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Diffusion imaging-based subdivision of the human hypothalamus: a magnetic resonance study with clinical implications

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Abstract

The hypothalamus and its subdivisions are involved in many neuropsychiatric conditions such as affective disorders, schizophrenia, or narcolepsy, but parcellations of hypothalamic subnuclei have hitherto been feasible only with histological techniques in postmortem brains. In an attempt to map subdivisions of the hypothalamus in vivo, we analyzed the directionality information from high-resolution diffusion-weighted magnetic resonance images of healthy volunteers. We acquired T1-weighted and diffusion-weighted scans in ten healthy subjects at 3 T. In the T1-weighted images, we manually delineated an individual mask of the hypothalamus in each subject and computed in the co-registered diffusion-weighted images the similarity of the principal diffusion direction for each pair of mask voxels. By clustering the similarity matrix into three regions with a k-means algorithm, we obtained an anatomically coherent arrangement of subdivisions across hemispheres and subjects. In each hypothalamus mask, we found an anterior region with dorsoventral principal diffusion direction, a posteromedial region with rostro-caudal direction, and a lateral region with mediolateral direction. A comparative analysis with microstructural hypothalamus parcellations from the literature reveals that each of these regions corresponds to a specific group of hypothalamic subnuclei as defined in postmortem brains. This is to our best knowledge the first in vivo study that attempts a delineation of hypothalamic subdivisions by clustering diffusion-weighted magnetic resonance imaging data. When applied in a larger sample of neuropsychiatric patients, a structural analysis of hypothalamic subnuclei should contribute to a better understanding of the pathogenesis of neuropsychiatric conditions such as affective disorders.

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References

  1. Alsop DC (1997) The sensitivity of low flip angle RARE imaging. Magn Reson Med 37:176–184

    Article  PubMed  CAS  Google Scholar 

  2. Bao AM, Meynen G, Swaab DF (2008) The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 57:531–553

    Article  PubMed  CAS  Google Scholar 

  3. Baroncini M, Jissendi P, Balland E, Besson P, Pruvo JP, Francke JP, Dewailly D, Blond S, Prevot V (2012) MRI atlas of the human hypothalamus. Neuroimage 59:168–180

    Article  PubMed  Google Scholar 

  4. Baumann B, Bogerts B (2001) Neuroanatomical studies on bipolar disorder. Br J Psychiatry 178:S142–S147

    Article  PubMed  Google Scholar 

  5. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system: a technical review. NMR Biomed 15:435–455

    Article  PubMed  Google Scholar 

  6. Bernstein HG, Keilhoff G, Steiner J, Dobrowolny H, Bogerts B (2010) The hypothalamus in schizophrenia research: no longer a wallflower existence. Open Neuroendocrinol J 3:59–67

    Article  CAS  Google Scholar 

  7. Bernstein HG, Klix M, Dobrowolny H, Brisch R, Steiner J, Bielau H, Gos T, Bogerts B (2012) A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders. Eur Arch Psychiatry Clin Neurosci 262:637–646

    Article  PubMed  Google Scholar 

  8. Besseling RMH, Jansen JFA, Overvliet GM, Vaessen MJ, Braakman HMH, Hofman PAM, Aldenkamp AP, Backes WH (2012) Tract specific reproducibility of tractography based morphology and diffusion metrics. PLoS One 7:e34125

    Article  PubMed  CAS  Google Scholar 

  9. Bielau H, Trübner K, Krell D, Agelink MW, Bernstein HG, Stauch R, Mawrin C, Danos P, Gerhard L, Bogerts B, Baumann B (2005) Volume deficits of subcortical nuclei in mood disorders: a postmortem study. Eur Arch Psychiatry Clin Neurosci 255:401–412

    Article  PubMed  Google Scholar 

  10. Braak H, Braak E (1987) The hypothalamus of the human adult: chiasmatic region. Anat Embryol (Berl) 175:315–330

    Article  CAS  Google Scholar 

  11. Braak H, Braak E (1992) Anatomy of the human hypothalamus (chiasmatic and tuberal region). In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) Progress in brain research. Elsevier, Amsterdam, pp 3–16

    Google Scholar 

  12. Busse S, Bernstein HG, Busse M, Bielau H, Brisch R, Mawrin C, Müller S, Sarnyai Z, Gos T, Bogerts B, Steiner J (2012) Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: a potential link to impaired growth factor signaling and energy homeostasis. Eur Arch Psychiatry Clin Neurosci 262:365–374

