Skip to main content
Log in

Contributions of Studies on Alcohol Use Disorders to Understanding Cerebellar Function

  • Review
  • Published:
Neuropsychology Review Aims and scope Submit manuscript

Abstract

Neuropathological, neuropsychological, and neuroimaging studies of human alcoholism provide evidence for degradation of frontal, pontine, thalamic, and cerebellar brain sites and disturbed associated functions. Current studies using neuroimaging combined with examination of executive functions, traditionally considered the sole purview of the frontal lobes, have identified a role for the cerebellum serving as a compensatory processing adjunct to enable normal performance on challenging tasks tapping executive functions. This overview proposes that disruption of an executive frontocerebellar network is a major contributor to characteristic behaviors of alcoholism that, on the one hand, enable alcohol use disorders, and on the other hand, lead to compensation for dysfunctions in alcoholism traditionally considered frontally-based.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Adams, R. D., Victor, M., & Mancall, E. L. (1959). Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. Archives of Neurology and Psychiatry, 81, 154–172.

    CAS  Google Scholar 

  • Arango, V., Underwood, M. D., & Mann, J. J. (1994). Fewer pigmented neurons in the locus coeruleus of uncomplicated alcoholics. Brain Research, 650, 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Badsberg-Jensen, G., & Pakkenberg, B. (1993). Do alcoholics drink their neurons away? Lancet, 342, 1201–1204.

    Article  Google Scholar 

  • Baker, K., Harding, A., Halliday, G., Kril, J., & Harper, C. (1999). Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neuroscience, 91, 429–438.

    Article  CAS  PubMed  Google Scholar 

  • Bartsch, A. J., Homola, G., Biller, A., Smith, S. M., Weijers, H. G., Wiesbeck, G. A., et al. (2007). Manifestations of early brain recovery associated with abstinence from alcoholism. Brain, 130, 36–47.

    Article  PubMed  Google Scholar 

  • Basser, P. J., & Pierpaoli, C. (1996). Microstructural and physiological features of tissues elucidated by quantitative diffusion tensor MRI. Journal of Magnetic Resonance. Series B, 111, 209–219.

    Article  CAS  PubMed  Google Scholar 

  • Belzunegui, T., Insausti, R., Ibanez, J., & Gonzalo, L. M. (1995). Effect of chronic alcoholism on neuronal nuclear size and neuronal population in the mammillary body and the anterior thalamic complex of man. Histology and Histopathology, 10, 633–638.

    CAS  PubMed  Google Scholar 

  • Bendszus, M., Weijers, H. G., Wiesbeck, G., Warmuth-Metz, M., Bartsch, A. J., Engels, S., et al. (2001). Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. American Journal of Neuroradiology, 22, 1926–1932.

    CAS  PubMed  Google Scholar 

  • Benegal, V., Antony, G., Venkatasubramanian, G., & Jayakumar, P. N. (2007). Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence. Addiction Biology, 12, 122–132.

    Article  PubMed  Google Scholar 

  • Biswal, B., Yetkin, F. Z., Haughton, V. M., & Hyde, J. S. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic Resonance in Medicine, 34, 537–541.

    Article  CAS  PubMed  Google Scholar 

  • Bostan AC, Strick PL (2010) Interactions between the cerebellum and basal ganglia. Neuropsychology Review, 20.

  • Cardenas, V. A., Studholme, C., Gazdzinski, S., Durazzo, T. C., & Meyerhoff, D. J. (2007). Deformation-based morphometry of brain changes in alcohol dependence and abstinence. Neuroimage, 34, 879–887.

    Article  PubMed  Google Scholar 

  • Chanraud, S., Pitel, A. L., & Sullivan, E. V. (2010a). Structural imaging of alcohol abuse. In: Shenton, M. E., & Turetsky, B. I. (Eds.). Understanding Neuropsychiatric Disorders. Cambridge University Press.

  • Chanraud, S., Pitel, A.-L., Rohlfing, T., Pfefferbaum, A., & Sullivan, E. V. (2010b). Dual tasking and working memory in alcoholism: relation to frontocerebellar circuitry. Neuropsychopharmacology, in press.

  • Chanraud, S., Martelli, C., Delain, F., Kostogianni, N., Douaud, G., Aubin, H. J., et al. (2007). Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning. Neuropsychopharmacology, 32, 429–438.

