Brain Imaging and Behavior

, Volume 8, Issue 4, pp 611–620 | Cite as

Thalamic volume deficit contributes to procedural and explicit memory impairment in HIV infection with primary alcoholism comorbidity

  • Rosemary Fama
  • Margaret J. Rosenbloom
  • Stephanie A. Sassoon
  • Torsten Rohlfing
  • Adolf Pfefferbaum
  • Edith V. Sullivan
Original Research


Component cognitive and motor processes contributing to diminished visuomotor procedural learning in HIV infection with comorbid chronic alcoholism (HIV+ALC) include problems with attention and explicit memory processes. The neural correlates associated with this constellation of cognitive and motor processes in HIV infection and alcoholism have yet to be delineated. Frontostriatal regions are affected in HIV infection, frontothalamocerebellar regions are affected in chronic alcoholism, and frontolimbic regions are likely affected in both; all three of these systems have the potential of contributing to both visuomotor procedural learning and explicit memory processes. Here, we examined the neural correlates of implicit memory, explicit memory, attention, and motor tests in 26 HIV+ALC (5 with comorbidity for nonalcohol drug abuse/dependence) and 19 age-range matched healthy control men. Parcellated brain volumes, including cortical, subcortical, and allocortical regions, as well as cortical sulci and ventricles, were derived using the SRI24 brain atlas. Results indicated that smaller thalamic volumes were associated with poorer performance on tests of explicit (immediate and delayed) and implicit (visuomotor procedural) memory in HIV+ALC. By contrast, smaller hippocampal volumes were associated with lower scores on explicit, but not implicit memory. Multiple regression analyses revealed that volumes of both the thalamus and the hippocampus were each unique independent predictors of explicit memory scores. This study provides evidence of a dissociation between implicit and explicit memory tasks in HIV+ALC, with selective relationships observed between hippocampal volume and explicit but not implicit memory, and highlights the relevance of the thalamus to mnemonic processes.


Visuomotor procedural learning Implicit memory Explicit memory Thalamus Hippocampus HIV infection-alcoholism comorbidity 



This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism AA017347, AA005965, AA010723, and AA017168.


