., Minoshima, S., & Conrad, B. (1997). Central motor processing in Huntington's disease. A PET study. Brain, 120 (Pt. 9), 1553–1567.Google Scholar
Bassett, S.S., Yousem, D.M., Cristinzio, C., Kusevic, I., Yassa, M.A., Caffo, B.S., & Zeger, S.L. (2006). Familial risk for Alzheimer's disease alters fMRI activation patterns. Brain, 129, 1229–1239.Google Scholar
Bookheimer, S.Y., Strojwas, M.H., Cohen, M.S., Saunders, A.M., Pericak-Vance, M.A., Mazziotta, J.C., & Small, G.W. (2000). Patterns of brain activation in people at risk for Alzheimer's disease. New England Journal of Medicine, 343, 450–456.Google Scholar
Brinkman, R.R., Mezei, M.M., Theilmann, J., Almqvist, E., & Hayden, M.R. (1997). The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. American Journal of Human Genetics, 60, 1202–1210.Google Scholar
Campodonico, J.R., Codori, A.M., & Brandt, J. (1996). Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation. Journal of Neurology, Neurosurgery, and Psychiatry, 61, 621–624.Google Scholar
Celone, K.A., Calhoun, V.D., Dickerson, B.C., Atri, A., Chua, E.F., Miller, S.L., DePeau, K., Rentz, D.M., Selkoe, D.J., Blacker, D., Albert, M.S., & Sperling, R.A. (2006). Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: An independent component analysis. Journal of Neuroscience, 26, 10222–10231.Google Scholar
Cox, R.W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29, 162–173.Google Scholar
Cox, R.W. & Hyde, J.S. (1997). Software tools for analysis and visualization of fMRI data. NMR in Biomedicine, 10, 171–178.Google Scholar
Davatzikos, C. (2004). Why voxel-based morphometric analysis should be used with great caution when characterizing group differences. Neuroimage, 23, 17–20.Google Scholar
DeKosky, S.T., Ikonomovic, M.D., Styren, S.D., Beckett, L., Wisniewski, S., Bennett, D.A., Cochran, E.J., Kordower, J.H., & Mufson, E.J. (2002). Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Annals of Neurology, 51, 145–155.Google Scholar
Elsinger, C.L., Rao, S.M., Zimbelman, J.L., Reynolds, N.C., Blindauer, K.A., & Hoffmann, R.G. (2003). Neural basis for impaired time reproduction in Parkinson's disease: An fMRI study. Journal of the International Neuropsychological Society, 9, 1088–1098.Google Scholar
Feigin, A., Leenders, K.L., Moeller, J.R., Missimer, J., Kuenig, G., Spetsieris, P., Antonini, A., & Eidelberg, D. (2001). Metabolic network abnormalities in early Huntington's disease: An [(18)F]FDG PET study. Journal of Nuclear Medicine, 42, 1591–1595.Google Scholar
Gauthier, L.R., Charrin, B.C., Borrell-Pages, M., Dompierre, J.P., Rangone, H., Cordelieres, F.P., De, M.J., MacDonald, M.E., Lessmann, V., Humbert, S., & Saudou, F. (2004). Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell, 118, 127–138.Google Scholar
Good, C.D., Johnsrude, I.S., Ashburner, J., Henson, R.N., Friston, K.J., & Frackowiak, R.S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage, 14, 21–36.Google Scholar
Gu, X., Li, C., Wei, W., Lo, V., Gong, S., Li, S.H., Iwasato, T., Itohara, S., Li, X.J., Mody, I., Heintz, N., & Yang, X.W. (2005). Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron, 46, 433–444.Google Scholar
Harrington, D.L., Haaland, K.Y., & Hermanowicz, N. (1998). Temporal processing in the basal ganglia. Neuropsychology, 12, 3–12.Google Scholar
Harris, G.J., Codori, A.M., Lewis, R.F., Schmidt, E., Bedi, A., & Brandt, J. (1999). Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease. Brain, 122 (Pt 9), 1667–1678.Google Scholar
Hoshi, E., Tremblay, L., Feger, J., Carras, P.L., & Strick, P.L. (2005). The cerebellum communicates with the basal ganglia. National Neuroscience, 8, 1491–1493.Google Scholar
Huntington Study Group, (1996). Unified Huntington's disease Rating Scale: Reliability and consistency. Huntington Study Group. Movement Disorders, 11, 136–142.Google Scholar
Ivry, R.B. & Keele, S.W. (1989). Timing functions of the cerebellum. Journal of Cognitive Neuroscience, 1, 134–150.Google Scholar
Kirkwood, S.C., Siemers, E., Hodes, M.E., Conneally, P.M., Christian, J.C., & Foroud, T. (2000). Subtle changes among presymptomatic carriers of the Huntington's disease gene. Journal of Neurology Neurosurgery and Psychiatry, 69, 773–779.Google Scholar
Kirkwood, S.C., Siemers, E., Stout, J.C., Hodes, M.E., Conneally, P.M., Christian, J.C., & Foroud, T. (1999). Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers. Archives of Neurology, 56, 563–568.Google Scholar
Laforet, G.A., Sapp, E., Chase, K., McIntyre, C., Boyce, F.M., Campbell, M., Cadigan, B.A., Warzecki, L., Tagle, D.A., Reddy, P.H., Cepeda, C., Calvert, C.R., Jokel, E.S., Klapstein, G.J., Ariano, M.A., Levine, M.S., DiFiglia, M., & Aronin, N. (2001). Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. Journal of Neuroscience, 21, 9112–9123.Google Scholar
