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Huntington's disease and eyeblink classical conditioning: Normal learning but abnormal timing

Published online by Cambridge University Press:  26 February 2009

Diana S. Woodruff-Pak
Affiliation:
Department of Psychology, Temple University, Philadelphia, Pennsylvania 19122 and Laboratory of Cognitive Neuroscience, Philadelphia Geriatric Center, Philadelphia, Pennsylvania 19141
Michelle Papka
Affiliation:
Department of Psychology, Temple University, Philadelphia, Pennsylvania 19122 and Laboratory of Cognitive Neuroscience, Philadelphia Geriatric Center, Philadelphia, Pennsylvania 19141

Abstract

On the basis of what is known about the neural circuitry essential or normally involved in eyeblink classical conditioning (EBCC), the pattern of neurodegeneration in Huntington's disease (HD) would not appear to interfere with this type of learning. HD causes severe atrophy of the basal ganglia and thinning and shrinkage of the cerebral cortex. However, the hippocampus and hippocampal cholinergic system remain relatively intact, as does the cerebellum. Because the brain circuitry engaged in EBCC is neither lesioned nor disrupted in HD, it was predicted that HD patients would perform like normal control subjects in the 400-ms delay EBCC paradigm. Performance of seven patients with HD was compared to age-matched normals, with two control subjects matched to each HD patient. There were no differences in production of conditioned responses (CRs) between HD patients and normal control subjects, but the timing of the CR was abnormal in HD. Comparisons of HD patients to patients with other neurodegenerative diseases (probable Alzheimer's disease (PAD) and Down syndrome (DS) over the age of 35 with presumed Alzheimer-like neuropathology) and to patients with cerebellar lesions demonstrated significantly better EBCC performance in HD. Results suggest that the ability to acquire CRs is normal in HD, but the striatum may have some role in optimizing the timing of the CR. (JINS, 1996, 2, 323–334.)

Type
Research Article
Copyright
Copyright © The International Neuropsychological Society 1996