    Article  PubMed  Google Scholar 

  • Chanraud, S., Reynaud, M., Wessa, M., Penttila, J., Kostogianni, N., Cachia, A., et al. (2009). Diffusion tensor tractography in mesencephalic bundles: relation to mental flexibility in detoxified alcohol-dependent subjects. Neuropsychopharmacology, 34, 1223–1232.

    Article  PubMed  Google Scholar 

  • Courville, C. B. (1955). Effects of alcohol on the nervous system of man. Los Angeles: San Lucas Press.

    Google Scholar 

  • Cummings, J. L. (1993). Frontal-subcortical circuits and human behavior. Archives of Neurology, 50, 873–880.

    CAS  PubMed  Google Scholar 

  • De la Monte, S. M. (1988). Disproportionate atrophy of cerebral white matter in chronic alcoholics. Archives of Neurology, 45, 990–992.

    PubMed  Google Scholar 

  • De Rosa, E., Desmond, J. E., Anderson, A. K., Pfefferbaum, A., & Sullivan, E. V. (2004). The human basal forebrain integrates the old and the new. Neuron, 41, 825–837.

    Article  PubMed  Google Scholar 

  • Desmond, J. E., Gabrieli, J. D., Wagner, A. D., Ginier, B. L., & Glover, G. H. (1997). Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI. The Journal of Neuroscience, 17, 9675–9685.

    CAS  PubMed  Google Scholar 

  • Desmond, J. E., Chen, S. H., De Rosa, E., Pryor, M. R., Pfefferbaum, A., & Sullivan, E. V. (2003). Increased fronto-cerebellar activation in alcoholics during verbal working memory: an fMRI study. Neuroimage, 19, 1510–1520.

    Article  PubMed  Google Scholar 

  • Doyon, J., Gaudreau, D., Laforce, R., Jr., Castonguay, M., Bedard, P. J., Bedard, F., et al. (1997). Role of the striatum, cerebellum, and frontal lobes in the learning of a visuomotor sequence. Brain and Cognition, 34, 218–245.

    Article  CAS  PubMed  Google Scholar 

  • Durazzo, T. C., Gazdzinski, S., Banys, P., & Meyerhoff, D. J. (2004). Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study. Alcoholism, Clinical and Experimental Research, 28, 1849–1860.

    Article  CAS  PubMed  Google Scholar 

  • Durazzo, T. C., Pathak, V., Gazdzinski, S., Mon, A., & Meyerhoff, D. J. (2010). Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence. Journal of Studies on Alcohol and Drugs, 71, 278–289.

    PubMed  Google Scholar 

  • Ende, G., Welzel, H., Walter, S., Weber-Fahr, W., Diehl, A., Hermann, D., et al. (2005). Monitoring the effects of chronic alcohol consumption and abstinence on brain metabolism: a longitudinal proton magnetic resonance spectroscopy study. Biological Psychiatry, 58, 974–980.

    Article  CAS  PubMed  Google Scholar 

  • Fein, G., & Di Sclafani, V. (2004). Cerebral reserve capacity: implications for alcohol and drug abuse. Alcohol, 32, 63–67.

    Article  CAS  PubMed  Google Scholar 

  • Fein, G., Di Sclafani, V., & Finn, P. (2010). Sensation seeking in long-term abstinent alcoholics, treatment-naive active alcoholics, and nonalcoholic controls. Alcoholism, Clinical and Experimental Research, 34, 1045–1051.

    Article  PubMed  Google Scholar 

  • Fitzpatrick, L. E., Jackson, M., & Crowe, S. F. (2008). The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning. Neuroscience and Biobehavioral Reviews, 32, 466–485.

    Article  CAS  PubMed  Google Scholar 

  • Fuster, J. (1999). Synopsis of function and dysfunction of the frontal lobe. Acta Psychiatrica Scandinavica, 99, 51–57.

    Article  Google Scholar 

  • Gerig, G., Corouge, I., Vachet, C., Krishnan, K. R., & MacFall, J. R. (2005). Quantitative analysis of diffusion properties of white matter fiber tracts: a validation study. In: 13th Proceedings of the International Society for Magnetic Resonance in Medicine, p Abstract no. 1337. Miami, FL.

  • Grafman, J., Litvan, I., Massaquoi, S., Stewart, M., Sirigu, A., & Hallett, M. (1992). Cognitive planning deficit in patients with cerebellar atrophy. Neurology, 42, 1493–1496.

