Brain Imaging and Behavior

, Volume 10, Issue 4, pp 1054–1067 | Cite as

Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD)

  • Nikolaos MakrisEmail author
  • Yogesh Rathi
  • Palig Mouradian
  • Giorgio Bonmassar
  • George Papadimitriou
  • Wingkwai I. Ing
  • Edward H. Yeterian
  • Marek Kubicki
  • Emad N. Eskandar
  • Lawrence L. Wald
  • Qiuyun Fan
  • Aapo Nummenmaa
  • Alik S. Widge
  • Darin D. Dougherty
Original Research


Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.


Diffusion tensor imaging Diffusion tractography Connectome Obsessive-compulsive disorder (OCD) Deep brain stimulation (DBS) Tractography-guided DBS 



The authors would also like to acknowledge Dr. Jonathan Polimeni and Dr. Emad Ahmadi for assisting with acquisition of postmortem material MRI data.

Compliance with ethical standards


This study was supported, in part, by grants from: NIH, NIBIB R21EB016449 (NM and GB); from NIH, 5 UO1 MH 093765-05 (LW, QF and AN); from NIMH, RO1MH097979 (YR); from NIMH, R01 MH102377 (MK and NM); from Colby College Research Fund 01 2836 (EY); from Medtronic, Cyberonics, Roche and Eli Lilly and Company (DD).

Conflicts of interest

Nikolaos Makris, Yogesh Rathi, Palig Mouradian, Giorgio Bonmassar, George Papadimitriou, Wingkwai I. Ing, Edward H. Yeterian, Marek Kubicki, Lawrence Wald, Qiuyun Fan, Aapo Nummenmaa declare that they have no conflict of interest. Darin D. Dougherty has receivedspeaker honoraria from Insys and Johnson & Johnson, and has received research grants from Medtronic, Cyberonics, Roche and Eli Lilly. Alik S. Widge, Darin Dougherty and Emad N. Eskandar are named inventors on patents related to improved targeting and delivery of deep brain stimulation.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients included in the study.