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References

REFERENCES

Bahro, M., Schreurs, B.G., Sunderland, T., & Molchan, S.E. (1995). The effects of scopolamine, lorazepam, and glycopyrrolate on classical conditioning of the human eyeblink response. Psychopharmacology, 122, 395400.CrossRefGoogle ScholarPubMed
Berthier, N.E. & Moore, J.W. (1986). Cerebellar Purkinje cell activity related to the classically conditioned nictitating membrane response. Experimental Brain Research, 63, 341350.CrossRefGoogle Scholar
Berthier, N.E. & Moore, J.W. (1990). Activity of deep cerebellar nuclei during classical conditioning of nictitating membrane extension in rabbit nictitating response. Experimental Brain Research, 83, 4454.CrossRefGoogle Scholar
Bollen, E., Arts, R.J.H.M., Roos, R.A.C., Van Der Valde, E.A., & Buruma, O.J.S. (1986). Brainstem reflexes and brainstem auditory evoked responses in Huntington's chorea. Journal of Neurology, Neurosurgery, and Psychiatry, 49, 313315.CrossRefGoogle ScholarPubMed
Blessed, G., Tomlinson, B.E., & Roth, M. (1968). The association between quantitative measures of dementia and of senile change in the cerebral gray matter of elderly subjects. British Journal of Psychiatry, 114, 797811.CrossRefGoogle ScholarPubMed
Buckner, R.L., Petersen, S.E., Ojemann, J.G., Miezin, F.M., Squire, L.R., & Raichle, M.E. (1995). Functional anatomical studies of explicit and implicit memory retrieval tasks. The Journal of Neuroscience, 15, 1229.CrossRefGoogle ScholarPubMed
Caraceni, T., Avanzini, G., Spreafico, R., Negri, S., Broggi, G., & Girotti, F. (1976). Study of the excitability cycle of the blink reflex in Huntington's chorea. European Neurology, 14, 465472.CrossRefGoogle ScholarPubMed
Clark, R.E., Zhang, A.A., & Lavond, D.G. (1992). Reversible lesions of the cerebellar interpositus nucleus during acquisition and retention of a classically conditioned behavior. Behavioral Neuroscience, 106, 879888.CrossRefGoogle ScholarPubMed
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum.Google Scholar
Daum, I., Channon, S., & Canavan, A.G.M. (1989). Classical conditioning in patients with severe memory problems. Journal of Neurology, Neurosurgery, and Psychiatry, 52,4751.CrossRefGoogle ScholarPubMed
Daum, I., Channon, S., Polkey, C.E., & Gray, J.A. (1991). Classical conditioning after temporal lobe lesions in man: Impairment in conditional discrimination. Behavioral Neuroscience, 105, 396408.CrossRefGoogle ScholarPubMed
Daum, I., Schugens, M.M., Ackermann, H., Lutzenberger, W., Dichgans, J., & Birbaumer, N. (1993). Classical conditioning after cerebellar lesions in humans. Behavioral Neuroscience, 107, 748756.CrossRefGoogle ScholarPubMed
Esteban, A., Mateo, D., & Giminez-Roldan, S. (1981). Early detection of Huntington's disease: Blink reflex and levodopa load in presymptomatic and incipient subjects. Journal of Neurology, Neurosurgery, and Psychiatry, 44, 4348.CrossRefGoogle ScholarPubMed
Gormezano, I. (1966). Classical conditioning. In Sidowski, J.B. (Ed)., Experimental methods and instrumentation in psychology (pp. 385420). New York: McGraw-Hill.Google Scholar
Gould, T.J. & Steinmetz, J.E. (1994). Multiple-unit activity from rabbit cerebellar cortex and interpositus nucleus during classical discrimination/reversal eyelid conditioning. Brain Research, 652, 98106.CrossRefGoogle ScholarPubMed
Grafton, S.T., Mazziotta, J.C., Presty, S., Friston, K.J., Frackowiak, R.S.J., & Phelps, M.E. (1992). Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET. Journal of Neuroscience, 12, 25422548.CrossRefGoogle ScholarPubMed
Harvey, J.A. & Gormezano, I. (1981). Effects of haloperidol and pimozide on classical conditioning of the rabbit nictitating membrane response. Journal of Pharmacology and Experimental Therapy, 218,712719.Google ScholarPubMed
Harvey, J.A., Gormezano, I., & Cool-Hauser, V.A. (1983). Effects of scopolamine and methylscopolaminc on classical conditioning of the rabbit nictitating membrane response. Journal of Pharmacology and Experimental Therapeutics, 225,4249.Google ScholarPubMed
Heindel, W.C., Salmon, D.P., Shults, C.W., Walicke, P.A., & Butters, N. (1989). Neuropsychological evidence for multiple implicit memory systems: A comparison of Alzheimer's, Huntington's, and Parkinson's disease patients. The Journal of Neuroscience, 9, 582587.CrossRefGoogle ScholarPubMed
Ivry, R. & Keele, S.W. (1989). Timing functions of the cerebellum. Cognitive Neuroscience, 1, 134150.Google ScholarPubMed
Kao, K.-T. & Powell, D.A. (1988). Lesions of the substantia nigra retard Pavlovian eye-blink but not heart rate conditioning in the rabbit. Behavioral Neuroscience, 102, 515525.CrossRefGoogle Scholar
