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Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington’s Disease

  • Izelle Labuschagne (a1) (a2), Amy Mulick Cassidy (a3), Rachael I. Scahill (a4), Eileanoir B. Johnson (a4), Elin Rees (a4), Alison O’Regan (a1), Sarah Queller (a5), Chris Frost (a3), Blair R. Leavitt (a6), Alexandra Dürr (a7), Raymond Roos (a8), Gail Owen (a4), Beth Borowsky (a9), Sarah J. Tabrizi (a4), Julie C. Stout (a1) (a10) and the TRACK-HD Investigators...


Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)


Corresponding author

Correspondence and reprint requests to: Julie C. Stout, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia 3800. E-mail:


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Baizer, J.S., Desimone, R., & Ungerleider, L.G. (1993). Comparison of subcortical connections of inferior temporal and posterior parietal cortex in monkeys. Visual Neuroscience, 10, 5972.
Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., & Plumb, I. (2001). The “Reading the Mind in the Eyes” Test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 42, 241251.
Beiser, D.G., Hua, S.E., & Houk, J.C. (1997). Network models of the basal ganglia. Current Opinion in Neurobiology, 7, 185190.
Bethel-Fox, C.E., & Shepard, R. (1988). Mental rotation: Effects of stimulus complexity and familiarity. Journal of Experimental Psychology: Human Perception and Performance, 14, 1223.
Blankenburg, F., Ruff, C.C., Bestmann, S., Bjoertomt, O., Josephs, O., Deichmann, R., & Driver, J. (2010). Studying the role of human parietal cortex in visuospatial attention with concurrent TMS-fMRI. Cerebral Cortex, 20, 27022711.
Bogousslavsky, J., Miklossy, J., Deruaz, J.P., Assal, G., & Regli, F. (1987). Lingual and fusiform gyri in visual processing: A clinico-pathologic study of superior altitudinal hemianopia. Journal of Neurology, Neurosurgery, and Psychiatry, 50, 607614.
Deboer, L.B., Medina, J.L., Davis, M.L., Presnell, K.E., Powers, M.B., & Smits, J.A. (2013). Associations between fear of negative evaluation and eating pathology during intervention and 12-month follow-up. Cognitive Therapy and Research, 37, doi:10.1007/s10608-013-9547-y
Donner, T.H., Kettermann, A., Diesch, E., Villringer, A., & Brandt, S.A. (2003). Parietal activation during visual search in the absence of multiple distractors. Neuroreport, 14, 22572261.
Duff, K., Beglinger, L.J., Theriault, D., Allison, J., & Paulsen, J.S. (2010). Cognitive deficits in Huntington’s disease on the Repeatable Battery for the Assessment of Neuropsychological Status. Journal of Clinical and Experimental Neuropsychology, 32, 231238.
Duff, K., Paulsen, J., Mills, J., Beglinger, L.J., Moser, D.J., & Smith, M.M., . . . Coordinators of the Huntington Study Group. (2010). Mild cognitive impairment in prediagnosed Huntington disease. Neurology, 75, 500507.
Evans, D., & Rothbart, M.K. (2007). Developing a model for adult temperament. Journal of Research in Personality, 41, 868888.
Fischl, B., & Dale, A.M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences of the United States of America, 97, 1105011055.
Fischl, B., Salat, D.H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C.,&Dale, A.M. (2002). Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron, 33, 341355.
Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D.H., & Dale, A.M. (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14, 1122.
Gomez-Tortosa, E., del Barrio, A., Barroso, T., & Garcia Ruiz, P.J. (1996). Visual processing disorders in patients with Huntington’s disease and asymptomatic carriers. Journal of Neurology, 243, 286292.
Goodale, M.A., & Milner, A.D. (1992). Separate visual pathways for perception and action. Trends in Neurosciences, 15, 2025.
Hagler, D.J. Jr., Saygin, A.P., & Sereno, M. (2006). Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data. Neuroimage, 33, 10931103.
Harris, I.M., Egan, G.F., Sonkkila, C., Tochon-Danguy, H.J., Paxinos, G., & Watson, J.D. (2000). Selective right parietal lobe activation during mental rotation: A parametric PET study. Brain, 123(Pt 1), 6573.
Harris, I.M., Harris, J.A., & Caine, D. (2002). Mental-rotation deficits following damage to the right basal ganglia. Neuropsychology, 16, 524537.
Huber, P.J. (1967). The behavior of maximum likelihood estimates under nonstandard conditions, Proceedings of the Fith Berkeley Symposium on Mathematical Statistics and Probability (pp. 221233). Berkeley, CA: University of California Press.
Huntington Study Group. (1999). Unified Huntington’s Disease Rating Scale-99. Rochester, NY: Huntington Study Group.
Jacobs, H.I., Van Boxtel, M.P., Heinecke, A., Gronenschild, E.H., Backes, W.H., Ramakers, I.H.,&Verhey, F.R. (2012). Functional integration of parietal lobe activity in early Alzheimer disease. Neurology, 78, 352360.
Johnson, E.B., Rees, E.M., Labuschagne, I., Durr, A., Leavitt, B.R., Roos, R.A., & Scahill, R.I. (2015). The impact of occipital lobe cortical thickness on cognitive task performance: An investigation in Huntington’s Disease. Neuropsychologia, 79, 138146.