    CAS  PubMed  Google Scholar 

  • Guehl, D., Pessiglione, M., Francois, C., Yelnik, J., Hirsch, E. C., Feger, J., et al. (2003). Tremor-related activity of neurons in the ‘motor’ thalamus: changes in firing rate and pattern in the MPTP vervet model of parkinsonism. The European Journal of Neuroscience, 17, 2388–2400.

    Article  CAS  PubMed  Google Scholar 

  • Habas, C., Kamdar, N., Nguyen, D., Prater, K., Beckmann, C. F., Menon, V., et al. (2009). Distinct cerebellar contributions to intrinsic connectivity networks. The Journal of Neuroscience, 29, 8586–8594.

    Article  CAS  PubMed  Google Scholar 

  • Hada, M., Porjesz, B., Begleiter, H., & Polich, J. (2000). Auditory P3a assessment of male alcoholics. Biological Psychiatry, 48, 276–286.

    Article  CAS  PubMed  Google Scholar 

  • Halliday, G., Ellis, J., Heard, R., Caine, D., & Harper, C. (1993). Brainstem serotonergic neurons in chronic alcoholics with and without the memory impairment of Korsakoff’s psychosis. Journal of Neuropathology and Experimental Neurology, 52, 567–579.

    Article  CAS  PubMed  Google Scholar 

  • Harding, A., Halliday, G., Caine, D., & Kril, J. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain, 123, 141–154.

    Article  PubMed  Google Scholar 

  • Harper, C. (1998). The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? Journal Neuropathology and Experimental Neurology, 57, 101–110.

    Article  CAS  Google Scholar 

  • Harper, C. (2009). The neuropathology of alcohol-related brain damage. Alcohol and Alcoholism 44(2), 136–140.

    Article  CAS  PubMed  Google Scholar 

  • Harper, C., & Kril, J. J. (1985). Brain atrophy in chronic alcoholic patients: a quantitative pathological study. Journal of Neurology, Neurosurgery and Psychiatry, 48, 211–217.

    Article  CAS  Google Scholar 

  • Harper, C., & Kril, J. (1991). If you drink your brain will shrink: neuropathological considerations. Alcohol and Alcoholism—Supplement, 1, 375–380.

    CAS  PubMed  Google Scholar 

  • Harper, C. G., Kril, J. J., & Holloway, R. L. (1985). Brain shrinkage in chronic alcoholics: a pathological study. British Medical Journal, 290, 501–504.

    Article  CAS  PubMed  Google Scholar 

  • Harper, C. G., Kril, J. J., & Daly, J. M. (1988). Brain shrinkage in alcoholics is not caused by changes in hydration: a pathological study. Journal of Neurology, Neurosurgery and Psychiatry, 51, 124–127.

    Article  CAS  Google Scholar 

  • Harper, C., Dixon, G., Sheedy, D., & Garrick, T. (2003). Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27, 951–961.

    Article  CAS  Google Scholar 

  • Harper, C., Matsumoto, I., Pfefferbaum, A., Adalsteinsson, E., Sullivan, E. V., Lewohl, J., et al. (2005). The pathophysiology of ‘brain shrinkage’ in alcoholics structural and molecular changes and clinical implications. Alcoholism, Clinical and Experimental Research, 29, 1106–1115.

    Article  Google Scholar 

  • Hayakawa, K., & Kumagai, H. (1992). MR imaging of chronic alcoholism. Acta Radiologica, 33, 201–206.

    CAS  PubMed  Google Scholar 

  • 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, 582–587.

    CAS  PubMed  Google Scholar 

  • Hubert, V., Beaunieux, H., Chetelat, G., Platel, H., Landeau, B., Viader, F., et al. (2009). Age-related changes in the cerebral substrates of cognitive procedural learning. Human Brain Mapping, 30, 1374–1386.

    Article  PubMed  Google Scholar 

  • Jagannathan, N. R., Desai, N. G., & Raghunathan, P. (1996). Brain metabolite changes in alcoholism: an in vivo proton magnetic resonance spectroscopy (MRS) study. Magnetic Resonance Imaging, 14, 553–557.

    Article  CAS  PubMed  Google Scholar 

  • Jones, D. K. (2010). Diffusion MRI: Theory, methods, and applications (1st ed.). Oxford: Oxford University Press.

    Google Scholar 

  • Karhunen, P. J., Erkinjuntti, T., & Laippala, P. (1994). Moderate alcohol consumption and loss of cerebellar purkinje cells. British Medical Journal, 308, 1663–1667.