Langbehn, D.R., Brinkman, R.R., Falush, D., Paulsen, J.S., & Hayden, M.R. (2004). A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clincal Genetics, 65, 267–277.Google Scholar
Lawrence, A.D., Hodges, J.R., Rosser, A.E., Kershaw, A., Ffrench-Constant, C., Rubinsztein, D.C., Robbins, T.W., & Sahakian, B.J. (1998). Evidence for specific cognitive deficits in preclinical Huntington's disease. Brain, 121 (Pt 7), 1329–1341.Google Scholar
Li, S.C., Lindenberger, U., & Sikstrom, S. (2001). Aging cognition: From neuromodulation to representation. Trends in Cognitive Science, 5, 479–486.Google Scholar
O'Boyle, D.J., Freeman, J.S., & Cody, F.W. (1996). The accuracy and precision of timing of self-paced, repetitive movements in subjects with Parkinson's disease. Brain, 119 (Pt 1), 51–70.Google Scholar
Oldfield, R.C. (1971). The assessment and analysis of handedness: The Edinburgh Inventory. Neuropsychologia, 9, 97–113.Google Scholar
Paulsen, J.S., Hayden, M., Stout, J.C., Langbehn, D.R., Aylward, E., Ross, C.A., Guttman, M., Nance, M., Kieburtz, K., Oakes, D., Shoulson, I., Kayson, E., Johnson, S.C., Penziner, E., & The Predict Investigators of the HSG (2006a). Preparing for preventive clinical trials: The Predict HD study. Archives in Neurology, 63, 883–890.Google Scholar
Paulsen, J.S., Hoth, K.F., Nehl, C., & Stierman, L. (2005). Critical periods of suicide risk in Huntington's disease. American Journal of Psychiatry, 162, 725–731.Google Scholar
Paulsen, J.S., Magnotta, V.A., Mikos, A.E., Paulson, H.L., Penziner, E., Andreasen, N.C., & Nopoulos, P.C. (2006b). Brain structure in preclinical Huntington's disease. Biological Psychiatry, 59, 57–63.Google Scholar
Paulsen, J.S., Zhao, H., Stout, J.C., Brinkman, R.R., Guttman, M., Ross, C.A., Como, P., Manning, C., Hayden, M.R., & Shoulson, I. (2001). Clinical markers of early disease in persons near onset of Huntington's disease. Neurology, 57, 658–662.Google Scholar
Paulsen, J.S., Zimbelman, J.L., Hinton, S.C., Langbehn, D.R., Leveroni, C.L., Benjamin, M.L., Reynolds, N.C., Jr., & Rao, S.M. (2004). An fMRI Biomarker of Early Neuronal Dysfunction in Presymptomatic Huntington's Disease. American Journal of Neuroradiation, 25, 1715–1721.Google Scholar
Rajah, M.N. & D'Esposito, M. (2005). Region-specific changes in prefrontal function with age: A review of PET and fMRI studies on working and episodic memory. Brain, 128, 1964–1983.Google Scholar
Rao, S.M., Harrington, D.L., Haaland, K.Y., Bobholz, J.A., Cox, R.W., & Binder, J.R. (1997). Distributed neural systems underlying the timing of movements. Journal of Neuroscience, 17, 5528–5535.Google Scholar
Rao, S.M., Mayer, A.R., & Harrington, D.L. (2001). The evolution of brain activation during temporal processing. National Neuroscience, 4, 317–323.Google Scholar
Reading, S.A., Dziorny, A.C., Peroutka, L.A., Schreiber, M., Gourley, L.M., Yallapragada, V., Rosenblatt, A., Margolis, R.L., Pekar, J.J., Pearlson, G.D., Aylward, E., Brandt, J., Bassett, S.S., & Ross, C.A. (2004). Functional brain changes in presymptomatic Huntington's disease. Annals of Neurology, 55, 879–883.Google Scholar
Reynolds, N.C.Jr., Hellman, R.S., Tikofsky, R.S., Prost, R.W., Mark, L.P., Elejalde, B.R., Lebel, R., Hamsher, K.S., Swanson, S., & Benezra, E.E. (2002). Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease. Nuclear Medicine Communications, 23, 13–18.Google Scholar
Roos, R.A., Vegter-van der Vlis, M., Hermans, J., Elshove, H.M., Moll, A.C., van de Kamp, J.J., & Bruyn, G.W. (1991). Age at onset in Huntington's disease: effect of line of inheritance and patient's sex. Journal of Medical Genetics, 28, 515–519.Google Scholar
Rosas, H.D., Hevelone, N.D., Zaleta, A.K., Greve, D.N., Salat, D.H., & Fischl, B. (2005). Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology, 65, 745–747.Google Scholar
Talairach, J. & Tournoux, P. (1988). Co-planar Stereotaxic Atlas of the Human Brain. New York: Thieme.
The Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell, 72, 971–983.Google Scholar
Thieben, M.J., Duggins, A.J., Good, C.D., Gomes, L., Mahant, N., Richards, F., McCusker, E., & Frackowiak, R.S. (2002). The distribution of structural neuropathology in pre-clinical Huntington's disease. Brain, 125, 1815–1828.Google Scholar
Tobin, A.J. & Signer, E.R. (2000). Huntington's disease: The challenge for cell biologists. Trends in Cell Biology, 10, 531–536.Google Scholar
Weeks, R.A., Ceballos-Baumann, A., Piccini, P., Boecker, H., Harding, A.E., & Brooks, D.J. (1997). Cortical control of movement in Huntington's disease. A PET activation study. Brain, 120 (Pt 9), 1569–1578.Google Scholar