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Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: A structural MRI study

Published online by Cambridge University Press:  25 February 2003

Murphy Claire ,
Jernigan Terry L.  and
Fennema-Notestine Christine
Murphy Claire*
Affiliation:
San Diego State University, San Diego, California UCSD School of Medicine, La Jolla, California
Jernigan Terry L.
Affiliation:
SDVAHS San Diego, California UCSD School of Medicine, La Jolla, California
Fennema-Notestine Christine
Affiliation:
SDVAHS San Diego, California UCSD School of Medicine, La Jolla, California
*
Reprint requests to: Dr. Claire Murphy, SDSU/UCSD Joint Doctoral Program, 6363 Alvarado Ct., Suite 101, San Diego, CA 92120-4913. E-mail: cmurphy@sunstroke.sdsu.edu
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Abstract

The very high sensitivity and specificity of odor identification tasks in discriminating between Alzheimer's patients and normals suggests that they reflect the presence of underlying neuropathology. Significant neuropathological changes are seen in areas critical to processing olfactory information, even in the early stages of Alzheimer's disease (AD). The current study was designed to investigate whether performance on olfactory tasks (odor threshold and odor identification) was related to volumetric MRI measures of mesial temporal areas central to olfactory information processing and important in the neuropathology of AD. Participants were 8 male and 5 female patients with probable AD, and 10 male and 12 female normal age-matched controls, diagnosed at the UCSD Alzheimer's Disease Research Center. The study investigated correlations between volumetric measures of hippocampus, the parahippocampal gyrus and the amygdala, and the psychophysical measures of olfactory function. Robust relationships were observed between mesial temporal lobe volumes and olfactory functional measures. The finding of a strong relationship between left hippocampal volume and performance on the odor identification task (r = .85) is compatible with a left-hemisphere superiority for verbally mediated olfactory tasks. The findings suggest a neural substrate for the breakdown in functional performance on verbally mediated odor identification tasks in Alzheimer's disease and suggest the utility of quantitative MRI measures and psychophysical performance in the assessment of AD. These results support the potential clinical utility of inclusion of odor identification tests in diagnostic batteries for detecting AD. (JINS, 2003, 9, 459–471.)

Keywords

MRIOlfactionMesial temporal lobeAmygdalaParahippocampal gyrus
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 9 , Issue 3 , 25 March 2003 , pp. 459 - 471
Copyright
Copyright © The International Neuropsychological Society 2003

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References

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (Rev. 3rd ed.). Washington, DC: Author.Google Scholar
Andreasen, N.C., Arndt, S., Swayze, V., Cizadlo, T., Flaum, M., O'Leary, D., Ehrhardt, J.C., & Yuh, W.T. (1994). Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science, 266, 294–298.10.1126/science.7939669CrossRefGoogle Scholar
Bacon, A.W., Bondi, M.W., Salmon, D.P., & Murphy, C. (1998). Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction. Annals of the New York Academy of Sciences, 855, 723–731.10.1111/j.1749-6632.1998.tb10651.xCrossRefGoogle Scholar
Bacon, A.W., Paulsen, J.S., & Murphy, C. (1999). A test of odor fluency in patients with Alzheimer's disease and Huntington's Chorea. Journal of Clinical and Experimental Neuropsychology, 21, 341–351.CrossRefGoogle Scholar