    CAS  PubMed  Google Scholar 

  • Kelly, R. M., & Strick, P. L. (2003a). Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. The Journal of Neuroscience, 23, 8432–8444.

    CAS  PubMed  Google Scholar 

  • Kelly, R. M., & Strick, P. L. (2003b). Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. The Journal of Neuroscience, 23, 8432–8444.

    CAS  PubMed  Google Scholar 

  • Kleinschmidt-DeMasters, B. K., Anderson, C. A., & Rubinstein, D. (1997). Asymptomatic pontine lesions found by magnetic resonance imaging: are they central pontine myelinolysis? Journal of Neurological Science, 149, 27–35.

    Article  CAS  Google Scholar 

  • Kolb, B., & Whishaw, I. Q. (1996). Fundamentals of human neuropsychology (4th ed.). New York: W. H. Freeman and Company.

    Google Scholar 

  • Krienen, F. M., & Buckner, R. L. (2009). Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cerebral Cortex, 19, 2485–2497.

    Article  PubMed  Google Scholar 

  • Kril, J. J., & Harper, C. G. (1989). Neuronal counts from four cortical regions of the alcoholic brain. Acta Neuropathol (Berl), 79, 200–204.

    Article  CAS  Google Scholar 

  • Kril, J. J., & Butterworth, R. F. (1997). Diencephalic and cerebellar pathology in alcoholic and nonalcoholic patients with end-stage liver disease. Hepatology, 26, 837–841.

    Article  CAS  PubMed  Google Scholar 

  • Le Berre, A. P., Pinon, K., Vabret, F., Pitel, A. L., Alliain, P., Eustache, F., & Beaunieux, H. (2010) Study of metamemory in patients with chronic alcoholism using a feeling-of-knowing episodic memory task. Alcoholism: Clinical & Experimental Research.

  • Le Bihan, D. (2003). Looking into the functional architecture of the brain with diffusion MRI. Nature Reviews. Neuroscience, 4, 469–480.

    Article  PubMed  CAS  Google Scholar 

  • Leggio, M. G., Chiricozzi, F. R., Clausi, S., Tedesco, A. M., & Molinari, M. (2009). The neuropsychological profile of cerebellar damage: The sequencing hypothesis. Cortex.

  • Lehericy, S., Ducros, M., Van de Moortele, P. F., Francois, C., Thivard, L., Poupon, C., et al. (2004). Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Annals of Neurology, 55, 522–529.

    Article  PubMed  Google Scholar 

  • Leiner, H. C. (2010). Solving the Mystery of the Human Cerebellum. Neuropsychology Review.

  • Lewohl, J. M., Wixey, J., Harper, C. G., & Dodd, P. R. (2005). Expression of MBP, PLP, MAG, CNP, and GFAP in the human alcoholic brain. Alcoholism, Clinical and Experimental Research, 29, 1698–1705.

    Article  CAS  PubMed  Google Scholar 

  • Lezak, M. D. (1995). Neuropsychological assessment (3rd ed.). New York: Oxford University Press.

    Google Scholar 

  • Mann, K., Agartz, I., Harper, C., Shoaf, S., Rawlings, R., Momenan, R., et al. (2001). Neuroimaging in alcoholism: ethanol and brain damage. Alcoholism: Clinical and Experimental Research (supplement), 25, 104–109S.

    Google Scholar 

  • Martin, P. R., Gibbs, S. J., Nimmerrichter, A. A., Riddle, W. R., Welch, L. W., & Willcott, M. R. (1995). Brain proton magnetic resonance spectroscopy studies in recently abstinent alcoholics. Alcoholism, Clinical and Experimental Research, 19, 1078–1082.

    Article  CAS  PubMed  Google Scholar 

  • Marvel, C. L., & Desmond, J. E. (2010). Functional topography of the cerebellum in verbal working memory. Neuropsychology Review.

  • Meyerhoff, D. J., Blumenfeld, R., Truran, D., Lindgren, J., Flenniken, D., Cardenas, V., et al. (2004). Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites. Alcoholism, Clinical and Experimental Research, 28, 650–661.

    Article  CAS  PubMed  Google Scholar 

  • Murata, T., Fujito, T., Kimura, H., Omori, M., Itoh, H., & Wada, Y. (2001). Serial MRI and (1)H-MRS of Wernicke’s encephalopathy: report of a case with remarkable cerebellar lesions on MRI. Psychiatry Research, 108, 49–55.