    Article  PubMed  Google Scholar 

  13. Crosby EC, Woodburne RT (1939) The comparative anatomy of the preoptic area and the hypothalamus. Res Publ Assoc Res Nerv Ment Dis 20:52–169

    Google Scholar 

  14. Doran M, Hajnal JV, Van Bruggen N, King MD, Young IR, Bydder GM (1990) Normal and abnormal white matter tracts shown by MR imaging using directional diffusion weighted sequences. J Comput Assist Tomogr 14:865–873

    Article  PubMed  CAS  Google Scholar 

  15. Draganski B, Geisler P, Hajak G, Schuierer G, Bogdahn U, Winkler J, May A (2002) Hypothalamic gray matter changes in narcoleptic patients. Nat Med 8:1186–1188

    Article  PubMed  CAS  Google Scholar 

  16. Drevets WC, Price JL, Furey ML (2008) Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct 213:93–118

    Article  PubMed  Google Scholar 

  17. Dupont RM, Jernigan TL, Heindel W, Butters N, Shafer K, Wilson T, Hesselink J, Gillin JC (1995) Magnetic resonance imaging and mood disorders: localization of white matter and other subcortical abnormalities. Arch Gen Psychiatry 52:747–755

    Article  PubMed  CAS  Google Scholar 

  18. Georgiadis JR, Farrell MJ, Boessen R, Denton DA, Gavrilescu M, Kortekaas R, Renken RJ, Hoogduin JM, Egan GF (2010) Dynamic subcortical blood flow during male sexual activity with ecological validity: a perfusion fMRI study. Neuroimage 50:208–216

    Article  PubMed  Google Scholar 

  19. Geyer S, Weiss M, Reimann K, Lohmann G, Turner R (2011) Microstructural parcellation of the human cerebral cortex: from Brodmann’s post-mortem map to in vivo mapping with high-field magnetic resonance imaging. Front Hum Neurosci 5:19

    Article  PubMed  Google Scholar 

  20. Goldstein JM, Seidman LJ, Makris N, Ahern T, O’Brien LM, Caviness VS, Kennedy DN, Faraone SV, Tsuang MT (2007) Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability. Biol Psychiatry 61:935–945

    Article  PubMed  CAS  Google Scholar 

  21. Griswold MA, Jakob PM, Heidemann RM, Nittka M, Jellus V, Wang J, Kiefer B, Haase A (2002) Generalized autocalibrating partially parallel acquisitions (GRAPPA). Magn Reson Med 47:1202–1210

    Article  PubMed  Google Scholar 

  22. Hegerl U, Wilk K, Olbrich S, Schoenknecht P, Sander C (2012) Hyperstable regulation of vigilance in patients with major depressive disorder. World J Biol Psychiatry 13:436–446

    Article  PubMed  Google Scholar 

  23. Hofman MA, Swaab DF (1992) The human hypothalamus: comparative morphometry and photoperiodic influences. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) Progress in brain research. Elsevier, Amsterdam, pp 133–149

    Google Scholar 

  24. Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17:825–841

    Article  PubMed  Google Scholar 

  25. Jenkinson M, Beckmann CF, Behrens TEJ, Woolrich MW, Smith SM (2012) FSL. Neuroimage 62:782–790

    Article  PubMed  Google Scholar 

  26. Johansen-Berg H, Behrens TEJ, Robson MD, Drobnjak I, Rushworth MFS, Brady JM, Smith SM, Higham DJ, Matthews PM (2004) Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. Proc Natl Acad Sci USA 101:13335–13340

    Article  PubMed  CAS  Google Scholar 

  27. Johansen-Berg H, Behrens TEJ, Sillery E, Ciccarelli O, Thompson AJ, Smith SM, Matthews PM (2005) Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb Cortex 15:31–39

    Article  PubMed  Google Scholar 

  28. Jones DK, Knösche TR, Turner R (2012) White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. Neuroimage. doi:10.1016/j.neuroimage.2012.06.081

    Google Scholar 

  29. Klein JC, Behrens TEJ, Robson MD, Mackay CE, Higham DJ, Johansen-Berg H (2007) Connectivity-based parcellation of human cortex using diffusion MRI: establishing reproducibility, validity and observer independence in BA 44/45 and SMA/pre-SMA. Neuroimage 34:204–211

