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.
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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.
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.
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.
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.
Beaulieu, C. (2002). The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomedicine, 15(7–8), 435–455.
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.
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.
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.
Friston, K. J., & Frith, C. D. (1995). Schizophrenia: A disconnection syndrome? Clinical Neuroscience, 3(2), 89–97.
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.
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.
Heinrichs, R. W., & Zakzanis, K. K. (1998). Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology, 12(3), 426–445.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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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
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DOI: https://doi.org/10.1007/s11682-012-9152-9