Deep brain stimulation (DBS) is a non-pharmacological treatment for Parkinson’s disease (PD), and its efficacy depends largely on which anatomical structure (target) is stimulated. The subthalamic nucleus (STN) is one of the most commonly used targets, but stimulation of new targets within the posterior sub-thalamic area (PSA), comprising a group of white matter fibers known as prelemniscal radiations (Raprl), as well as the caudal zonaincerta nucleus (Zic), have proven to be superior at improving certain clinical symptoms. Despite their clinical usefulness, their anatomical connectivity has not been completely described in humans. We performed constrained sphe rical deconvolution of the signal in diffusion- weighted images and subsequent tractography as a means to non-invasively define the connectivity of the Raprl and Zic in a group of five patients with PD. Further, we used track-density imaging, a novel method to improve the spatial resolution of the acquired images, in order to visualize the small subregions that comprise the PSA with a voxel resolution of 0.2 × 0.2 × 0.2 mm 3 . Both Raprl and Zic demonstrated high probability of connectivity with the dorsal brainstem, cerebellum, subcortical nuclei (globus pallidum ventral, lateral thalamic nuclei), and cortical areas (orbitofrontal cortex, primary and supplementary motor cortex areas). The connectivity patterns were re-producible between patients and were discretely organized as the tracts entered/exited the PSA, depending on their end points. These findings indicate that the PSA is part of the neuronal circuitry controlling movement, and the precise characterization of its connectivity will aid in our understanding of the net-works involved in PD and how they can be modulated with DBS in order to alleviate symptoms.
KeywordsParkinson Disease (PD)Posterior Subthalamic Area (PSA)TractographyTrack-Density Images (TDI)
Benabid, A.L., Pollak, P., Louveau, A., Henry, S. and De Rougemont, J. (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Applied Neurophysiology, 50, 344-346.
Velasco, F.C., Molina-Negro, P., Bertrand, C. and Hardy, J. (1972) Further definition of the subthalamic target for arrest of tremor. Journal of Neurosurgery, 36, 184-191. doi:10.3171/jns.1972.36.2.0184
Kitagawa, M., Murata, J., Uesugi, H., Kikuchi, S., Saito, H., Tashiro, K. and Sawamura, Y. (2005) Two-year follow-up of chronic stimulation of the posterior subthalamic white matter for tremor-dominant Parkinson’s disease. Neurosurgery, 56, 281-289; discussion 281-289. doi:10.1227/01.NEU.0000148167.49105.A3
Plaha, P., Ben-Shlomo, Y., Patel, N.K. and Gill, S.S. (2006) Stimulation of the caudal zonaincerta is superior to stimulation of the subthalamic nucleus in improving contralateral Parkinsonism. Brain, 129, 1732-1747. doi:10.1093/brain/awl127
Carrillo-Ruiz, J.D., Velasco, F., Jiménez, F., Castro, G., Velasco, A.L., Hernández, J.A., Ceballos, J. and Velasco, M. (2008) Bilateral electrical stimulation of prelemniscal radiations in the treatment of advanced Parkinson’s disease. Neurosurgery, 62, 347-357; discussion 357-359. doi:10.1227/01.neu.0000316001.03765.e8
Velasco, F., Jiménez, F., Pérez, M.L., Carrillo-Ruiz, J.D., Velasco, A.L., Ceballos, J. and Velasco, M. (2001) Electrical stimulation of the prelemniscal radiation in the treatment of Parkinson’s disease: An old target revised with new techniques. Neurosurgery, 49, 293-306; discussion 306-308.