    Article  CAS  PubMed  Google Scholar 

  • Nixon, S. J., Tivis, R., Ceballos, N., Varner, J. L., & Rohrbaugh, J. (2002). Neurophysiological efficiency in male and female alcoholics. Progress in Neuropsychopharmacology & Biological Psychiatry, 26, 919–927.

    Article  CAS  Google Scholar 

  • Olsson, N. U., Harding, A. J., Harper, C., & Salem, N., Jr. (1996). High-performance liquid chromatography method with light-scattering detection for measurements of lipid class composition: analysis of brains from alcoholics. Journal of Chromatography. B, Biomedical Applications, 681, 213–218.

    Article  CAS  PubMed  Google Scholar 

  • Oscar-Berman, M. (2000). Neuropsychological vulnerabilities in chronic alcoholism. In A. Noronha, M. Eckardt, & K. Warren (Eds.), Review of NIAAA’s Neuroscience and Behavioral Research Portfolio, NIAAA Research Monograph No. 34 (pp. 437–472). Bethesda: National Institutes of Health.

    Google Scholar 

  • Oscar-Berman, M., & Marinkovic, K. (2007). Alcohol: effects on neurobehavioral functions and the brain. Neuropsychology Review, 17, 239–257.

    Article  PubMed  Google Scholar 

  • Oscar-Berman, M., Shagrin, B., Evert, D. L., & Epstein, C. (1997). Impairments of brain and behavior: the neurological effects of alcohol. Alcohol Health and Research World, 21, 65–75.

    CAS  PubMed  Google Scholar 

  • Parks, M. H., Dawant, B. M., Riddle, W. R., Hartmann, S. L., Dietrich, M. S., Nickel, M. K., et al. (2002). Longitudinal brain metabolic characterization of chronic alcoholics with proton magnetic resonance spectroscopy. Alcoholism, Clinical and Experimental Research, 26, 1368–1380.

    CAS  PubMed  Google Scholar 

  • Parks, M. H., Morgan, V. L., Pickens, D. R., Price, R. R., Dietrich, M. S., Nickel, M. K., et al. (2003). Brain MRI activation associated with self-paced finger-tapping in chronic alcohol dependent patients. Alcoholism, Clinical and Experimental Research, 27, 704–711.

    PubMed  Google Scholar 

  • Parks, M. H., Greenberg, D. S., Nickel, M. K., Dietrich, M. S., Rogers, B. P., & Martin, P. R. (2010). Recruitment of additional brain regions to accomplish simple motor tasks in chronic alcohol-dependent patients. Alcoholism, Clinical and Experimental Research, 34, 1098–1109.

    Article  PubMed  Google Scholar 

  • Pascual-Leone, A., Grafman, J., Clark, K., Stewart, M., Massaquoi, S., Lou, J. S., et al. (1993). Procedural learning in Parkinson’s disease and cerebellar degeneration. Annals of Neurology, 34, 594–602.

    Article  CAS  PubMed  Google Scholar 

  • Pentney, R. J. (1993). Alterations in the structure of the cerebellum after long-term ethanol consumption. In W. A. Hunt & S. J. Nixon (Eds.), Alcohol-induced brain damage: NIAAA research monograph No. 22 (pp. 249–276). Rockville: National Institute of Health.

    Google Scholar 

  • Petroff, O. A., Pleban, L. A., & Spencer, D. D. (1995). Symbiosis between in vivo and in vitro NMR spectroscopy: the creatine, N-acetylaspartate, glutamate, and GABA content of the epileptic human brain. Magnetic Resonance Imaging, 13, 1197–1211.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., & Sullivan, E. V. (2002). Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism. Neuroimage, 15, 708–718.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., & Sullivan, E. V. (2003). Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming. Magnetic Resonance in Medicine, 49, 953–961.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Lim, K. O., Zipursky, R. B., Mathalon, D. H., Rosenbloom, M. J., Lane, B., et al. (1992). Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. Alcoholism, Clinical and Experimental Research, 16, 1078–1089.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., Sullivan, E. V., Hedehus, M., Adalsteinsson, E., Lim, K. O., & Moseley, M. (2000). In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism. Alcoholism, Clinical and Experimental Research, 24, 1214–1221.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., Desmond, J. E., Galloway, C., Menon, V., Glover, G. H., & Sullivan, E. V. (2001). Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study. Neuroimage, 14, 7–20.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., Adalsteinsson, E., & Sullivan, E. V. (2003). Replicability of diffusion tensor imaging measurements of fractional anisotropy and trace in brain. Journal of Magnetic Resonance Imaging, 18, 427–433.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Adalsteinsson, E., & Sullivan, E. V. (2006). Supratentorial profile of white matter microstructural integrity in recovering alcoholic men and women. Biological Psychiatry, 59, 364–372.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Rosenbloom, M., Rohlfing, T., & Sullivan, E. V. (2009). Degradation of association and projection white matter systems in alcoholism detected with quantitative fiber tracking. Biological Psychiatry, 65, 680–690.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., Rosenbloom, M. J., Fama, R., Sassoon, S. A., & Sullivan, E. V. (2010). Transcallosal white matter degradation detected with quantitative fiber tracking in alcoholic men and women: selective relations to dissociable functions. Alcoholism, Clinical and Experimental Research, 34, 1201–1211.