  1. Ahmari, S. E., Spellman, T., Douglass, N. L., Kheirbek, M. A., Simpson, H. B., Deisseroth, K., et al. (2013). Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science, 340(6137), 1234–1239. doi: 10.1126/science.1234733.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Andrew, J., & Watkins, S. (1969). A stereotaxic atlas of the human thalamus and adjacent structures; a variability study. Baltimore: Williams & Wilkins.Google Scholar
  3. Anticevic, A., Hu, S., Zhang, S., Savic, A., Billingslea, E., Wasylink, S., et al. (2014). Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biological Psychiatry, 75(8), 595–605. doi: 10.1016/j.biopsych.2013.10.021.CrossRefPubMedGoogle Scholar
  4. Arikuni, T., Sakai, M., & Kubota, K. (1983). Columnar aggregation of prefrontal and anterior cingulate cortical cells projecting to the thalamic mediodorsal nucleus in the monkey. Journal of Comparative Neurology, 220(1), 116–125. doi: 10.1002/cne.902200111.CrossRefPubMedGoogle Scholar
  5. Ayuso-Mateos, J. (2002). Global burden of obsessive compulsive disorders in the year 2000. Geneva: World Health Organization.Google Scholar
  6. Barbas, H., Henion, T. H., & Dermon, C. R. (1991). Diverse thalamic projections to the prefrontal cortex in the rhesus monkey. Journal of Comparative Neurology, 313(1), 65–94. doi: 10.1002/cne.903130106.CrossRefPubMedGoogle Scholar
  7. Basser, P. J. (2004). Scaling laws for myelinated axons derived from an electrotonic core-conductor model. Journal of Integrative Neuroscience, 3(2), 227–244.CrossRefPubMedGoogle Scholar
  8. Baumgartner, C., Pasternak, O., Bouix, S., Westin, C. F., Rathi, Y. (2012). Filtered multi-tensor tractography using free water estimation. Paper presented at the ISMRM, Melbourne, Australia.Google Scholar
  9. Behrens, T. E., Berg, H. J., Jbabdi, S., Rushworth, M. F., & Woolrich, M. W. (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage, 34(1), 144–155, doi: 10.1016/j.neuroimage.2006.09.018.
  10. Bonmassar, G., & Makris, N. (2015). Connectome Pathways in Parkinson’s Disease Patients with Deep Brain Stimulators. Paper presented at the Cogn Int Conf Adv Cogn Technol Appl, Nice, France.Google Scholar
  11. Bos, J., & Benevento, L. A. (1975). Projections of the medial pulvinar to orbital cortex and frontal eye fields in the rhesus monkey (Macaca mulatta). Experimental Neurology, 49(2), 487–496.CrossRefPubMedGoogle Scholar
  12. Burguiere, E., Monteiro, P., Feng, G., & Graybiel, A. M. (2013). Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science, 340(6137), 1243–1246. doi: 10.1126/science.1232380.CrossRefPubMedGoogle Scholar
  13. Cavada, C., Company, T., Tejedor, J., Cruz-Rizzolo, R. J., & Reinoso-Suarez, F. (2000). The anatomical connections of the macaque monkey orbitofrontal cortex. A review. Cerebral Cortex, 10(3), 220–242.CrossRefPubMedGoogle Scholar
  14. Chaturvedi, A., Lujan, J. L., & McIntyre, C. C. (2013). Artificial neural network based characterization of the volume of tissue activated during deep brain stimulation. Journal of Neural Engineering, 10(5), 056023, doi: 10.1088/1741-2560/10/5/056023.
  15. Cuthbert, B. N., & Insel, T. R. (2010). Toward new approaches to psychotic disorders: the NIMH research domain criteria project. Schizophrenia Bulletin, 36(6), 1061–1062. doi: 10.1093/schbul/sbq108.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Medicine, 11, 126. doi: 10.1186/1741-7015-11-126.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. NeuroImage, 9(2), 179–194. doi: 10.1006/nimg.1998.0395.CrossRefPubMedGoogle Scholar
  18. Desikan, R. S., Segonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., et al. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980. doi: 10.1016/j.neuroimage.2006.01.021.CrossRefPubMedGoogle Scholar
  19. Dougherty, D. D., Rauch, S. L., Greenberg, B. D. (2010). Pathophysiology of obsessive-compulsive disorders. In D. J. Stein, E. Hollander, R. B. O. (Eds.), Textbook of Anxiety Disorders (2nd ed.). Washington, D.C.: APPI; Edinburgh : Compass Academic [distributor].Google Scholar
  20. Erickson, S. L., & Lewis, D. A. (2004). Cortical connections of the lateral mediodorsal thalamus in cynomolgus monkeys. Journal of Comparative Neurology, 473(1), 107–127. doi: 10.1002/cne.20084.CrossRefPubMedGoogle Scholar
  21. Evans, A. C., Collins, D. L., Mills, S. R., Brown, E. D., Kelly, R. L., Peters, T. M. (1993). 3D statistical neuroanatomical model from 305 MRI volumes. Paper presented at the Nuclear Science Symposium and Medical Imaging Conference.Google Scholar
