Skip to main content

Advertisement

SpringerLink
Log in

Anterior limb of the internal capsule in schizophrenia: a diffusion tensor tractography study

  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Thalamo-cortical feedback loops play a key role in the processing and coordination of processing and integration of perceptual inputs and outputs, and disruption in this connection has long been hypothesized to contribute significantly to neuropsychological disturbances in schizophrenia. To test this hypothesis, we applied diffusion tensor tractography to 18 patients suffering schizophrenia and 20 control subjects. Fractional anisotropy (FA) was evaluated in the bilateral anterior and posterior limbs of the internal capsule, and correlated with clinical and neurocognitive measures. Patients diagnosed with schizophrenia showed significantly reduced FA bilaterally in the anterior but not the posterior limb of the internal capsule, compared with healthy control subjects. Lower FA correlated with lower scores on tests of declarative episodic memory in the patient group only. These findings suggest that disruptions, bilaterally, in thalamo-cortical connections in schizophrenia may contribute to disease-related impairment in the coordination of mnemonic processes of encoding and retrieval that are vital for efficient learning of new information.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Andreasen, N. C., O'Leary, D. S., Cizadlo, T., Arndt, S., Rezai, K., Ponto, L. L., et al. (1996). Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proceedings of the National Academy of Sciences of the United States of America, 93(18), 9985–9990.

    Article  PubMed  CAS  Google Scholar 

  • Andreasen, N. C., Paradiso, S., & O'Leary, D. S. (1998). "Cognitive dysmetria" as an integrative theory of schizophrenia: A dysfunction in cortical-subcortical-cerebellar circuitry? Schizophrenia Bulletin, 24(2), 203–218.

    Article  PubMed  CAS  Google Scholar 

  • Axer, H., & Keyserlingk, D. G. (2000). Mapping of fiber orientation in human internal capsule by means of polarized light and confocal scanning laser microscopy. Journal of Neuroscience Methods, 94(2), 165–175.

    Article  PubMed  CAS  Google Scholar 

  • Basser, P. J., Pajevic, S., Pierpaoli, C., Duda, J., & Aldroubi, A. (2000). In vivo fiber tractography using DT-MRI data. Magnetic Resonance in Medicine, 44(4), 625–632.

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu, C. (2002). The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomedicine, 15(7–8), 435–455.

    Article  PubMed  Google Scholar 

  • Brickman, A. M., Buchsbaum, M. S., Ivanov, Z., Borod, J. C., Foldi, N. S., Hahn, E., et al. (2006). Internal capsule size in good-outcome and poor-outcome schizophrenia. The Journal of Neuropsychiatry and Clinical Neurosciences, 18(3), 364–376.

    Article  PubMed  Google Scholar 

  • Buchsbaum, M. S., Schoenknecht, P., Torosjan, Y., Newmark, R., Chu, K. W., Mitelman, S., et al. (2006). Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia. Ann Gen Psychiatry, 5, 19.

    Article  PubMed  Google Scholar 

  • Byne, W., Buchsbaum, M. S., Mattiace, L. A., Hazlett, E. A., Kemether, E., Elhakem, S. L., et al. (2002). Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. The American Journal of Psychiatry, 159(1), 59–65.

    Article  PubMed  Google Scholar 

  • Friston, K. J., & Frith, C. D. (1995). Schizophrenia: A disconnection syndrome? Clinical Neuroscience, 3(2), 89–97.

    PubMed  CAS  Google Scholar 

  • Giguere, M., & Goldman-Rakic, P. S. (1988). Mediodorsal nucleus: Areal, laminar, and tangential distribution of afferents and efferents in the frontal lobe of rhesus monkeys. The Journal of Comparative Neurology, 277(2), 195–213.

    Article  PubMed  CAS  Google Scholar 

  • Hazlett, E. A., Buchsbaum, M. S., Tang, C. Y., Fleischman, M. B., Wei, T. C., Byne, W., et al. (2001). Thalamic activation during an attention-to-prepulse startle modification paradigm: A functional MRI study. Biological Psychiatry, 50(4), 281–291.

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs, R. W., & Zakzanis, K. K. (1998). Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology, 12(3), 426–445.

    Article  PubMed  CAS  Google Scholar 

  • Honey, G. D., Pomarol-Clotet, E., Corlett, P. R., Honey, R. A., McKenna, P. J., Bullmore, E. T., et al. (2005). Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function. Brain, 128(Pt 11), 2597–2611.

    Article  PubMed  Google Scholar 

  • Jeong, B., Wible, C. G., Hashimoto, R., & Kubicki, M. (2009). Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia. Human Brain Mapping, 30(12), 4138–4151.