    Article  PubMed  Google Scholar 

  30. Koutcherov Y, Mai JK, Paxinos G (2003) Hypothalamus of the human fetus. J Chem Neuroanat 26:253–270

    Article  PubMed  CAS  Google Scholar 

  31. Kwon HG, Byun WM, Ahn SH, Son SM, Jang SH (2011) The anatomical characteristics of the stria terminalis in the human brain: a diffusion tensor tractography study. Neurosci Lett 500:99–102

    Article  PubMed  CAS  Google Scholar 

  32. Le Bihan D (2003) Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci 4:469–480

    Article  PubMed  Google Scholar 

  33. Le Gros Clark WE (1936) The topography and homologies of the hypothalamic nuclei in man. J Anat 70:203–214

    Google Scholar 

  34. Le Gros Clark WE (1938) Morphological aspects of the hypothalamus. In: Le Gros Clark WE, Beattie J, Riddoch G, Dott NM (eds) The hypothalamus: morphological, functional, clinical and surgical aspects. Oliver and Boyd, Edinburgh, pp 1–68

  35. Le Roux P, Hinks RS (1993) Stabilization of echo amplitudes in FSE sequences. Magn Reson Med 30:183–190

    Article  PubMed  Google Scholar 

  36. Lemaire JJ, Frew AJ, McArthur D, Gorgulho AA, Alger JR, Salomon N, Chen C, Behnke EJ, De Salles AAF (2011) White matter connectivity of human hypothalamus. Brain Res 1371:43–64

    Article  PubMed  CAS  Google Scholar 

  37. Li M, He HG, Shi W, Li J, Lv B, Wang CH, Miao QW, Wang ZC, Wang NL, Walter M, Sabel BA (2012) Quantification of the human lateral geniculate nucleus in vivo using MR imaging based on morphometry: volume loss with age. Am J Neuroradiol 33:915–921

    Article  PubMed  CAS  Google Scholar 

  38. Luppino G, Matelli M, Camarda R, Rizzolatti G (1993) Corticocortical connections of area F3 (SMA-proper) and area F6 (pre-SMA) in the macaque monkey. J Comp Neurol 338:114–140

    Article  PubMed  CAS  Google Scholar 

  39. Mai JK, Paxinos G, Voss T (2008) Atlas of the human brain, 3rd edn. Elsevier, Academic Press, Amsterdam

    Google Scholar 

  40. Marques JP, Kober T, Krueger G, van der Zwaag W, van de Moortele PF, Gruetter R (2010) MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. Neuroimage 49:1271–1281

    Article  PubMed  Google Scholar 

  41. Matelli M, Luppino G (1996) Thalamic input to mesial and superior area 6 in the macaque monkey. J Comp Neurol 372:59–87

    Article  PubMed  CAS  Google Scholar 

  42. Moseley ME, Cohen Y, Kucharczyk J, Mintorovitch J, Asgari HS, Wendland MF, Tsuruda J, Norman D (1990) Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 176:439–445

    PubMed  CAS  Google Scholar 

  43. Mugler JP, Brookeman JR (1990) Three-dimensional magnetization-prepared rapid gradient-echo imaging (3D MP RAGE). Magn Reson Med 15:152–157

    Article  PubMed  Google Scholar 

  44. Nanetti L, Cerliani L, Gazzola V, Renken R, Keysers C (2009) Group analyses of connectivity-based cortical parcellation using repeated k-means clustering. Neuroimage 47:1666–1677

    Article  PubMed  Google Scholar 

  45. Nieuwenhuys R, Voogd J, van Huijzen C (2008) The human central nervous system, 4th edn. Springer, Berlin

    Google Scholar 

  46. Pinilla BP (2009) Auswirkungen der unipolar depressiven Störung auf strukturelle Gehirnveränderungen in der Voxel-based-NMR-Morphometry und auf “hippocampusspezifische” kognitive Leistungen. Dissertation, Charité, Berlin

  47. Price JL, Drevets WC (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology 35:192–216

    Article  PubMed  Google Scholar 

  48. Reese TG, Heid O, Weisskoff RM, Wedeen VJ (2003) Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magn Reson Med 49:177–182

    Article  PubMed  CAS  Google Scholar 

  49. Rizzolatti G, Luppino G, Matelli M (1996) The classic supplementary motor area is formed by two independent areas. In: Lüders HO (ed) Supplementary sensorimotor area. Lippincott-Raven, Philadelphia, pp 45–56