Keane, M.M., Gabrieli, J.D.E., Fennema, A.C., Growdon, J.H., & Corkin, S. (1991). Evidence for a dissociation between perceptual and conceptual priming in Alzheimer's disease. Behavioral Neuroscience, 105, 326342.CrossRefGoogle ScholarPubMed
Krupa, D.J., Thompson, J.K., & Thompson, R.F. (1993). Localization of a memory trace in the mammalian brain. Science, 260, 989991.CrossRefGoogle ScholarPubMed
Lavond, D.G., Hembree, T.L., & Thompson, R.F. (1985). Effect of kainic acid lesions of the cerebellar interpositus nucleus on eyelid conditioning in the rabbit. Brain Research, 326, 179182.CrossRefGoogle ScholarPubMed
Lavond, D.G. & Steinmetz, J.E. (1989). Acquisition of classical conditioning without cerebellar cortex. Behavioural Brain Research, 33, 113164.CrossRefGoogle ScholarPubMed
Lincoln, J.S., McCormick, D.A., & Thompson, R.F. (1982). Ipsilateral cerebellar lesions prevent learning of the classically conditioned nictitating membrane/eyelid response. Brain Research, 242, 190193.CrossRefGoogle ScholarPubMed
Logan, C.G. & Grafton, S.T. (1995). Functional anatomy of human eyeblink conditioning determined with regional cerebral glucose metabolism and positron emission tomography. Proceedings of the National Academy of Science USA, 92, 75007504.CrossRefGoogle ScholarPubMed
Lye, R.H., O'Boyle, D.J., Ramsden, R.T., & Schady, W. (1988). Effects of a unilateral cerebellar lesion on the acquisition of eye-blink conditioning in man. Journal of Physiology (London), 403, 58P.Google Scholar
McCormick, D.A., Lavond, D.G., Clark, G.A., Kettner, R.E., Rising, C.E., & Thompson, R.F. (1981). The engram found? Role of the cerebellum in classical conditioning of nictitating membrane and eyelid responses. Bulletin of the Psychonomic Society, 18, 103105.CrossRefGoogle Scholar
McCormick, D.A. & Thompson, R.F. (1984a). Cerebellum: Essential involvement in the classically conditioned eyelid response. Science, 223, 296299.CrossRefGoogle ScholarPubMed
McCormick, D.A. & Thompson, R.F. (1984b). Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. Journal of Neuroscience, 4, 28112822.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E.M. (1984). Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34, 939944.CrossRefGoogle ScholarPubMed
Molchan, S.E., Sunderland, T., Mclntosh, A.R., Herscovitch, P., & Schreurs, B.G. (1994). A functional anatomical study of associative learning in humans. Proceedings of the National Academy of Science USA, 91, 81228126.CrossRefGoogle ScholarPubMed
Moore, J.W., Goodell, N.A., & Solomon, P.R. (1976). Central cholinergic blockade by scopolamine and habituation, classical conditioning, and latent inhibition of the rabbit's nictitating membrane response. Physiological Psychology, 4, 395399.CrossRefGoogle Scholar
Perrett, S., Ruiz, B., & Mauk, M. (1993). Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. Journal of Neuroscience, 13, 17081718.CrossRefGoogle ScholarPubMed
Port, R.L., Romano, A.G., Steinmetz, J.E., Mikhail, A.A., & Patterson, M.M. (1986). Retention and acquisition of classical trace conditioned responses by rabbits with hippocampal lesions. Behavioral Neuroscience, 100, 745752.CrossRefGoogle ScholarPubMed
Powell, D.A., Mankowski, D., & Buchanan, S. (1978). Concomitant heart rate and corneoretinal potential conditioning in the rabbit (Oryctolagus cuniculus): Effects of caudate lesions. Physiology and Behavior, 20, 143150.CrossRefGoogle ScholarPubMed
Salmon, D.P., Shimamura, A.P., Butters, N., & Smith, S. (1988). Lexical and semantic priming deficits in patients with Alzheimer's disease. Journal of Clinical and Experimental Neuropsychology, 10, 477494.CrossRefGoogle ScholarPubMed
Schmaltz, L.W. & Theios, J. (1972). Acquisition and extinction of a classically conditioned response in hippocampectomizcd rabbits (Oryctolagus cuniculus). Journal of Comparative and Physiological Psychology, 79, 328333.CrossRefGoogle ScholarPubMed
Sears, L.L., Finn, P.R., & Steinmetz, J.E. (1994). Abnormal classical eyeblink conditioning in autism. Journal of Autism and Developmental Disorders, 24, 737751.CrossRefGoogle ScholarPubMed
Sears, L.L., & Steinmetz, J.E. (1990). Haloperidol impairs classically conditioned nictitating membrane responses and conditioning- related cerebellar interpositus nucleus activity in rabbits. Pharmacology, Biochemistry and Behavior, 36, 821830.CrossRefGoogle ScholarPubMed
Shimamura, A.P., Salmon, D.P., Squire, L.R., & Butters, N. (1987). Memory dysfunction and word priming in dementia and amnesia. Behavioral Neuroscience, 101, 347351.CrossRefGoogle ScholarPubMed