  1. Aggleton, J. P., & Saunders, R. C. (1997). The relationships between temporal lobe and diencephalic structures implicated in anterograde amnesia. Memory, 5(1–2), 49–71.PubMedCrossRefGoogle Scholar
  2. Aggleton, J. P., O’Mara, S. M., Vann, S. D., Wright, N. F., Tsanov, M., & Erichsen, J. T. (2010). Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. European Journal of Neuroscience, 31(12), 2292–2307.PubMedCentralPubMedCrossRefGoogle Scholar
  3. Alexander, G., DeLong, M., & Strick, P. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357–381.PubMedCrossRefGoogle Scholar
  4. Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the beck depression inventory-II. San Antonio: Psychological Corporation.Google Scholar
  5. Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society, Series B, 57(1), 289–300.Google Scholar
  6. Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N., & Golani, I. (2001). Controlling the false discovery rate in behavior genetics research. Behavioural Brain Research, 125(1–2), 279–284.PubMedCrossRefGoogle Scholar
  7. Bondi, M. W., & Kaszniak, A. W. (1991). Implicit and explicit memory in Alzheimer’s disease and Parkinson’s disease. Journal of Clinical and Experimental Neuropsychology, 13, 339–358.PubMedCrossRefGoogle Scholar
  8. 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. Journal of Neuroscience, 15(1 Part 1), 12–29.PubMedGoogle Scholar
  9. Buxton, C. E., & Grant, D. A. (1939). Retroaction and gains in motor learning: II. Sex differences, and a further analysis of gains. Journal of Experimental Psychology, 25(2), 198–208.CrossRefGoogle Scholar
  10. Bylsma, F. W., Rebok, G. W., & Brandt, J. (1991). Long-term retention of implicit learning in Huntington’s disease. Neuropsychologia, 29, 1213–1221.PubMedCrossRefGoogle Scholar
  11. Carlesimo, G., & Oscar-Berman, M. (1992). Memory deficits in Alzheimer patients: a comprehensive review. Neuropsychology Review, 3, 119–169.PubMedCrossRefGoogle Scholar
  12. Carlesimo, G. A., Lombardi, M. G., & Caltagirone, C. (2011). Vascular thalamic amnesia: a reappraisal. Neuropsychologia, 49(5), 777–789.PubMedCrossRefGoogle Scholar
  13. Castelo, J. M., Sherman, S. J., Courtney, M. G., Melrose, R. J., & Stern, C. E. (2006). Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology, 66(11), 1688–1695.PubMedCrossRefGoogle Scholar
  14. Chang, L., Speck, O., Miller, E. N., Braun, J., Jovicich, J., Koch, C., Itti, L., & Ernst, T. (2001). Neural correlates of attention and working memory deficits in HIV patients. Neurology, 57(6), 1001–1007.PubMedCrossRefGoogle Scholar
  15. Clifford, D. B., & Ances, B. M. (2013). HIV-associated neurocognitive disorder. Lancet Infectious Diseases, 13, 976–986.CrossRefGoogle Scholar
  16. Cohen, N. J. (1984). Preserved learning capacity in amnesia: Evidence for multiple memory systems. In L. R. Squire & N. Butters (Eds.), Neuropsychology of memory. New York: Guilford Press.Google Scholar
  17. Corkin, S. (1968). Acquisition of motor skills after bilateral medial temporal lobe excision. Neuropsychologia, 6, 255–256.CrossRefGoogle Scholar
  18. Crosson, B. (1992). Subcortical functions in language and memory. New York: The Guilford Press.Google Scholar
  19. Doyon, J., Penhune, V., & Ungerleider, L. G. (2003). Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252–262.PubMedCrossRefGoogle Scholar
  20. Exner, C., Weniger, G., & Irle, E. (2001). Implicit and explicit memory after focal thalamic lesions. Neurology, 57, 2054–2063.PubMedCrossRefGoogle Scholar
  21. Fama, R., Pfefferbaum, A., & Sullivan, E. V. (2006). Visuoperceptual priming in alcoholic Korsakoff syndrome. Alcoholism, Clinical and Experimental Research, 30, 680–687.PubMedCrossRefGoogle Scholar
  22. Fama, R., Rosenbloom, M. J., Sassoon, S. A., Pfefferbaum, A., & Sullivan, E. V. (2012). Differential effect of alcoholism and HIV infection on visuomotor procedural learning and retention. Alcoholism, Clinical and Experimental Research, 36(10), 1738–1747.PubMedCentralPubMedCrossRefGoogle Scholar
  23. First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1998). Structured clinical interview for DSM-IV axis I disorders (SCID) version 2.0. New York: Biometrics Research Department, New York State Psychiatric Institute.Google Scholar
  24. Fregly, A. R., Graybiel, A., & Smith, M. S. (1972). Walk on floor eyes closed (WOFEC): a new addition to an ataxia test battery. Aerospace Medicine, 43(4), 395–399.PubMedGoogle Scholar
  25. Gonzalez, R., Jacobus, J., Amatya, A. K., Quartana, P. J., Vassileva, J., & Martin, E. M. (2008). Deficits in complex motor functions, despite no evidence of procedural learning deficits, among HIV+individuals with history of substance dependence. Neuropsychology, 22(6), 776–786.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Harding, A., Halliday, G., Caine, D., & Kril, J. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain, 123(Pt 1), 141–154.PubMedCrossRefGoogle Scholar
  27. Harper, C. G., & Kril, J. J. (1993). Neuropathological changes in alcoholics. In W. A. Hunt & S. J. Nixon (Eds.), Alcohol induced brain damage: NIAAA research monograph no. 22 (pp. 39–69). Rockville, MD: National Institute of Health.Google Scholar
  28. Heaton, R., Franklin, D., Ellis, R., McCutchan, J., Letendre, S., LeBlanc, S., Corkran, S., Duarte, N., Clifford, D., Woods, S., Collier, A., Marra, C., Morgello, C., Mindt, M., Taylor, M., Marcotte, T., Atkinson, J. H., Wolfson, T., Gelman, B., McArthur, J., Simpson, D., Abramson, I., Gamst, A., Fennema-Notestine, C., Jernigan, T., Wong, J., & Grant, I. (2011). HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. Journal of Neurovirology, 17, 3–16.PubMedCentralPubMedCrossRefGoogle Scholar