Plaha, P., Javed, S., Agombar, D., O’Farrell, G., Khan, S, Whone, A. and Gill, S. (2011) Bilateral caudal zonaincerta nucleus stimulation for essential tremor: Outcome and quality of life. Journal of Neurology, Neurosurgery & Psychiatry, 82, 899-904. doi:10.1136/jnnp.2010.222992
Velasco, F. and Velasco, M. (1979) A reticulothalamic system mediating proprioceptive attention and tremor in man. Neurosurgery, 4, 30-36. doi:10.1227/00006123-197901000-00006
Blomstedt, P., Sandvik, U., Fytagoridis, A. and Tisch, S. (2009) The posterior subthalamic area in the treatment of movement disorders: Past, present, and future. Neuro-surgery, 64, 1029-1038; discussion 1038-1042. doi:10.1227/01.NEU.0000345643.69486.BC
Brunenberg, E.J.L., Platel, B., Hofman, P.A.M., TerHaar Romeny, B.M. and Visser-Vandewalle, V. (2011) Magnetic resonance imaging techniques for visualization of the subthalamic nucleus. Journal of Neurosurgery, 115, 971-984. doi:10.3171/2011.6.JNS101571
Dormont, D., Ricciardi, K.G., Tandé, D., Parain, K., Menuel, C., Galanaud, D., Navarro, S., Cornu, P., Agid, Y. and Yelnik, J. (2004) Is the subthalamic nucleus hypointense on T2-weighted images? A correlation study using MR imaging and stereotactic atlas data. American Journal of Neuroradiology, 25, 1516-1523.
Slavin, K.V., Thulborn, K.R., Wess, C. and Nersesyan, H. (2006) Direct visualization of the human subthalamic nucleus with 3T MR imaging. American Journal of Neuroradiology, 27, 80-84.
Le Bihan, D. and Van Zijl, P. (2002) From the diffusion coefficient to the diffusion tensor. NMR in Biomedicine, 15, 431-434. doi:10.1002/nbm.798
Beaulieu, C. (2002) The basis of anisotropic water diffusion in the nervous system—A technical review. NMR in Biomedicine, 15, 435-455. doi:10.1002/nbm.782
Basser, P.J., Mattiello, J. and LeBihan, D. (1994) MR diffusion tensor spectroscopy and imaging. Biophysical Journal, 66, 259-267. doi:10.1016/S0006-3495(94)80775-1
Mori, S. and Van Zijl, P.C.M. (2002) Fiber tracking: principles and strategies—A technical review. NMR in Biomedicine, 15, 468-480. doi:10.1002/nbm.781
Behrens, T.E.J., Berg, H.J., Jbabdi, S., Rushworth, M.F.S. and Woolrich, M.W. (2007) Probabilistic diffusion trac-tography with multiple fibre orientations: What can we gain? Neuroimage, 34, 144-155. doi:10.1016/j.neuroimage.2006.09.018
Tournier, J.-D., Calamante, F. and Connelly, A. (2007) Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution. Neuroimage, 35, 1459- 1472. doi:10.1016/j.neuroimage.2007.02.016
Calamante, F., Tournier, J.-D., Jackson, G.D. and Connelly, A. (2010) Track-density imaging (TDI): Super- resolution white matter imaging using whole-brain track-density mapping. Neuroimage, 53, 1233-1243. doi:10.1016/j.neuroimage.2010.07.024
Calamante, F., Tournier, J.-D., Heidemann, R.M., Anwander, A., Jackson, G.D. and Connelly, A. (2011) Track density imaging (TDI): Validation of super resolution property. Neuroimage, 56, 1259-1266. doi:10.1016/j.neuroimage.2011.02.059
Calamante, F., Tournier, J.-D., Smith, R.E. and Connelly, A. (2012) A generalised framework for super-resolution track-weighted imaging. Neuroimage, 59, 2494-2503. doi:10.1016/j.neuroimage.2011.08.099
Leemans, A. and Jones, D.K. (2009) The B-matrix must be rotated when correcting for subject motion in DTI data. Magnetic Resonance in Medicine, 61, 1336-1349. doi:10.1002/mrm.21890
Smith, S.M. (2002) Fast robust automated brain extraction. Human Brain Mapping, 17, 143-155. doi:10.1002/hbm.10062
Tournier, J.-D., Calamante, F., Gadian, D.G. and Connelly, A. (2004) Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution. Neuroimage, 23, 1176-1185. doi:10.1016/j.neuroimage.2004.07.037
Parker, G.J.M. and Alexander, D.C. (2005) Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue. Philosophical Transactions of the Royal Society of London B Biological Sciences, 360, 893-902.