Klöppel, S., Gregory, S., Scheller, E., Minkova, L., Razi, A., & Durr, A., ...Track-On Investigators. (2015). Compensation in preclinical Huntington’s disease: Evidence from the Track-On study. EBioMedicine, 2, 14201429.
Kravitz, D.J., Saleem, K.S., Baker, C.I., & Mishkin, M. (2011). A new neural framework for visuospatial processing. Nature Reviews. Neuroscience, 12, 217230.
Labuschagne, I., Jones, R., Callaghan, J., Whitehead, D., Dumas, E.M., & Say, M.J., ...TRACK-HD Investigators. (2013). Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington’s disease. Psychiatry Research, 207, 118126.
Lawrence, A.D., Watkins, L.H., Sahakian, B.J., Hodges, J.R., & Robbins, T.W. (2000). Visual object and visuospatial cognition in Huntington’s disease: Implications for information processing in corticostriatal circuits. Brain, 123, 13491364.
Lineweaver, T.T., Salmon, D.P., Bondi, M.W., & Corey-Bloom, J. (2005). Differential effects of Alzheimer’s disease and Huntington’s disease on the performance of mental rotation. Journal of the International Neuropsychological Society, 11, 3039.
Mandal, P.K., Joshi, J., & Saharan, S. (2012). Visuospatial perception: An emerging biomarker for Alzheimer’s disease. Journal of Alzheimers Disease, 31(Suppl 3), S117S135.
Mohr, E., Brouwers, P., Claus, J.J., Mann, U.M., Fedio, P., & Chase, T.N. (1991). Visuospatial cognition in Huntington’s disease. Movement Disorders, 6, 127132.
Muller, C.J., & MacLehose, R.F. (2014). Estimating predicted probabilities from logistic regression: Different methods correspond to different target populations. International Journal of Epidemiology, 43, 962970.
Murray, L.L., & Stout, J.C. (1999). Discourse comprehension in Huntington’s and Parkinson’s diseases. American Journal of Speech-Language Pathology, 8, 137148.
Oehlert, G.W. (1992). A note on the delta method. The American Statistician, 46, 2729.
Penney, J.B. Jr., Vonsattel, J.P., MacDonald, M.E., Gusella, J.F., & Myers, R.H. (1997). CAG repeat number governs the development rate of pathology in Huntington’s disease. Annals of Neurology, 41, 689692.
Perry, R.J., & Hodges, J.R. (2000). Relationship between functional and neuropsychological performance in early Alzheimer disease. Alzheimer Disease and Associated Disorders, 14, 110.
Peters, M., & Battista, C. (2008). Applications of mental rotation figures of the Shepard and Metzler type and description of a mental rotation stimulus library. Brain and Cognition, 66, 260264.
Prvulovic, D., Hubl, D., Sack, A.T., Melillo, L., Maurer, K., Frolich, L., & Dierks, T. (2002). Functional imaging of visuospatial processing in Alzheimer’s disease. Neuroimage, 17, 14031414.
Robertson, I.H., Ward, T., Ridgeway, V., & Nimmo-Smith, I. (1994). The test of everday attention. Bury St. Edmunds: Thames Valley Test Company.
Robins Wahlin, T.B., Lundin, A., & Dear, K. (2007). Early cognitive deficits in Swedish gene carriers of Huntington’s disease. Neuropsychology, 21, 3144.
Rothman, K.J. (1990). No adjustments are needed for multiple comparisons. Epidemiology, 1, 4346.
Rubin, L.H., Carter, C.S., Bishop, J.R., Pournajafi-Nazarloo, H., Harris, M.S., Hill, S.K., & Sweeney, J. A. (2013). Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis. Schizophrenia Research, 146, 138143.
Shepard, R., & Metzler, J. (1971). Mental rotation of three dimensional objects. Science, 171, 701703.
Shoulson, I., & Fahn, S. (1979). Huntington disease: Clinical care and evaluation. Neurology, 29, 13.
Stout, J.C., Paulsen, J.S., Queller, S., Solomon, A.C., Whitlock, K.B., Campbell, J.C., & Aylward, E.H. (2011). Neurocognitive signs in prodromal Huntington disease. Neuropsychology, 25, 114.
Tabrizi, S.J., Langbehn, D.R., Leavitt, B.R., Roos, R.A., Durr, A., & Craufurd, D., . . . TRACK-HD Investigators. (2009). Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data. Lancet Neurology, 8, 791801.
Unschuld, P.G., Edden, R.A., Carass, A., Liu, X., Shanahan, M., Wang, X., & Ross, C.A. (2012). Brain metabolite alterations and cognitive dysfunction in early Huntington’s disease. Movement Disorders, 27, 895902.
Vonsattel, J.P., & DiFiglia, M. (1998). Huntington disease. Journal of Neuropathology and Experimental Neurology, 57, 369384.
Yeterian, E.H., & Pandya, D.N. (1995). Corticostriatal connections of extrastriate visual areas in rhesus monkeys. The Journal of Comparitive Neurology, 352, 436457.


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Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington’s Disease

  • Izelle Labuschagne (a1) (a2), Amy Mulick Cassidy (a3), Rachael I. Scahill (a4), Eileanoir B. Johnson (a4), Elin Rees (a4), Alison O’Regan (a1), Sarah Queller (a5), Chris Frost (a3), Blair R. Leavitt (a6), Alexandra Dürr (a7), Raymond Roos (a8), Gail Owen (a4), Beth Borowsky (a9), Sarah J. Tabrizi (a4), Julie C. Stout (a1) (a10) and the TRACK-HD Investigators...


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