Biella, G. & de Curtis, M. (2000). Olfactory inputs activate the medial entorhinal cortex via the hippocampus. Journal of Neurophysiology, 83, 1924–1931.10.1152/jn.2000.83.4.1924CrossRefGoogle Scholar
Braak, H., Braak, E. (1992). The human entorhinal cortex: Normal morphology and lamina-specific pathology in various diseases. Neuroscience Research, 15, 6–31.10.1016/0168-0102(92)90014-4CrossRefGoogle Scholar
Braak, H., Braak, E. (1994). Morphological criteria for the recognition of Alzheimer's disease and the distribution pattern of cortical changes related to this disorder. Neurobiology of Aging, 15, 355–356.10.1016/0197-4580(94)90032-9CrossRefGoogle Scholar
Braak, H., Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18, 351–357.10.1016/S0197-4580(97)00056-0CrossRefGoogle Scholar
Cahn, D., Sullivan, E.V., Shear, P.K., Marsh, L., Fama, R., Lim, K.L., Yesavage, J.A., Tinklenberg, J.R., & Pfefferbaum, A. (1998). Structural MRI correlates of recognition memory in Alzheimer's disease. Journal of the International Neuropsychological Society, 4, 106–114.10.1017/S1355617798001064CrossRefGoogle Scholar
Carmichael, S.T., Clugnet, M.C., & Price, J.L. (1994). Central olfactory connections in the macaque monkey. Journal of Comparative Neurology, 346, 403–434.CrossRefGoogle Scholar
Cerf-Ducastel, B. & Murphy, C. (2001). FMRI activation in response to odorants orally delivered in aqueous solution. Chemical Senses, 26, 625–637.CrossRefGoogle Scholar
Cohen, N.J., Ryan, J., Hunt, C., Romine, L., Wszalek, T., & Nash, C. (1999). Hippocampal system and declarative (relational) memory: Summarizing the data from functional neuroimaging studies. Hippocampus, 9, 83–98.3.0.CO;2-7>CrossRef3.0.CO;2-7>Google Scholar
Delis, D.C., Kramer, J.H., Kaplan, E., & Ober, B.A. (1987). The California Verbal Learning Test. New York: The Psychological Corporation.Google Scholar
Deweer, B., Lehericy, S., Pillon, B., Baulac, M., Chiras, J., Marsault, C., Agid, & Y., Dubois. B. (1995). Memory disorders in probable Alzheimer's disease: The role of hippocampal atrophy as shown with MRI. Journal of Neurology, Neurosurgery, and Psychiatry, 58, 590–597.CrossRefGoogle Scholar
Doty, R.L., Reyes, P.F., & Gregor, T. (1987). Presence of both identification and detection deficits in Alzheimer's disease. Brain Research Bulletin, 18, 597–600.CrossRefGoogle Scholar
Doty, R.L., Shaman, P., & Dann, M. (1984). Development of the University of Pennsylvania Smell Identification Test: A standardized microencapsulated test of olfactory function. Physiology and Behavior, 32, 489–502.10.1016/0031-9384(84)90269-5CrossRefGoogle Scholar
Eichenbaum, H. (1998). Using olfaction to study memory. Annals of the New York Academy of Sciences, 855, 657–669.10.1111/j.1749-6632.1998.tb10642.xCrossRefGoogle Scholar
Ekman, G., Berglund, B., Berglund, U., & Lindvall, T. (1967). Perceived intensity of odor as a function of time of adaptation. Scandinavian Journal of Psychology, 8, 177–186.CrossRefGoogle Scholar
Eskenazi, B., Cain, W.S., Novelly, R.A., & Mattson, R. (1986). Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia, 24, 553–562.10.1016/0028-3932(86)90099-0CrossRefGoogle Scholar
Fama, R., Sullivan, E.V., Shear, P.K., Marsh, L., Yesavage, J.A., Tinklenberg, J.R., Lim, K.O., & Pfefferbaum, A. (1997). Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease. Archives of Neurology, 43, 719–728.CrossRefGoogle Scholar
Fennema-Notestine, C., Archibald, S.L., Jernigan, T.L., & Thal, L. (1997). Quantitative MRI in Alzheimer's disease and controls with and without the apolipoprotein E e4 allele. Society for Neuroscience Abstracts, 23, 2173.Google Scholar
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-Mental State”: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle Scholar
Hubbard, B.M. & Anderson, J.M. (1981). A quantitative study of cerebral atrophy in old age and senile dementia. Journal of the Neurological Sciences, 50, 135–145.10.1016/0022-510X(81)90048-4CrossRefGoogle Scholar
Jack, C.R., Petersen, R.C., Xy, Y., O'Brien, P.C., Smith, G.E., Ivnik, R.J., Tangalos, E.G., & Kokmen, E. (1998). Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology, 51, 993–999.CrossRefGoogle Scholar
Jernigan, T.L., Press, G.A., & Hesselink, J.R. (1990). Methods for measuring brain morphologic features on magnetic resonance images: Validation and normal aging. Archives of Neurology, 47, 27–32.CrossRefGoogle Scholar
Jernigan, T.L., Archibald, S.L., Berhow, M.T., Sowell, E.R., Foster, D.S., & Hesselink, J.R. (1991a). Cerebral structure on MRI, Part I: Localization of age-related changes. Biological Psychiatry, 29, 55–67.CrossRefGoogle Scholar
Jernigan, T.L., Salmon, D.P., Butters, N., & Hesselink, J.R. (1991b). Cerebral structure on MRI, Part II: Specific changes in Alzheimer's and Huntington's diseases. Biological Psychiatry, 29, 68–81.10.1016/0006-3223(91)90211-4CrossRefGoogle Scholar
Jernigan, T.L. & Ostergaard, A.L. (1993). Word priming and recognition memory are both affected by mesial temporal lobe damage. Neuropsychology, 7, 14–26.10.1037/0894-4105.7.1.14CrossRefGoogle Scholar
Jernigan, T.L., Ostergaard, A.L., & Fennema-Notestine, C. (2001a). Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory. Journal of the International Neuropsychological Society, 7, 63–78.10.1017/S1355617701711071CrossRefGoogle Scholar
Jernigan, T.L., Archibald, S.L., Fennema-Notestine, C., Gamst, A., Stout, J.C., Bonner, J., & Hesselink, J. (2001b). Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiology of Aging, 22, 581–594.CrossRefGoogle Scholar
Jones-Gotman, M. & Zatorre, R.J. (1993). Odor recognition memory in humans: role of right temporal and orbitofrontal regions. Brain and Cognition, 22, 182–198.10.1006/brcg.1993.1033CrossRefGoogle Scholar
Kaplan, E., Goodglass, H., & Weintraub, S. (1983). The Boston Naming Test. Philadelphia: Lea & Febiger.Google Scholar
Kesslak, J.P., Nalcioglu, O., & Cotman, C. (1991). Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease. Neurology, 41, 51–54.CrossRefGoogle Scholar
Kettenmann, B., Hummel, C., Stefan, H., & Kobal, G. (1997). Multiple olfactory activity in the human neocortex identified by magnetic source imaging. Chemical Senses, 22, 493–502.CrossRefGoogle Scholar
Knupfer, L. & Spiegel, R. (1986). Differences in olfactory test performance between normal aged, Alzheimer and vascular type dementia individuals. International Journal of Geriatric Psychiatry, 1, 3–14.10.1002/gps.930010103CrossRefGoogle Scholar
Koss, E. (1986). Olfactory dysfunction in Alzheimer's disease. Developmental Neuropsychology, 2, 89–99.10.1080/87565648609540332CrossRefGoogle Scholar
Levy, L.M., Henkin, R.I., Hutter, A., Lin, C.S., Martins, D., & Schellinger, D. (1997). Functional MRI of human olfaction. Journal of Computer Assisted Tomography, 21, 849–856.10.1097/00004728-199711000-00002CrossRefGoogle Scholar
Lorig, T.S., Elmes, D.G., Zald, D.H., & Pardo, J.V. (1999). A computer-controlled olfactometer for fMRI and electrophysiological studies of olfaction. Behavior Research Methods, Instruments, and Computers, 31, 370–375.CrossRefGoogle Scholar
Martin, A. (1999). Automatic activation of the medial temporal lobe during encoding: Lateralized influences of meaning and novelty. Hippocampus, 9, 62–70.10.1002/(SICI)1098-1063(1999)9:1<62::AID-HIPO7>3.0.CO;2-K3.0.CO;2-K>CrossRefGoogle Scholar
Mattis, S. (1976). Mental status examination for organic mental syndrome in the elderly patient. In L. Bellak & T.B. Katasu (Eds.), Geriatric psychiatry: A handbook for psychiatrists and primary care physicians (pp. 77–121). New York: Grune & Statton.Google Scholar
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 Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.10.1212/WNL.34.7.939CrossRefGoogle Scholar
Morgan, C.D., Covington, J.W., Geisler, M.W., Polich, J., & Murphy, C. (1997). Olfactory event-related potentials: Older males demonstrate the greatest deficits. Electroencephalography and Clinical Neurophysiology, 104, 351–358.10.1016/S0168-5597(97)00020-8CrossRefGoogle Scholar
Morgan, C., Geisler, M.W., Covington, J.W., Polich, J., & Murphy, C. (1999). Olfactory P3 in young and older adults. Psychophysiology, 36, 281–287.10.1017/S0048577299980265CrossRefGoogle Scholar
Morgan, C.D. & Murphy, C. (2002). Olfactory event-related potentials in Alzheimer's disease. Journal of the International Neuropsychological Society, 753–763.CrossRefGoogle Scholar
Morgan, C.D., Nordin, S., & Murphy, C. (1995). Odor identification as an early marker for Alzheimer's disease: Impact of lexical functioning and detection sensitivity. Journal of Clinical and Experimental Neuropsychology, 17, 793–803.10.1080/01688639508405168CrossRefGoogle Scholar
Murphy, C. (1983). Age-related changes in the threshold, psychophysical function and pleasantness of menthol. Journal of Gerontology, 38, 217–222.CrossRefGoogle Scholar
Murphy, C. (1993). Senescence and clinical changes in the olfactory system: Psychophysical considerations. In Development, growth and senescence in the chemical senses (pp. 153–160). Bethesda, MD: NIH Publication No. 93-3483.Google Scholar
Murphy, C. (1999). Loss of olfactory function in dementing disease. Physiology and Behavior, 66, 177–182.CrossRefGoogle Scholar
Murphy, C., Anderson, J., & Markinson, S. (1994a). Psychophysical assessment of chemosensory disorders in clinical populations. In K. Kurihara, N. Suzuki, & H. Ogawa (Eds.), Olfaction and taste, XI, (pp. 609–613). New York: Springer-Verlag.10.1007/978-4-431-68355-1_251CrossRefGoogle Scholar
Murphy, C., Bacon, A.W., Bondi, M.W., & Salmon, D.P. (1998). Apolipoprotein E status is associated with odor identification deficits in non-demented older persons. Annals of the New York Academy of Sciences, 855, 744–750.CrossRefGoogle Scholar
Murphy, C., Cain, W.S., Gilmore, M.M., & Skinner, B. (1991). Sensory and semantic factors in recognition memory for odors and graphic stimuli: Elderly versus young persons. American Journal of Psychology, 104, 161–192.CrossRefGoogle Scholar
Murphy, C., Gilmore, M.M., Seery, C.S., Salmon, D.P., & Lasker, B.P. (1990). Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiology of Aging, 11, 465–469.CrossRefGoogle Scholar
Murphy, C., Lasker, B.R., & Salmon, D.P. (1987). Olfactory dysfunction and odor memory in Alzheimer's disease, Huntington's disease and normal aging. Society for Neuroscience Abstracts, 13, 1403.Google Scholar
Murphy, C. & Morgan, C.D. (2001). Olfactory function and event-related potentials in Alzheimer's disease. In K. Iqbal, S.S. Sisodia, & B. Winglad (Eds.), Alzheimer's disease: Advances in etiology, pathogensis and therapeutics (pp. 237–251). London: Wiley.Google Scholar
Murphy, C., Morgan, C.D., Geisler, M.W., Wetter, S., Covington, J.W., Madowitz, M.D., Nordin, S., & Polich, J. (2000). Olfactory event-related potentials and aging: Normative data. International Journal of Psychophysiology, 36, 133–145.CrossRefGoogle Scholar
Murphy, C., Nordin, S., & Acosta, L. (1997). Odor learning, recall and recognition memory in young and elderly adults. Neuropsychology, 11, 126–137.CrossRefGoogle Scholar
Murphy, C., Nordin, S., de Wijk, R.A., Cain, W.S., & Polich, J. (1994b). Olfactory-evoked potentials: Assessment of young and elderly, and comparison to psychophysical threshold. Chemical Senses, 19, 47–56.CrossRefGoogle Scholar
Niccoli-Waller, C.A., Harvey, J., Nordin, S., & Murphy, C. (1999). Deficit in remote odor memory as measured by familiarity in Alzheimer's disease. Journal of Adult Development, 6, 131–136.CrossRefGoogle Scholar
Nordin, S., Monsch, A., & Murphy, C. (1995). Unawareness of smell loss in normal aging and Alzheimer's disease: Discrepancy between self-reported and diagnosed smell sensitivity, Journal of Gerontology, 50B, P187–P192.CrossRefGoogle Scholar
Nordin, S. & Murphy, C. (1996). Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease. Neuropsychology, 10, 112–119.CrossRefGoogle Scholar
Nyberg, L., McIntosh, A.R., Houle, S., Nilsson, L.G., & Tulving, E. (1996). Activation of medial temporal structures during episodic encoding. Nature, 380, 715–717.CrossRefGoogle Scholar
O'Donnell, B.F., Friedman, S., Swearer, J.M., & Drachman, D. (1992). Active and passive P300 latency and psychometric performance: influence of age and individual differences. International Journal of Psychophysiology, 12, 187–195.Google Scholar
Ohm, T.G. & Braak, H. (1987). Olfactory bulb changes in Alzheimer's disease. Acta Neuropathologica (Berlin), 73, 365–369.10.1007/BF00688261CrossRefGoogle Scholar
Petersen, R.C., Jack, C.R., Xu, Y.-C., Waring, S.C., O'Brien, P.C., Smith, G.E., Ivnik, R.J., Tangalos, E.G., Boeve, B.F., & Kokmen, E. (2000). Memory and MRI-based hippocampal volumes in aging and AD. Neurology, 54, 581–587.10.1212/WNL.54.3.581CrossRefGoogle Scholar
Price, J.L. (1985). Beyond the primary olfactory cortex: Olfactory-related areas in the neocortex, thalamus and hypothalamus. Chemical Senses, 10, 239–258.CrossRefGoogle Scholar
Price, J.L. (1987). The central olfactory and accessory olfactory systems. In T.E. Finger & W.L. Silver (Eds.), Neurobiology of taste and smell (pp. 179–203). New York: Wiley.Google Scholar
Price, J.L., Davis, P.B., Morris, J.C., & White, D.L. (1991). The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiology of Aging, 12, 295–312.CrossRefGoogle Scholar
Raz, N., Raz, S., Yeo, R.A., Turkheimer, E., Bigler, E.D., & Cullum, C.M. (1987). Relationship between cognitive and morphological asymmetry in dementia of the Alzheimer type: A CT scan study. International Journal of Neuroscience, 35, 225–232.CrossRefGoogle Scholar
Rombouts, S.A.R.B., Barkhof, F., Witter, M.P., & Scheltens, P. (2000). Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease. Neuroscience Letters, 285, 231–233.10.1016/S0304-3940(00)01067-3CrossRefGoogle Scholar
Royet, J.P., Koenig, O., Gregoire, M.C., Cinotti, L., Lavenne, F., Le Bars, D., Costes, N., Vigouroux, M., Farget, V., Sicard, G., Holley, A., Mauguiere, F., Comar, D., & Froment, J.C. (1999). Functional anatomy of perceptual and semantic processing for odors. Journal of Cognitive Neuroscience, 11, 94–109.CrossRefGoogle Scholar
Savic, I. & Berglund, H. (2000). Right-nostril dominance in discrimination of unfamiliar, but not familiar odours. Chemical Senses, 25, 517–523.CrossRefGoogle Scholar
Savic, I., Gulyas, B., Larsson, M., & Roland, P. (2000). Olfactory functions are mediated by parallel and hierarchical processing. Neuron, 26, 735–745.CrossRefGoogle Scholar
Schiffman, S.S. (1997). Taste and smell losses in normal aging and disease. Journal of the American Medical Association, 278, 1357–1362.10.1001/jama.1997.03550160077042CrossRefGoogle Scholar
Serby, M., Corwin, J., Novatt, A., Conrad, P., & Rotrosen, J. (1985). Olfaction in dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 48, 848–849.CrossRefGoogle Scholar
Small, D.M., Jones-Gotman, M., Zatorre, R.J., Petrides, M., & Evans, A.C. (1997). Flavor processing: More than the sum of its parts. Neuroreport, 8, 3913–3917.CrossRefGoogle Scholar
Sobel, N., Prabhakaran, V., Zhao, Z., Desmond, J.E., Glover, G.H., Sullivan, E.V., & Gabrieli, J.D. (2000). Time course of odorant-induced activation in the human primary olfactory cortex. Journal of Neurophysiology, 83, 537–551.CrossRefGoogle Scholar
Sowell, E.R., Thompson, P.M., Holmes, C.J., Batth, R., Jernigan, T.L., & Toga, A. (1999a). Localizing age-related changes in brain structure between childhood and adolescence using Statistical Parametric Mapping. NeuroImage, 9, 587–597.CrossRefGoogle Scholar
Sowell, E.R., Thompson, P.M., Holmes, C.J., Jernigan, T.L., & Toga, A.W. (1999b). In vivo evidence for post-adolescent brain maturation in frontal and striatal regions [Letter to the editor]. Nature Neuroscience, 2, 859–861.CrossRefGoogle Scholar
Squire, L.R. (1992). Declarative and nondeclarative memory: Multiple brain systems supporting learning and memory. Journal of Cognitive Neuroscience, 4, 232–242.CrossRefGoogle Scholar
Stout, J.C., Jernigan T.L., & Archibald S.L., Salmon D.P. (1996). Association of dementia severity with cortical grey matter and abnormal white matter volumes in dementia of the Alzheimer type. Archives of Neurology, 53, 742–749.CrossRefGoogle Scholar
Stout, J.C., Bondi, M.W., Jernigan, T.L., Archibald, S.L., Delis, D.C., & Salmon, D.P. (1999). Regional cerebral volume loss associated with verbal learning and memory in dementia of the Alzheimer Type. Neuropsychology, 13, 188–197.CrossRefGoogle Scholar
Thesen, T. & Murphy, C. (2001). Age-related changes in olfactory processing detected with olfactory event-related brain potentials using velopharyngeal closure and natural breathing. International Journal of Psychophysiology, 40, 19–27.CrossRefGoogle Scholar
Toledo-Morrell, L., Dickerson, G., Sullivan, M.P., Spanovic, C., Wilson, R., & Bennett, D.A. (2000). Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease. Hippocampus, 10, 136–142.10.1002/(SICI)1098-1063(2000)10:2<136::AID-HIPO2>3.0.CO;2-J3.0.CO;2-J>CrossRefGoogle Scholar
Tulving, E., Habib, R., Nyberg, L., Lepage, M., & McIntosh, A.R. (1999). Positron emission tomography correlations in and beyond medial temporal lobes. Hippocampus, 9, 71–82.10.1002/(SICI)1098-1063(1999)9:1<71::AID-HIPO8>3.0.CO;2-F3.0.CO;2-F>CrossRefGoogle Scholar
Waldton, S. (1974). Clinical observations of impaired cranial nerve function in senile dementia. Acta Psychiatrica Scandinavica, 50, 539–547.CrossRefGoogle Scholar
Wenham, P.R., Price, W.H., & Blundell, G. (1991). Apolipoprotein E typing by one-stage PCR. Lancet, 337, 1158–1159.CrossRefGoogle Scholar
Youngentob, S.L., Kurtz, D.B., Leopold, D.A., Mozell, M.M., & Hornung, D.E. (1982). Olfactory sensitivity: Is there laterality? Chemical Senses, 7, 11–21.CrossRefGoogle Scholar
Yousem, D.M., Williams, S.C., Howard, R.O., Andrew, C., Simmons, A., Allin, M., Geckle, R.J., Suskind, D., Bullmore, E.T., Brammer, M.J., & Doty, R.L. (1997). Functional MR imaging during odor stimulation: Preliminary data. Radiology, 204, 833–838.CrossRefGoogle Scholar
Zald, D.H. & Pardo, J.V. (1997). Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proceedings of the National Academy of Sciences USA, 94, 4119–4124.10.1073/pnas.94.8.4119CrossRefGoogle Scholar
Zald, D.H. & Pardo, J.V. (2000). Functional neuroimaging of the olfactory system in humans. International Journal of Psychophysiology, 36, 165–181.CrossRefGoogle Scholar
Zatorre, R.J. & Jones-Gotman, M. (2000). Functional imaging of the chemical senses. In A.W. Toga & J.C. Mazziotta (Eds.), Brain mapping: The applications (pp. 403–424). San Diego, CA: Academic.Google Scholar
Zatorre, R.J., Jones-Gotman, M., Evans, A.C., & Meyer, E. (1992). Functional localization and lateralization of human olfactory cortex. Nature, 360, 339–340.CrossRefGoogle Scholar