Solomon, P.R., Groccia-Ellison, M., Flynn, D., Mirak, J., Edwards, K.R., Dunehew, A., & Stanton, M.E. (1993). Disruption of human eyeblink conditioning after central cholinergic blockade with scopolamine. Behavioral Neuroscience, 107, 271279.CrossRefGoogle ScholarPubMed
Solomon, P.R., Levine, E., Bein, T., & Pendlebury, W.W. (1991). Disruption of classical conditioning in patients with Alzheimer's disease. Neurobiology of Aging, 12, 283287.CrossRefGoogle ScholarPubMed
Solomon, P.R. & Moore, J.W. (1975). Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablations. Journal of Comparative and Physiological Psychology, 89, 11921203.CrossRefGoogle Scholar
Solomon, P.R., Solomon, S.D., Vander, SchaafE., & Perry, H.E. (1983). Altered activity in the hippocampus is more detrimental to classical conditioning than removing the structure. Science, 220, 329331.CrossRefGoogle ScholarPubMed
Solomon, P.R., Stowe, G.T., & Pendlebury, W.W. (1989). Disrupted eyelid conditioning in a patient with damage to cerebellar afferents. Behavioral Neuroscience, 103, 898902.CrossRefGoogle Scholar
Solomon, P.R., Vander, SchaafE.R., Weisz, D.J., & Thompson, R.F. (1986). Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response. Behavioral Neuroscience, 100,729744.CrossRefGoogle ScholarPubMed
Squire, L.R. (1992). Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychological Review, 99, 195231.CrossRefGoogle ScholarPubMed
Steinmetz, J.E., Lavond, D.G., Ivkovich, D., Logan, C.G., & Thompson, R.F. (1992). Disruption of classical eyelid conditioning after cerebellar lesions: Damage to a memory trace system or a simple performance deficit? The Journal of Neuroscience, 12, 44034426.CrossRefGoogle ScholarPubMed
Thompson, R.F. (1986). The neurobiology of learning and memory. Science, 233, 941947.CrossRefGoogle ScholarPubMed
Thompson, R.F. (1990). Neural mechanisms of classical conditioning in mammals. Philosophical Transactions of the Royal Society of London, 319, 161170.Google Scholar
Topka, H., Valls-Sole, J., Massaquoi, S.G., & Hallett, M. (1993). Deficit in classical conditioning in patients with cerebellar degeneration. Brain, 116, 961969.CrossRefGoogle ScholarPubMed
Weiskrantz, L. & Warrington, E.K. (1979). Conditioning in amnesic patients. Neuropsychologia, 17, 187194.CrossRefGoogle ScholarPubMed
White, I.M., Miller, D.P., White, W., Dike, G.L., Rebec, G.V., & Steinmetz, J.E. (1994). Neuronal activity in rabbit neostriatum during classical eyelid conditioning. Experimental Brain Research, 99, 179190.CrossRefGoogle ScholarPubMed
Woodruff-Pak, D.S. (1993). Eyeblink classical conditioning in H.M.: Delay and trace paradigms. Behavioral Neuroscience, 107, 911925.CrossRefGoogle ScholarPubMed
Woodruff-Pak, D.S., Cronholm, J.F., & Sheffield, J.B. (1990a). Purkinje cell number related to rate of eyeblink classical conditioning. NeuroReport, 1, 165168.CrossRefGoogle Scholar
Woodruff-Pak, D.S., Finkbiner, R.G., & Sasse, D.K. (1990b). Eyeblink classical conditioning discriminates Alzheimer's patients from non-demented aged. NeuroReport, 1, 4549.CrossRefGoogle ScholarPubMed
Woodruff-Pak, D.S., Papka, M., & Simon, E.W. (1994). Eyeblink classical conditioning in Down's syndrome, fragile X syndrome, and normal adults over and under age 35. Neuropsychology, 8, 1424.CrossRefGoogle Scholar
Woodruff-Pak, D.S., Romano, S., Papka, M., Ivry, R.B. (in press, a). Cerebellar involvement in eyeblink classical conditioning in humans. Neuropsychology.Google Scholar
Woodruff-Pak, D.S., Papka, M., Romano, S., & Li, Y.-T. (in press, b). Eyeblink classical conditioning in Alzheimer's disease and cerebrovascular dementia. Neurobiology of Aging.Google Scholar
Woodruff-Pak, D.S., Romano, S., & Papka, M. (1996). Training to criterion in eyeblink classical conditioning in Alzheimer's disease, Down's syndrome with Alzheimer's disease, and normal age-matched elderly. Behavioral Neuroscience, 110, 2229.CrossRefGoogle Scholar
Woodruff-Pak, D.S. & Thompson, R.F. (1988). Classical conditioning of the eyelid response in the delay paradigm in adults aged 18–83 years. Psychology and Aging, 3, 219229.CrossRefGoogle ScholarPubMed
Yates, C.M., Simpson, J., Maloney, A.F.J., Gordon, A., & Reid, A.H. (1980). Alzheimer-like cholinergic deficiency in Down syndrome. The Lancet, 2, 979.CrossRefGoogle ScholarPubMed
Yeo, C.H., Hardiman, M.J., & Glickstein, M. (1985). Classical conditioning of the nictitating membrane response of the rabbit. 1. Lesions of the cerebellar nuclei. Experimental Brain Research, 60, 8798.CrossRefGoogle ScholarPubMed
Zeffiro, T.A., Blaxton, T., Gabrieli, J., Bookheimer, S.Y., Carrillo, M., Binion, E., Disterhoft, J., & Theodore, W. (1993). Regional cerebral blood flow changes during classical eyeblink conditioning in man. Society for Neuroscience Abstracts, 19, 1078.Google Scholar