Morris, D.M., Embleton, K.V. and Parker, G.J.M. (2008) Probabilistic fibre tracking: Differentiation of connentions from chance events. Neuroimage, 42, 1329-1339. doi:10.1016/j.neuroimage.2008.06.012
Kerl, H.U., Gerigk, L., Huck, S., Al-Zghloul, M., Groden, C. and N?lte, I.S. (2012) Visualisation of the zonaincerta for deep brain stimulation at 3.0 Tesla. Clinical Neurora-diology, 22, 55-68. doi:10.1007/s00062-012-0136-3
Schaltenbrand, G. and Wahren, W. (1977) Atlas of stereo- taxy of the human brain. Thieme, Stuttgart.
Behrens, T.E.J., Johansen-Berg, H., Woolrich, M.W., Smith, S.M., Wheeler-Kingshott, C.A.M., Boulby, P.A., Barker, G.J., Sillery, E.L., Sheehan, K., Ciccarelli, O., Thompson, A.J., Brady, J.M. and Matthews, P.M. (2003) Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neuroscience, 6, 750-757. doi:10.1038/nn1075
Murata, J., Kitagawa, M., Uesugi, H., Saito, H., Iwasaki, Y., Kikuchi, S., Tashiro, K. and Sawamura, Y. (2003) Electrical stimulation of the posterior subthalamic area for the treatment of intractable proximal tremor. Journal of Neurosurgery, 99, 708-715. doi:10.3171/jns.2003.99.4.0708
Fytagoridis, A., Sandvik, U., Astr?m, M., Bergenheim, T. and Blomstedt, P. (2012) Long term follow-up of deep brain stimulation of the caudal zonaincerta for essential tremor. Journal of Neurology, Neurosurgery & Psychiatry, 83, 258-262. doi:10.1136/jnnp-2011-300765
Blomstedt, P., Fytagoridis, A., Astr?m, M., Linder, J., Forsgren, L. and Hariz, M.I. (2012) Unilateral caudal zonaincerta deep brain stimulation for Parkinsonian tremor. Parkinsonism and Related Disorders, 18, 1062-1066. doi:10.1016/j.parkreldis.2012.05.024
Carrillo-Ruiz, J.D., Velasco, F., Jimenez, F., Velasco, A.L., Castro, G., Soto, J. and Salcido, V. (2012) Prelemniscal radiations neuromodulation in Parkinson diseases treatment, topics in neuromodulation treatment. http://www.intechopen.com/books/topics-in-neuromodulation-treatment/prelemniscal-radiations-neuromodulation-in-the-treatment-of-parkinson-s-disease
Testut, L. (1947) Tratado de anatomía humana. Angio-logía-Sistema Nervioso Central, Segundo Tomo.
Yoshikawa, K., Nakata, Y., Yamada, K. and Nakagawa, M. (2004) Early pathological changes in the parkinsonian brain demonstrated by diffusion tensor MRI. Journal of Neurology, Neurosurgery & Psychiatry, 75, 481-484. doi:10.1136/jnnp.2003.021873
Chan, L.-L., Rumpel, H., Yap, K., Lee, E., Loo, H.-V., Ho, G.-L., Fook-Chong, S., Yuen, Y. and Tan, E.-K. (2007) Case control study of diffusion tensor imaging in Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 78, 1383-1386. doi:10.1136/jnnp.2007.121525
Menke, R.A., Scholz, J., Miller, K.L., Deoni, S., Jbabdi, S., Matthews, P.M. and Zarei, M. (2009) MRI characteristics of the substantianigra in Parkinson’s disease: A combined quantitative T1 and DTI study. Neuroimage, 47, 435-441. doi:10.1016/j.neuroimage.2009.05.017
Lambert, C., Zrinzo, L., Nagy, Z., Lutti, A., Hariz, M., Foltynie, T., Draganski, B., Ashburner, J. and Frackowiak, R. (2012) Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging. Neuro-image, 60, 83-94. doi:10.1016/j.neuroimage.2011.11.082
Du, G., Lewis, M.M., Styner, M., Shaffer, M.L., Sen, S., Yang, Q.X. and Huang, X. (2011) Combined R2* and diffusion tensor imaging changes in the substantianigra in Parkinson’s disease. Movement Disorders, 26, 1627-1632. doi:10.1002/mds.23643