  22. Fineberg, N. A., Potenza, M. N., Chamberlain, S. R., Berlin, H. A., Menzies, L., Bechara, A., et al. (2010). Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology, 35(3), 591–604. doi: 10.1038/npp.2009.185.CrossRefPubMedGoogle Scholar
  23. Fischl, B., & Dale, A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences of the United States of America, 97(20), 11050–11055. doi: 10.1073/pnas.200033797.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: inflation, flattening, and a surface-based coordinate system. NeuroImage, 9(2), 195–207. doi: 10.1006/nimg.1998.0396.CrossRefPubMedGoogle Scholar
  25. Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., et al. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355.CrossRefPubMedGoogle Scholar
  26. Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D. H., et al. (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14(1), 11–22.CrossRefPubMedGoogle Scholar
  27. Galaburda, A. M., Corsiglia, J., Rosen, G. D., & Sherman, G. F. (1987). Planum temporale asymmetry, reappraisal since Geschwind and Levitsky. Neuropsychologia, 25(6), 853–868.CrossRefGoogle Scholar
  28. 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. Journal of Comparative Neurology, 277(2), 195–213. doi: 10.1002/cne.902770204.CrossRefPubMedGoogle Scholar
  29. Goldman-Rakic, P. S., & Porrino, L. J. (1985). The primate mediodorsal (MD) nucleus and its projection to the frontal lobe. Journal of Comparative Neurology, 242(4), 535–560. doi: 10.1002/cne.902420406.CrossRefPubMedGoogle Scholar
  30. Graybiel, A. M., & Rauch, S. L. (2000). Toward a neurobiology of obsessive-compulsive disorder. Neuron, 28(2), 343–347.CrossRefPubMedGoogle Scholar
  31. Greenberg, B. D., Gabriels, L. A., Malone, D. A., Jr., Rezai, A. R., Friehs, G. M., Okun, M. S., et al. (2010a). Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Molecular Psychiatry, 15(1), 64–79. doi: 10.1038/mp.2008.55.CrossRefPubMedGoogle Scholar
  32. Greenberg, B. D., Rauch, S. L., & Haber, S. N. (2010b). Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. Neuropsychopharmacology, 35(1), 317–336. doi: 10.1038/npp.2009.128.CrossRefPubMedGoogle Scholar
  33. Greist, J. H., Jefferson, J. W., Kobak, K. A., Katzelnick, D. J., & Serlin, R. C. (1995). Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Archives of General Psychiatry, 52(1), 53–60.CrossRefPubMedGoogle Scholar
  34. Hsu, D. T., & Price, J. L. (2007). Midline and intralaminar thalamic connections with the orbital and medial prefrontal networks in macaque monkeys. Journal of Comparative Neurology, 504(2), 89–111. doi: 10.1002/cne.21440.CrossRefPubMedGoogle Scholar
  35. Jakab, A., Blanc, R., & Berenyi, E. L. (2012). Mapping changes of in vivo connectivity patterns in the human mediodorsal thalamus: correlations with higher cognitive and executive functions. Brain Imaging and Behavior, 6(3), 472–483. doi: 10.1007/s11682-012-9172-5.CrossRefPubMedGoogle Scholar
  36. Jang, S. H., & Yeo, S. S. (2014). Thalamocortical connections between the mediodorsal nucleus of the thalamus and prefrontal cortex in the human brain: a diffusion tensor tractographic study. Yonsei Medical Journal, 55(3), 709–714. doi: 10.3349/ymj.2014.55.3.709.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Jbabdi, S., Lehman, J. F., Haber, S. N., & Behrens, T. E. (2013). Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography. Journal of Neuroscience, 33(7), 3190–3201. doi: 10.1523/JNEUROSCI.2457-12.2013.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Kievit, J., & Kuypers, H. G. (1977). Organization of the thalamo-cortical connexions to the frontal lobe in the rhesus monkey. Experimental Brain Research, 29(3–4), 299–322.PubMedGoogle Scholar
  39. Klein, J. C., Rushworth, M. F., Behrens, T. E., Mackay, C. E., de Crespigny, A. J., D’Arceuil, H., et al. (2010). Topography of connections between human prefrontal cortex and mediodorsal thalamus studied with diffusion tractography. NeuroImage, 51(2), 555–564. doi: 10.1016/j.neuroimage.2010.02.062.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Koran, L. M., Hanna, G. L., Hollander, E., Nestadt, G., Simpson, H. B., & American Psychiatric, A. (2007). Practice guideline for the treatment of patients with obsessive-compulsive disorder. The American Journal of Psychiatry, 164(7 Suppl), 5–53.PubMedGoogle Scholar
  41. Laidlaw, T. M., Falloon, I. R., Barnfather, D., & Coverdale, J. H. (1999). The stress of caring for people with obsessive compulsive disorders. Community Mental Health Journal, 35(5), 443–450.CrossRefPubMedGoogle Scholar