    Google Scholar 

  50. Saeki N, Kansaku K, Higuchi Y, Kawano K, Iijima T, Inoue N, Yamaura A (2001) Demonstration of the post commissural fibres of the fornix in short-inversion time inversion-recovery imaging on a high-field system. Neuroradiology 43:547–550

    Article  PubMed  CAS  Google Scholar 

  51. Saper CB (2012) Hypothalamus. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Elsevier, Academic Press, Amsterdam, pp 548–583

    Chapter  Google Scholar 

  52. Schindler S, Geyer S, Strauß M, Anwander A, Hegerl U, Turner R, Schönknecht P (2012) Structural studies of the hypothalamus and its nuclei in mood disorders. Psychiatry Res 201:1–9

    Article  PubMed  Google Scholar 

  53. Schmidt FM, Brügel M, Kratzsch J, Strauß M, Sander C, Baum P, Thiery J, Hegerl U, Schönknecht P (2010) Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls. Neurosci Lett 483:20–22

    Article  PubMed  CAS  Google Scholar 

  54. Schmidt FM, Arendt E, Steinmetzer A, Bruegel M, Kratzsch J, Strauß M, Baum P, Hegerl U, Schönknecht P (2011) CSF-hypocretin-1 levels in patients with major depressive disorder compared to healthy controls. Psychiatry Res 190:240–243

    Article  PubMed  CAS  Google Scholar 

  55. Schoenknecht P, Olbrich S, Sander C, Spindler P, Hegerl U (2010) Treatment of acute mania with modafinil monotherapy. Biol Psychiatry 67:e55–e57

    Article  PubMed  Google Scholar 

  56. Solano-Castiella E, Anwander A, Lohmann G, Weiss M, Docherty C, Geyer S, Reimer E, Friederici AD, Turner R (2010) Diffusion tensor imaging segments the human amygdala in vivo. Neuroimage 49:2958–2965

    Article  PubMed  Google Scholar 

  57. Stephan H, Frahm H, Baron G (1981) New and revised data on volumes of brain structures in insectivores and primates. Folia Primatol (Basel) 35:1–29

    Article  CAS  Google Scholar 

  58. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. 3-Dimensional proportional system: an approach to cerebral imaging. Thieme, Stuttgart

  59. Toni R, Malaguti A, Benfenati F, Martini L (2004) The human hypothalamus: a morpho-functional perspective. J Endocrinol Invest 27:73–94

    PubMed  CAS  Google Scholar 

  60. Walter M, Bermpohl F, Mouras H, Schiltz K, Tempelmann C, Rotte M, Heinze HJ, Bogerts B, Northoff G (2008) Distinguishing specific sexual and general emotional effects in fMRI: subcortical and cortical arousal during erotic picture viewing. Neuroimage 40:1482–1494

    Article  PubMed  Google Scholar 

  61. Wiegell MR, Tuch DS, Larsson HBW, Wedeen VJ (2003) Automatic segmentation of thalamic nuclei from diffusion tensor magnetic resonance imaging. Neuroimage 19:391–401

    Article  PubMed  Google Scholar 

  62. Young JK, Stanton GB (1994) A three-dimensional reconstruction of the human hypothalamus. Brain Res Bull 35:323–327

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Part of this work was supported by the FET project CONNECT of the European Union (http://www.brain-connect.eu).

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany

    Peter Schönknecht, Friederike Petzold, Stephanie Schindler & Ulrich Hegerl

  2. Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103, Leipzig, Germany

    Alfred Anwander, Thomas R. Knösche, Harald E. Möller, Robert Turner & Stefan Geyer

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  1. Peter Schönknecht
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  2. Alfred Anwander
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  3. Friederike Petzold
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  4. Stephanie Schindler
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  6. Harald E. Möller
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  7. Ulrich Hegerl
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  8. Robert Turner
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  9. Stefan Geyer
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Correspondence to Peter Schönknecht.

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Schönknecht, P., Anwander, A., Petzold, F. et al. Diffusion imaging-based subdivision of the human hypothalamus: a magnetic resonance study with clinical implications. Eur Arch Psychiatry Clin Neurosci 263, 497–508 (2013). https://doi.org/10.1007/s00406-012-0389-5

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  • DOI: https://doi.org/10.1007/s00406-012-0389-5

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