  29. Heindel, W. C., Butters, M., & Salmon, D. P. (1988). Impaired learning of a motor skill in patients with Huntington’s disease. Behavioral Neuroscience, 102(1), 141–147.PubMedCrossRefGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. Karnofsky, D. A. (1949). The clinical evaluation of chemotherapeutic agents in cancer. In C. M. MacLeod (Ed.), Evaluation of chemotherapeutic agents (pp. 191–205). New York: Columbia University Press.Google Scholar
  32. Kim, E., Ku, J., Jung, Y.-C., Lee, H., Kim, S. I., Kim, J.-J., Namkoong, K., & Song, D.-H. (2010). Restoration of mammilothalamic functional connectivity through thiamine replacement therapy in Wernicke’s encephalopathy. Neuroscience Letters, 479, 257–261.PubMedCrossRefGoogle Scholar
  33. Maki, P. M., & Martin-Thormeyer, E. (2009). HIV, cognition and women. Neuropsychology Review, 19, 204–214.PubMedCentralPubMedCrossRefGoogle Scholar
  34. Maki, P. M., Cohen, M. H., Weber, K., Little, D. M., Fornelli, D., Rubin, L. H., Perschler, P., Gould, F., & Martin, E. (2009). Impairments in memory and hippocampal function in HIV-positive vs. HIV-negative women: a preliminary study. Neurology, 72(19), 1661–1668.PubMedCentralPubMedCrossRefGoogle Scholar
  35. Metzger, C. D., van der Werf, Y. D., & Walter, M. (2013). Functional mapping of thalamic nuclei and their integration into cortico-striatal-thalamo-cortical loops via ultra-high resolution imaging-from animal anatomy to in vivo imaging in humans. Frontiers in Neuroscience, 7, 24.PubMedCentralPubMedCrossRefGoogle Scholar
  36. Nelson, H. E. (1982). The national adult reading test (NART). Windsor: Nelson Publishing Company.Google Scholar
  37. Pfefferbaum, A., Rosenbloom, M. J., Sassoon, S. A., Kemper, C. A., Deresinski, S., Rohlfing, T., & Sullivan, E. V. (2012). Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age. Biological Psychiatry, 72(5), 361–370.PubMedCentralPubMedCrossRefGoogle Scholar
  38. Reber, P. (2013). The neural basis of implicit learning and memory: a review of neuropsychological and neuroimaging research. Neuropsychologia, 51, 2026–2042.PubMedCrossRefGoogle Scholar
  39. 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(5), 798–819.PubMedCentralPubMedCrossRefGoogle Scholar
  40. Rothlind, J. C., Greenfield, T. M., Bruce, A. V., Meyerhoff, D. J., Flenniken, D. L., Lindgren, J. A., & Weiner, M. W. (2005). Heavy alcohol consumption in individuals with HIV infection: effects on neuropsychological performance. Journal of the International Neuropsychological Society, 11(1), 70–83.PubMedCentralPubMedCrossRefGoogle Scholar
  41. Sassoon, S. A., Rosenbloom, M. J., Fama, R., Sullivan, E. V., & Pfefferbaum, A. (2012). Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity. Psychiatry Research, 199(2), 102–110.PubMedCentralPubMedCrossRefGoogle Scholar
  42. Serra, L., Cercignani, M., Carlesimo, G. A., Fadda, L., Tini, N., Giulietti, G., Caltagirone, C., & Bozzali, M. (2013). Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct. PLoS One, 8(6), e64578.PubMedCentralPubMedCrossRefGoogle Scholar
  43. Skinner, H. A. (1982). Development and validation of a lifetime alcohol consumption assessment procedure. Toronto: Addiction Research Foundation.Google Scholar
  44. Skinner, H. A., & Sheu, W. J. (1982). Reliability of alcohol use indices: the lifetime drinking history and the MAST. Journal of Studies on Alcohol, 43, 1157–1170.PubMedGoogle Scholar
  45. Smith, A. (1973). The symbol digit modalities test manual. Los Angeles: Western Psychological Services.Google Scholar
  46. Squire, L. R. (1982). Comparisons between forms of amnesia: some deficits are unique to Korsakoff’s syndrome. Journal of Experimental Psychology: Learning, Memory, and Cognition, 8, 560–571.PubMedGoogle Scholar
  47. Stein, T., Moritz, C., Quigley, M., Cordes, D., Haughton, V., & Meyerand, E. (2000). Functional connectivity in the thalamus and hippocampus studied with functional MR imaging. AJNR. American Journal of Neuroradiology, 21(8), 1397–1401.PubMedGoogle Scholar
  48. Sturm, W., & Willmes, K. (2001). On the functional neuroanatomy of intrinsic and phasic alertness. NeuroImage, 14(1 Pt 2), S76–S84.PubMedCrossRefGoogle Scholar
  49. 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(9), 1409–1419.PubMedCrossRefGoogle Scholar
  50. Sullivan, E. V., Pfefferbaum, A., Rohlfing, T., Baker, F. C., Padilla, M. L., & Colrain, I. M. (2011). Developmental change in regional brain structure over 7 months in early adolescence: comparison of approaches for longitudinal atlas-based parcellation. NeuroImage, 57, 214–224.PubMedCentralPubMedCrossRefGoogle Scholar
  51. Thomson, A. D., Marshall, E. J., & Guerrini, I. (2010). Biomarkers for detecting thiamine deficiency–improving confidence and taking a comprehensive history are also important. Alcohol and Alcoholism, 45(2), 213.PubMedCrossRefGoogle Scholar
  52. Van der Werf, Y. D., Witter, M. P., Uylings, H. B., & Jolles, J. (2000). Neuropsychology of infarctions in the thalamus: a review. Neuropsychologia, 38(5), 613–627.PubMedCrossRefGoogle Scholar
  53. Victor, M., Adams, R. D., & Collins, G. H. (1989). The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition (2nd ed.). Philadelphia: Davis.Google Scholar
  54. Wechsler, D. (1987). Wechsler memory scale–revised. San Antonio: The Psychological Corporation.Google Scholar
  55. Woods, S., Moore, D., Weber, E., & Grant, I. (2009). Cognitive neuropsychology of HIV associated neurocognitive disorders. Neuropsychology Review, 19(2), 152–168.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rosemary Fama
    • 1
    • 2
  • Margaret J. Rosenbloom
    • 1
    • 2
  • Stephanie A. Sassoon
    • 2
  • Torsten Rohlfing
    • 2
  • Adolf Pfefferbaum
    • 1
    • 2
  • Edith V. Sullivan
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesStanford University School of Medicine (MC5723)StanfordUSA
  2. 2.Neuroscience ProgramSRI InternationalMenlo ParkUSA

Personalised recommendations