    PubMed  Google Scholar 

  • Phillips, S. C., Harper, C. G., & Kril, J. (1987). A quantitative histological study of the cerebellar vermis in alcoholic patients. Brain, 110, 301–314.

    Article  PubMed  Google Scholar 

  • Pierpaoli, C., Barnett, A., Pajevic, S., Chen, R., Penix, L., Virta, A., et al. (2001). Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage, 13, 1174–1185.

    Article  CAS  PubMed  Google Scholar 

  • Rohlfing, T., Zahr, N. M., Sullivan, E. V., & Pfefferbaum, A. (2010). The SRI24 multi-channel atlas of normal adult human brain structure. Human Brain Mapping, 31, 798–819.

    Article  PubMed  Google Scholar 

  • Schmahmann, J. (1997). The cerebellum and cognition. San Diego: Academic.

    Google Scholar 

  • Schmahmann, J. (2000). The role of the cerebellum in affect and psychosis. Journal of Neurolinguistics, 13, 189–214.

    Article  Google Scholar 

  • Schmahmann, J. D. (2010). The role of the cerebellum in cognition and emotion: Personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychology Review.

  • Schmahmann, J. D., & Pandya, D. N. (1989). Anatomical investigation of projections to the basis pontis from posterior parietal association cortices in rhesus monkey. The Journal of Comparative Neurology, 289, 53–73.

    Article  CAS  PubMed  Google Scholar 

  • Schmahmann, J. D., & Pandya, D. N. (1997). The cerebrocerebellar system. In J. D. Schmahmann (Ed.), The cerebellum and cognition (pp. 31–60). San Diego: Academic.

    Google Scholar 

  • Schmahmann, J. D., & Pandya, D. N. (2008). Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems. Cortex, 44, 1037–1066.

    Article  PubMed  Google Scholar 

  • Schulte, T., Muller-Oehring, E., Rohlfing, T., Pfefferbaum, A., & Sullivan, E. V. (2010). White matter fiber degradation attenuates hemispheric asymmetry when integrating visuomotor information. Journal for Neuroscience in revision.

  • Schweinsburg, B. C., Taylor, M. J., Alhassoon, O. M., Videen, J. S., Brown, G. G., Patterson, T. L., et al. (2001). Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury. Alcoholism, Clinical and Experimental Research, 25, 924–934.

    Article  CAS  PubMed  Google Scholar 

  • Schweinsburg, B. C., Alhassoon, O. M., Taylor, M. J., Gonzalez, R., Videen, J. S., Brown, G. G., et al. (2003). Effects of alcoholism and gender on brain metabolism. The American Journal of Psychiatry, 160, 1180–1183.

    Article  PubMed  Google Scholar 

  • Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27, 2349–2356.

    Article  CAS  PubMed  Google Scholar 

  • Shear, P. K., Butters, N., Jernigan, T. L., DiTraglia, G. M., Irwin, M., Schuckit, M. A., et al. (1992). Olfactory loss in alcoholics: correlations with cortical and subcortical MRI indices. Alcohol (Fayetteville, NY), 9, 247–255.

    CAS  Google Scholar 

  • Shear, P. K., Jernigan, T. L., & Butters, N. (1994). Volumetric magnetic resonance imaging quantification of longitudinal brain changes in abstinent alcoholics. Alcoholism, Clinical and Experimental Research, 18, 172–176.

    Article  CAS  PubMed  Google Scholar 

  • Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., et al. (2006). Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage, 31, 1487–1505.