Vaillancourt, D.E., Spraker, M.B., Prodoehl, J., Abraham, I., Corcos, D.M., Zhou, X.J., Comella, C.L. and Little, D.M. (2009) High-resolution diffusion tensor imaging in the substantianigra of de novo Parkinson disease. Neurology, 72, 1378-1384. doi:10.1212/01.wnl.0000340982.01727.6e
Brooks, D.J. (2010) Imaging approaches to Parkinson disease. Journal of Nuclear Medicine, 51, 596-609. doi:10.2967/jnumed.108.059998
Gattellaro, G., Minati, L., Grisoli, M., Mariani, C., Carella, F., Osio, M., Ciceri, E., Albanese, A. and Bruzzone, M.G. (2009) White matter involvement in idio-pathic Parkinson disease: A diffusion tensor imaging study. American Journal of Neuroradiology, 30, 1222-1226. doi:10.3174/ajnr.A1556
Sharman, M., Valabregue, R., Perlbarg, V., Marrakchi- Kacem, L., Vidailhet, M., Benali, H., Brice, A. and Lehéricy, S. (2012) Parkinson’s disease patients show reduced cortical-subcortical sensorimotor connectivity. Movement Disorders. doi:10.1002/mds.25255
Aravamuthan, B.R., Stein, J.F. and Aziz, T.Z. (2008) The anatomy and localization of the pedunculopontine nucleus determined using probabilistic diffusion tractography [corrected]. British Journal of Neurosurgery, 22, S25- S32. doi:10.1080/02688690802448251
Muthusamy, K.A., Aravamuthan, B.R., Kringelbach, M.L., Jenkinson, N., Voets, N.L., Johansen-Berg, H., Stein, J.F. and Aziz, T.Z. (2007) Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. Journal of Neurosurgery, 107, 814- 820. doi:10.3171/JNS-07/10/0814
Jiménez, F., Velasco, F., Carrillo-Ruiz, J.D., García, L., Madrigal, A., Velasco, A.L. and Márquez, I. (2006) Comparative evaluation of the effects of unilateral lesion versus electrical stimulation of the globuspallidusinternus in advanced Parkinson’s disease. Stereotactic and Functional Neurosurgery, 84, 64-71. doi:10.1159/000094034
Velasco, F., Palfi, S., Jimenez, J., Carrillo-Ruiz, J.D., Cas- tro, G. and Keravel, Y. (2009) Other targets to treat Parkinson disease posterior subthalamic targets and motor cortex. In: Lozano, A.M., Gildenberg, P.L. and Tasker, R.R., Eds, Spinger-Verlag, Berlin/Heidelberg, 1665-1678.
Velasco, F., Velasco, M., Ogarrio, C. and Olvera, A. (1986) Neglect induced by thalamotomy in humans: A quantitative appraisal of the sensory and motor deficits. Neurosurgery, 19, 744-751. doi:10.1227/00006123-198611000-00005
Velasco, F., Velasco, M., Jiménez, F., Velasco, A.L. and Salin-Pascual, R. (2005) Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders. Neurosurgery, 57, 439-448; discussion 439-448. doi:10.1227/01.NEU.0000172172.51818.51
Bejjani, B., Damier, P., Arnulf, I., Bonnet, A.M., Vidailhet, M., Dormont, D., Pidoux, B., Cornu, P., Marsault, C. and Agid, Y. (1997) Pallidal stimulation for Parkinson’s disease. Two targets? Neurology, 49, 1564-1569. doi:10.1212/WNL.49.6.1564
Krack, P., Pollak, P., Limousin, P., Hoffmann, D., Benazzouz, A., Le Bas, J.F., Koudsie, A. and Benabid, A.L. (1998) Opposite motor effects of pallidal stimulation in Parkinson’s disease. Annals of Neurology, 43, 180-192. doi:10.1002/ana.410430208
Collins, K.L., Lehmann, E.M. and Patil, P.G. (2010) Deep brain stimulation for movement disorders. Neurobiology of Disease, 38, 338-345. doi:10.1016/j.nbd.2009.11.019