    Article  PubMed  Google Scholar 

  • Kanaan, R. A., Shergill, S. S., Barker, G. J., Catani, M., Ng, V. W., Howard, R., et al. (2006). Tract-specific anisotropy measurements in diffusion tensor imaging. Psychiatry Research, 146(1), 73–82.

    Google Scholar 

  • Kubicki, M., Park, H., Westin, C. F., Nestor, P. G., Mulkern, R. V., Maier, S. E., et al. (2005). DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity. NeuroImage, 26(4), 1109–1118.

    Article  PubMed  CAS  Google Scholar 

  • Lang, D. J., Khorram, B., Goghari, V. M., Kopala, L. C., Vandorpe, R. A., Rui, Q., et al. (2006). Reduced anterior internal capsule and thalamic volumes in first-episode psychosis. Schizophrenia Research, 87(1–3), 89–99.

    Article  PubMed  CAS  Google Scholar 

  • Levitt, J. J., Ersner-Hershfield, H., Kubicki, M., Westin, C. F., Kikinis, R., Jolesz, F. A., McCarley, R. W., Shenton, M. E. (2004). An MR-DTI study of thalamo-cortical connections in schizophrenia. Paper presented at the Society of Biological Psychiatry Annual Meeting.

  • Liu, Y., Liang, M., Zhou, Y., He, Y., Hao, Y., Song, M., et al. (2008). Disrupted small-world networks in schizophrenia. Brain, 131(Pt 4), 945–961.

    Article  PubMed  Google Scholar 

  • Mamah, D., Conturo, T. E., Harms, M. P., Akbudak, E., Wang, L., McMichael, A. R., et al. (2010). Anterior thalamic radiation integrity in schizophrenia: a diffusion-tensor imaging study. Psychiatry Research, 183(2), 144–150.

    Article  PubMed  Google Scholar 

  • Mendrek, A., Laurens, K. R., Kiehl, K. A., Ngan, E. T., Stip, E., & Liddle, P. F. (2004). Changes in distributed neural circuitry function in patients with first-episode schizophrenia. The British Journal of Psychiatry, 185, 205–214.

    Article  PubMed  CAS  Google Scholar 

  • Mitelman, S. A., Torosjan, Y., Newmark, R. E., Schneiderman, J. S., Chu, K. W., Brickman, A. M., et al. (2007). Internal capsule, corpus callosum and long associative fibers in good and poor outcome schizophrenia: a diffusion tensor imaging survey. Schizophrenia Research, 92(1–3), 211–224.

    Article  PubMed  Google Scholar 

  • Oh, J. S., Song, I. C., Lee, J. S., Kang, H., Park, K. S., Kang, E., et al. (2007). Tractography-guided statistics (TGIS) in diffusion tensor imaging for the detection of gender difference of fiber integrity in the midsagittal and parasagittal corpora callosa. NeuroImage, 36(3), 606–616.

    Article  PubMed  Google Scholar 

  • Oh, J. S., Kubicki, M., Rosenberger, G., Bouix, S., Levitt, J. J., McCarley, R. W., et al. (2009). Thalamo-frontal white matter alterations in chronic schizophrenia: A quantitative diffusion tractography study. Human Brain Mapping, 30(11), 3812–3825.

    Article  PubMed  Google Scholar 

  • Parent, A (Ed.) (1996) (9th Edition ed.). Baltimore: Williams & Wilkins.

  • Popken, G. J., Bunney, W. E., Jr., Potkin, S. G., & Jones, E. G. (2000). Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proceedings of the National Academy of Sciences of the United States of America, 97(16), 9276–9280.

    Article  PubMed  CAS  Google Scholar 

  • Rajkowska, G., Selemon, L. D., & Goldman-Rakic, P. S. (1998). Neuronal and glial somal size in the prefrontal cortex: A postmortem morphometric study of schizophrenia and Huntington disease. Archives of General Psychiatry, 55(3), 215–224.

    Article  PubMed  CAS  Google Scholar 

  • Rosenberger, G., Kubicki, M., Nestor, P. G., Connor, E., Bushell, G. B., Markant, D., et al. (2008). Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study. Schizophrenia Research, 102(1–3), 181–188.

    Article  PubMed  Google Scholar 

  • Salat, D. H., Tuch, D. S., Hevelone, N. D., Fischl, B., Corkin, S., Rosas, H. D., et al. (2005). Age-related changes in prefrontal white matter measured by diffusion tensor imaging. Annals of the New York Academy of Sciences, 1064, 37–49.

    Article  PubMed  CAS  Google Scholar 

  • Schlosser, R., Gesierich, T., Kaufmann, B., Vucurevic, G., Hunsche, S., Gawehn, J., et al. (2003). Altered effective connectivity during working memory performance in schizophrenia: A study with fMRI and structural equation modeling. NeuroImage, 19(3), 751–763.