    Article  PubMed  Google Scholar 

  • Song, S. K., Sun, S. W., Ramsbottom, M. J., Chang, C., Russell, J., & Cross, A. H. (2002). Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage, 17, 1429–1436.

    Article  PubMed  Google Scholar 

  • Song, S. K., Yoshino, J., Le, T. Q., Lin, S. J., Sun, S. W., Cross, A. H., et al. (2005). Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage, 26, 132–140.

    Article  PubMed  Google Scholar 

  • Stieltjes, B., Kaufmann, W. E., van Zijl, P. C., Fredericksen, K., Pearlson, G. D., Solaiyappan, M., et al. (2001). Diffusion tensor imaging and axonal tracking in the human brainstem. Neuroimage, 14, 723–735.

    Article  CAS  PubMed  Google Scholar 

  • Stoll, A. L., Renshaw, P. F., Demicheli, E., Wurtman, R., Pillay, S. S., & Cohen, B. M. (1995). Choline ingestion increases the resonance of choline-containing compounds in human brain: an in vivo proton magnetic resonance study. Biological Psychiatry, 37, 170–174.

    Article  CAS  PubMed  Google Scholar 

  • Strick, P. L., Dum, R. P., & Fiez, J. A. (2009). Cerebellum and nonmotor function. Annual Review of Neuroscience, 32, 413–434.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V. (2000). Human brain vulnerability to alcoholism: Evidence from neuroimaging studies. In A. Noronha, M. Eckardt, & K. Warren (Eds.), Review of NIAAA’s neuroscience and behavioral research portfolio, NIAAA research monograph No. 34 (pp. 473–508). Bethesda: National Institutes of Health.

    Google Scholar 

  • Sullivan, E. V. (2003). Compromised pontocerebellar and cerebellothalamocortical systems: speculations on their contributions to cognitive and motor impairment in nonamnesic alcoholism. Alcoholism, Clinical and Experimental Research, 27, 1409–1419.

    Article  PubMed  Google Scholar 

  • Sullivan, E. V., & Pfefferbaum, A. (2001). Magnetic resonance relaxometry reveals central pontine abnormalities in clinically asymptomatic alcoholic men. Alcoholism, Clinical and Experimental Research, 25, 1206–1212.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V., & Pfefferbaum, A. (2005). Neurocircuitry in alcoholism: a substrate of disruption and repair. Psychopharmacology (Berl), 180, 583–594.

    Article  CAS  Google Scholar 

  • Sullivan, E. V., Mathalon, D. H., Lim, K. O., Marsh, L., & Pfefferbaum, A. (1998). Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism. Biological Psychiatry, 43, 118–131.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V., Rosenbloom, M. J., & Pfefferbaum, A. (2000). Pattern of motor and cognitive deficits in detoxified alcoholic men. Alcoholism, Clinical and Experimental Research, 24, 611–621.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V., Deshmukh, A., Desmond, J. E., Lim, K. O., & Pfefferbaum, A. (2000). Cerebellar volume decline in normal aging, alcoholism, and Korsakoff’s syndrome: Relation to ataxia. Neuropsychology, 14, 341–352.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V., Rosenbloom, M. J., Serventi, K. L., Deshmukh, A., & Pfefferbaum, A. (2003). Effects of alcohol dependence comorbidity and anti-psychotic medication on volumes of the thalamus and pons in schizophrenia. The American Journal of Psychiatry, 160, 1110–1116.

    Article  PubMed  Google Scholar 

  • Sullivan, E. V., Rose, J., & Pfefferbaum, A. (2006). Effect of vision, touch, and stance on cerebellar vermian-related sway and tremor: a quantitative MRI and physiological study. Cerebral Cortex, 16, 1077–1086.

    Article  PubMed  Google Scholar 

  • Sullivan, E. V., Adalsteinsson, E., & Pfefferbaum, A. (2006). Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking. Cerebral Cortex, 16, 1030–1039.

    Article  PubMed  Google Scholar 

  • Sullivan, E. V., Rohlfing, T., & Pfefferbaum, A. (2010). Pontocerebellar volume deficits and ataxia in alcoholic men and women: no evidence for “telescoping”. Psychopharmacology, 208, 279–290.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, E. V., Harris, R. A., & Pfefferbaum, A. (2010). Alcohol’s effects on brain and behavior. Alcohol Research & Health, 33, 127–143.