  42. Lehman, J. F., Greenberg, B. D., McIntyre, C. C., Rasmussen, S. A., & Haber, S. N. (2011). Rules ventral prefrontal cortical axons use to reach their targets: implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness. Journal of Neuroscience, 31(28), 10392–10402. doi: 10.1523/JNEUROSCI.0595-11.2011.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Makris, N., Meyer, J. W., Bates, J. F., Yeterian, E. H., Kennedy, D. N., & Caviness, V. S. (1999). MRI-Based topographic parcellation of human cerebral white matter and nuclei II. Rationale and applications with systematics of cerebral connectivity. NeuroImage, 9(1), 18–45. doi: 10.1006/nimg.1998.0384.CrossRefPubMedGoogle Scholar
  44. Makris, N., Preti, M. G., Asami, T., Pelavin, P., Campbell, B., Papadimitriou, G. M., et al. (2013a). Human middle longitudinal fascicle: variations in patterns of anatomical connections. Brain Structure and Function, 218(4), 951–968. doi: 10.1007/s00429-012-0441-2.CrossRefPubMedGoogle Scholar
  45. Makris, N., Preti, M. G., Wassermann, D., Rathi, Y., Papadimitriou, G. M., Yergatian, C., et al. (2013b). Human middle longitudinal fascicle: segregation and behavioral-clinical implications of two distinct fiber connections linking temporal pole and superior temporal gyrus with the angular gyrus or superior parietal lobule using multi-tensor tractography. Brain Imaging and Behavior, 7(3), 335–352. doi: 10.1007/s11682-013-9235-2.CrossRefPubMedGoogle Scholar
  46. Malcolm, J. G., Shenton, M. E., & Rathi, Y. (2010). Filtered multitensor tractography. IEEE Transactions on Medical Imaging, 29(9), 1664–1675. doi: 10.1109/TMI.2010.2048121.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mancebo, M. C., Greenberg, B., Grant, J. E., Pinto, A., Eisen, J. L., Dyck, I., et al. (2008). Correlates of occupational disability in a clinical sample of obsessive-compulsive disorder. Comprehensive Psychiatry, 49(1), 43–50. doi: 10.1016/j.comppsych.2007.05.016.CrossRefPubMedGoogle Scholar
  48. McFarland, N. R., & Haber, S. N. (2002). Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical areas. Journal of Neuroscience, 22(18), 8117–8132.PubMedGoogle Scholar
  49. Mega, M. S., Cummings, J. L., Salloway, S., Malloy, P. (2005). The limbic system. In The neuropsychiatry of limbic and subcortical disorders (pp. 3–18): American Psychiatric Press, Inc.Google Scholar
  50. Milad, M. R., & Rauch, S. L. (2012). Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends in Cognitive Sciences, 16(1), 43–51. doi: 10.1016/j.tics.2011.11.003.CrossRefPubMedGoogle Scholar
  51. Morecraft, R. J., Geula, C., & Mesulam, M. M. (1992). Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey. Journal of Comparative Neurology, 323(3), 341–358. doi: 10.1002/cne.903230304.CrossRefPubMedGoogle Scholar
  52. Pallanti, S., Hollander, E., Bienstock, C., Koran, L., Leckman, J., Marazziti, D., et al. (2002). Treatment non-response in OCD: methodological issues and operational definitions. International Journal of Neuropsychopharmacology, 5(2), 181–191. doi: 10.1017/S1461145702002900.CrossRefPubMedGoogle Scholar
  53. Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014). Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nature Reviews Neuroscience, 15(6), 410–424. doi: 10.1038/nrn3746.CrossRefPubMedGoogle Scholar
  54. Pittenger, C., & Bloch, M. H. (2014). Pharmacological treatment of obsessive-compulsive disorder. The Psychiatric Clinics of North America, 37(3), 375–391. doi: 10.1016/j.psc.2014.05.006.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Posner, J., Marsh, R., Maia, T. V., Peterson, B. S., Gruber, A., & Simpson, H. B. (2014). Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder. Human Brain Mapping, 35(6), 2852–2860. doi: 10.1002/hbm.22371.CrossRefPubMedGoogle Scholar
  56. Rathi, Y., Gagoski, B., Setsompop, K., Michailovich, O., Grant, P. E., & Westin, C. F. (2013). Diffusion propagator estimation from sparse measurements in a tractography framework. Med Image Comput Comput Assist Interv, 16(Pt 3), 510–517.Google Scholar
  57. Rathi, Y., Malcolm, J. G., Bouix, S., Westin, C. F., & Shenton, M. (2010). False positive detection using filtered tractography. Paper presented at the International Society For Magnetic Resonance in Medicine Scientific Meeting (ISMRM), Stockholm.Google Scholar
  58. Ray, J. P., & Price, J. L. (1993). The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys. Journal of Comparative Neurology, 337(1), 1–31. doi: 10.1002/cne.903370102.CrossRefPubMedGoogle Scholar
  59. Romanski, L. M., Giguere, M., Bates, J. F., & Goldman-Rakic, P. S. (1997). Topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus monkey. Journal of Comparative Neurology, 379(3), 313–332.CrossRefPubMedGoogle Scholar