    Article  PubMed  Google Scholar 

  • Schneiderman, J. S., Buchsbaum, M. S., Haznedar, M. M., Hazlett, E. A., Brickman, A. M., Shihabuddin, L., et al. (2009). Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia. Neuroimage, 45(3), 662–671.

    Article  PubMed  Google Scholar 

  • Shenton, M. E., Dickey, C. C., Frumin, M., & McCarley, R. W. (2001). A review of MRI findings in schizophrenia. Schizophrenia Research, 49(1–2), 1–52.

    Article  PubMed  CAS  Google Scholar 

  • Stoll, A. L. (2001). The psychopharmacology reference card.

  • Sussmann, J. E., Lymer, G. K., McKirdy, J., Moorhead, T. W., Munoz Maniega, S., Job, D., et al. (2009). White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging. Bipolar Disorders, 11(1), 11–18.

    Article  PubMed  Google Scholar 

  • Wechsler, D. (Ed.). (1997). The WechslerMemoryScale (3 ed.).

  • Weickert, T. W., Goldberg, T. E., Gold, J. M., Bigelow, L. B., Egan, M. F., & Weinberger, D. R. (2000). Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. Archives of General Psychiatry, 57(9), 907–913.

    Article  PubMed  CAS  Google Scholar 

  • Young, K. A., Manaye, K. F., Liang, C., Hicks, P. B., & German, D. C. (2000). Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia. Biological Psychiatry, 47(11), 944–953.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, S. Y., Suzuki, M., Hagino, H., Takahashi, T., Kawasaki, Y., Nohara, S., et al. (2003). Decreased volume and increased asymmetry of the anterior limb of the internal capsule in patients with schizophrenia. Biological Psychiatry, 54(4), 427–436.

    Article  PubMed  Google Scholar 

  • Zou, L. Q., Xie, J. X., Yuan, H. S., Pei, X. L., Dong, W. T., & Liu, P. C. (2008). Diffusion tensor imaging study of the anterior limb of internal capsules in neuroleptic-naive schizophrenia. Academic Radiology, 15(3), 285–289.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Nancy Maxwell and Jennifer Goodrich for administrative support; and Georgia Bushell, B.A., Kate Smith, B.A., Jorge Alvarado, B.A., and Usman Khan, B.A. for their support as research assistants. Additionally, we gratefully acknowledge the support of the National Institute of Health (K05 MH070047 and R01 MH 50740 to MES, R01 MH 40799 to RWM and R01MH 074794, P41RR013218 and P41EB015902 to CFW, P50MH 080272 to RWM, MES), the Department of Veterans Affairs Merit Awards (MES, RWM), and the VA Schizophrenia Center Grant (RWM/MES), Neuroimage Analysis Center, NAC (NIH P41RR013218) to CFW and RK. This work is also part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant U54 EB005149 (MK, RK, MES).

Competing interest

None declared.

Author information

Authors and Affiliations

  1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Radiology, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA, 02215, USA

    Gudrun Rosenberger, Jungsu S. Oh, James J. Levitt, Martha E. Shenton & Marek Kubicki

  2. Department of General Psychiatry, Medical University Innsbruck, Innsbruck, Austria

    Gudrun Rosenberger

  3. Clinical Neuroscience Division, Laboratory of Neuroscience, Boston VA Healthcare System-Brockton Division, Department of Psychiatry, Harvard Medical School, Brockton, MA, USA

    Paul G. Nestor, James J. Levitt, Sylvain Bouix, Margaret Niznikiewicz, Robert W. McCarley, Martha E. Shenton & Marek Kubicki

  4. Department of Nuclear Medicine, Asan Medical Center, Seoul, 138-736, South Korea

    Jungsu S. Oh

  5. Laboratory of Mathematic Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Gordon Kindleman & Carl-Fredrik Westin

  6. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA, 02215, USA

    Sylvain Bouix & Jennifer Fitzsimmons

  7. Surgical Planning Laboratory, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ron Kikinis & Martha E. Shenton

Authors
  1. Gudrun Rosenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul G. Nestor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jungsu S. Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James J. Levitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gordon Kindleman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sylvain Bouix
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jennifer Fitzsimmons
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Margaret Niznikiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carl-Fredrik Westin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ron Kikinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert W. McCarley
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Martha E. Shenton
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marek Kubicki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marek Kubicki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosenberger, G., Nestor, P.G., Oh, J.S. et al. Anterior limb of the internal capsule in schizophrenia: a diffusion tensor tractography study. Brain Imaging and Behavior 6, 417–425 (2012). https://doi.org/10.1007/s11682-012-9152-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-012-9152-9

Keywords

Search

Navigation