    Google Scholar 

  • Sun, S. W., Liang, H. F., Trinkaus, K., Cross, A. H., Armstrong, R. C., & Song, S. K. (2006). Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magnetic Resonance in Medicine, 55, 302–308.

    Article  PubMed  Google Scholar 

  • Sun, S. W., Liang, H. F., Le, T. Q., Armstrong, R. C., Cross, A. H., & Song, S. K. (2006). Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia. Neuroimage, 32, 1195–1204.

    Article  PubMed  Google Scholar 

  • Tapert, S. F., Brown, G. G., Kindermann, S. S., Cheung, E., Frank, L. R., & Brown, S. A. (2001). fMRI measurement of brain dysfunction in alcohol dependent young women. Alcoholism, Clinical and Experimental Research, 25, 236–245.

    Article  CAS  PubMed  Google Scholar 

  • Tapert, S. F., Schweinsburg, A. D., Barlett, V. C., Brown, S. A., Frank, L. R., Brown, G. G., et al. (2004). Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders. Alcoholism, Clinical and Experimental Research, 28, 1577–1586.

    Article  PubMed  Google Scholar 

  • Tedeschi, G., Bertolino, A., Righini, A., Campbell, G., Raman, R., Duyn, J. H., et al. (1995). Brain regional distribution pattern of metabolite signal intensities in young adults by proton magnetic resonance spectroscopic imaging. Neurology, 45, 1384–1391.

    CAS  PubMed  Google Scholar 

  • Urenjak, J., Williams, S. R., Gadian, D. G., & Noble, M. (1993). Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. The Journal of Neuroscience, 13, 981–989.

    CAS  PubMed  Google Scholar 

  • van der Graaf, M. (2010). In vivo magnetic resonance spectroscopy: basic methodology and clinical applications. European Biophysics Journal, 39, 527–540.

    Article  PubMed  CAS  Google Scholar 

  • Victor, M. (1987). The irrelevance of mammillary body lesions in the causation of the Korsakoff amnesic state. International Journal of Neurology, 21–22, 51–57.

    PubMed  Google Scholar 

  • Victor, M., Adam, R. D., & Mancall, E. L. (1959). A restricted form of cerebellar degeneration occurring in alcoholic patients. Archives of Neurology, 1, 577–688.

    Google Scholar 

  • Wang, G. J., Volkow, N. D., Roque, C. T., Cestaro, V. L., Hitzemann, R. J., Cantos, E. L., et al. (1993). Functional importance of ventricular enlargement and cortical atrophy in healthy subjects and alcoholics as assessed with PET, MR imaging, and neuropsychologic testing. Radiology, 186, 59–65.

    CAS  PubMed  Google Scholar 

  • Wijnia, J. W., & Goossensen, A. (2010). Cerebellar neurocognition and Korsakoff’s syndrome: an hypothesis. Medical Hypotheses, 75, 266–268.

    Article  PubMed  Google Scholar 

  • Wilson, W. (2001). The big book, Fourth Edn.

  • Witt, K., Nuhsman, A., & Deuschl, G. (2002). Dissociation of habit-learning in Parkinson’s and cerebellar disease. Journal of Cognitive Neuroscience, 14, 493–499.

    Article  CAS  PubMed  Google Scholar 

  • Xu, D., Mori, S., Solaiyappan, M., van Zijl, P. C., & Davatzikos, C. (2002). A framework for callosal fiber distribution analysis. Neuroimage, 17, 1131–1143.

    Article  PubMed  Google Scholar 

  • Yeh, P. H., Simpson, K., Durazzo, T. C., Gazdzinski, S., & Meyerhoff, D. J. (2009). Tract-Based Spatial Statistics (TBSS) of diffusion tensor imaging data in alcohol dependence: abnormalities of the motivational neurocircuitry. Psychiatry Research, 173, 22–30.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We would like to thank our colleague, Adolf Pfefferbaum, M.D. for thoughtful discussion on brain and behavioral sequelae of alcoholism and for production of the imaging figures.

Funding support

This work was funded by grants from the U.S. National Institute on Alcohol Abuse and Alcoholism (AA010723, AA017168, AA017923).

Disclosure

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Edith V. Sullivan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zahr, N.M., Pitel, AL., Chanraud, S. et al. Contributions of Studies on Alcohol Use Disorders to Understanding Cerebellar Function. Neuropsychol Rev 20, 280–289 (2010). https://doi.org/10.1007/s11065-010-9141-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11065-010-9141-y

Keywords

Navigation