  60. Russchen, F. T., Amaral, D. G., & Price, J. L. (1987). The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis. Journal of Comparative Neurology, 256(2), 175–210. doi: 10.1002/cne.902560202.CrossRefPubMedGoogle Scholar
  61. Setsompop, K., Kimmlingen, R., Eberlein, E., Witzel, T., Cohen-Adad, J., McNab, J. A., et al. (2013). Pushing the limits of in vivo diffusion MRI for the human connectome project. NeuroImage, 80, 220–233. doi: 10.1016/j.neuroimage.2013.05.078.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Siwek, D. F., & Pandya, D. N. (1991). Prefrontal projections to the mediodorsal nucleus of the thalamus in the rhesus monkey. Journal of Comparative Neurology, 312(4), 509–524. doi: 10.1002/cne.903120403.CrossRefPubMedGoogle Scholar
  63. 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(3), 1429–1436.CrossRefPubMedGoogle Scholar
  64. Song, S. K., Sun, S. W., Ju, W. K., Lin, S. J., Cross, A. H., & Neufeld, A. H. (2003). Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. NeuroImage, 20(3), 1714–1722.CrossRefPubMedGoogle Scholar
  65. Talairach, J., David, M., Tournoux, P., Corredor, H., & Kvasina, T. (1957). Atlas d’anatomie stéréotaxique des noyaux gris centraux. Paris: Masson.Google Scholar
  66. Tobias, T. J. (1975). Afferents to prefrontal cortex from the thalamic mediodorsal nucleus in the rhesus monkey. Brain Research, 83(2), 191–212.CrossRefPubMedGoogle Scholar
  67. Trojanowski, J. Q., & Jacobson, S. (1976). Areal and laminar distribution of some pulvinar cortical efferents in rhesus monkey. Journal of Comparative Neurology, 169(3), 371–392. doi: 10.1002/cne.901690307.CrossRefPubMedGoogle Scholar
  68. Wassermann, D., Makris, N., Rathi, Y., Shenton, M., Kikinis, R., Kubicki, M., et al. (2013). On describing human white matter anatomy: the white matter query language. Med Image Comput Comput Assist Interv, 16(Pt 1), 647–654.PubMedPubMedCentralGoogle Scholar
  69. Xiao, D., & Barbas, H. (2002). Pathways for emotions and memory. II. Afferent input to the anterior thalamic nuclei from prefrontal, temporal, hypotha- lamic areas and the basal ganglia in the rhesus monkey. Thalamus Related Systems, 2(1), 33–48.Google Scholar
  70. Xiao, D., Zikopoulos, B., & Barbas, H. (2009). Laminar and modular organization of prefrontal projections to multiple thalamic nuclei. Neuroscience, 161(4), 1067–1081. doi: 10.1016/j.neuroscience.2009.04.034.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Yang, J. C., Ginat, D. T., Dougherty, D. D., Makris, N., & Eskandar, E. N. (2014). Lesion analysis for cingulotomy and limbic leucotomy: comparison and correlation with clinical outcomes. Journal of Neurosurgery, 120(1), 152–163. doi: 10.3171/2013.9.JNS13839.CrossRefPubMedGoogle Scholar
  72. Yang, J. C., Papadimitriou, G., Eckbo, R., Yeterian, E. H., Liang, L., Dougherty, D. D., et al. (2015). Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy. Brain Imaging and Behavior, 9(2), 342–352. doi: 10.1007/s11682-014-9314-z.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Yeterian, E. H., & Pandya, D. N. (1988). Corticothalamic connections of paralimbic regions in the rhesus monkey. Journal of Comparative Neurology, 269(1), 130–146. doi: 10.1002/cne.902690111.CrossRefPubMedGoogle Scholar
  74. Yeterian, E. H., & Pandya, D. N. (1994). Laminar origin of striatal and thalamic projections of the prefrontal cortex in rhesus monkeys. Experimental Brain Research, 99(3), 383–398.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Nikolaos Makris
    • 1
    • 2
    • 3
    • 4
    Email author
  • Yogesh Rathi
    • 1
    • 2
  • Palig Mouradian
    • 1
  • Giorgio Bonmassar
    • 1
  • George Papadimitriou
    • 1
  • Wingkwai I. Ing
    • 1
  • Edward H. Yeterian
    • 5
  • Marek Kubicki
    • 1
    • 2
  • Emad N. Eskandar
    • 1
  • Lawrence L. Wald
    • 1
  • Qiuyun Fan
    • 1
  • Aapo Nummenmaa
    • 1
  • Alik S. Widge
    • 1
    • 6
  • Darin D. Dougherty
    • 1
  1. 1.Departments of Psychiatry, Neurology, Neurosurgery and Radiology, Center for Morphometric Analysis, Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestownUSA
  2. 2.Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.McLean Imaging Center, McLean HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of Anatomy and NeurobiologyBoston University School of MedicineBostonUSA
  5. 5.Department of PsychologyColby CollegeWatervilleUSA
  6. 6.Picower Institute for Learning & MemoryMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations