Journal of Computational Neuroscience

, Volume 28, Issue 3, pp 425–441 | Cite as

Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation

Article

Abstract

Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson’s disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms. A least mean square error training algorithm was developed to parameterize network connections and minimize error when compared to experimental spike and burst rates in the parkinsonian condition. The output of the trained network was then compared to experimental data not used in the training process. We found that reducing the influence of the cortical beta input on the model generated activity that agreed well with recordings from normal monkeys. Further, during STN DBS in the parkinsonian condition the simulations reproduced the reduction in GPi bursting found in existing experimental data. The model also provided the opportunity to greatly expand analysis of GPi bursting activity, generating three major predictions. First, its reduction was proportional to the volume of STN activated by DBS. Second, GPi bursting decreased in a stimulation frequency dependent manner, saturating at values consistent with clinically therapeutic DBS. And third, ablating STN neurons, reported to generate similar therapeutic outcomes as STN DBS, also reduced GPi bursting. Our theoretical analysis of stimulation induced network activity suggests that regularization of GPi firing is dependent on the volume of STN tissue activated and a threshold level of burst reduction may be necessary for therapeutic effect.

Keywords

Subthalamic nucleus Globus pallidus Basal ganglia Oscillation Burst 

References

  1. Alvarez, L., Macias, R., Pavon, N., Lopez, G., Rodriguez-Oroz, M. C., Rodriguez, R., et al. (2009). Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months. Journal of Neurology, Neurosurgery and Psychiatry, 80, 979–985.CrossRefGoogle Scholar
  2. Bekar, L., Libionka, W., Tian, G. F., Xu, Q., Torres, A., Wang, X., et al. (2008). Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nature Medicine, 14, 75–80.CrossRefPubMedGoogle Scholar
  3. Bergman, H., Wichmann, T., Karmon, B., & DeLong, M. R. (1994). The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. Journal of Neurophysiology, 72, 507–520.PubMedGoogle Scholar
  4. Bevan, M. D., Magill, P. J., Terman, D., Bolam, J. P., & Wilson, C. J. (2002). Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends in Neurosciences, 25(10), 525–31.CrossRefPubMedGoogle Scholar
  5. Birdno, M. J., Kuncel, A. M., Dorval, A. D., Turner, D. A., & Grill, W. M. (2008). Tremor varies as a function of the temporal regularity of deep brain stimulation. NeuroReport, 19, 599–602.CrossRefPubMedGoogle Scholar
  6. Brown, P. (2000). Cortical drives to human muscle: the Piper and related rhythms. Progress in Neurobiology, 60, 97–108.CrossRefPubMedGoogle Scholar
  7. Brown, P., & Williams, D. (2005). Basal ganglia local field potential activity: character and functional significance in the human. Clinical Neurophysiology, 116, 2510–2519.CrossRefPubMedGoogle Scholar
  8. Brown, P., Oliviero, A., Mazzone, P., Insola, A., Tonali, P., & Di Lazzaro, V. (2001). Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease. Journal of Neuroscience, 21, 1033–1038.PubMedGoogle Scholar
  9. Butson, C. R., Cooper, S. E., Henderson, J. M., & McIntyre, C. C. (2007). Patient-specific analysis of the volume of tissue activated during deep brain stimulation. Neuroimage, 34, 661–670.CrossRefPubMedGoogle Scholar
  10. Carnevale, N. T., Hines, M. L. (2005). The Neuron book. Cambridge University Press.Google Scholar
  11. Cooper, A. J., & Stanford, I. M. (2000). Electrophysiological and morphological characteristics of three subtypes of rat globus pallidus neurone in vitro. Journal of Physiology, 527(Pt 2), 291–304.CrossRefPubMedGoogle Scholar
  12. Courtemanche, R., Fujii, N., & Graybiel, A. M. (2003). Synchronous, focally modulated beta-band oscillations characterize local field potential activity in the striatum of awake behaving monkeys. Journal of Neuroscience, 23, 11741–11752.PubMedGoogle Scholar
  13. Dejean, C., Gross, C. E., Bioulac, B., & Boraud, T. (2008). Dynamic changes in the cortex-basal ganglia network after dopamine depletion in the rat. Journal of Neurophysiology, 100, 385–396.CrossRefPubMedGoogle Scholar
  14. Destexhe, A., Mainen, Z. F., & Sejnowski, T. J. (1994a). An efficient method for computing synaptic conductances based on a kinetic model of receptor binding. Neural Computation, 6, 10–14.CrossRefGoogle Scholar
  15. Destexhe, A., Mainen, Z. F., & Sejnowski, T. J. (1994b). Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. Journal of Computational Neuroscience, 1, 195–230.CrossRefGoogle Scholar
  16. Feng, X. J., Greenwald, B., Rabitz, H., Shea-Brown, E., & Kosut, R. (2007). Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: concepts and lessons from a computational model. Journal of Neural Engineering, 4, L14–L21.CrossRefPubMedGoogle Scholar
  17. Galvan, A., & Wichmann, T. (2008). Pathophysiology of parkinsonism. Clinical Neurophysiology, 119, 1459–1474.CrossRefPubMedGoogle Scholar
  18. Goldberg, J. A., Kats, S. S., & Jaeger, D. (2003). Globus pallidus discharge is coincident with striatal activity during global slow wave activity in the rat. Journal of Neuroscience, 23, 10058–10063.PubMedGoogle Scholar
  19. Goldberg, J. A., Rokni, U., Boraud, T., Vaadia, E., & Bergman, H. (2004). Spike synchronization in the cortex/basal-ganglia networks of Parkinsonian primates reflects global dynamics of the local field potentials. Journal of Neuroscience, 24, 6003–6010.CrossRefPubMedGoogle Scholar
  20. Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, J. M., & Deisseroth, K. (2009). Optical deconstruction of parkinsonian neural circuitry. Science, 324, 354–359.CrossRefPubMedGoogle Scholar
  21. Guo, Y., Rubin, J. E., McIntyre, C. C., Vitek, J. L., & Terman, D. (2008). Thalamocortical relay fidelity varies across subthalamic nucleus deep brain stimulation protocols in a data-driven computational model. Journal of Neurophysiology, 99, 1477–1492.CrossRefPubMedGoogle Scholar
  22. Hahn, P. J., Russo, G. S., Hashimoto, T., Miocinovic, S., Xu, W., McIntyre, C. C., et al. (2008). Pallidal burst activity during therapeutic deep brain stimulation. Experimental Neurology, 211, 243–251.CrossRefPubMedGoogle Scholar
  23. Hammond, C., Bergman, H., & Brown, P. (2007). Pathological synchronization in Parkinson's disease: networks, models and treatments. Trends in Neurosciences, 30, 357–364.CrossRefPubMedGoogle Scholar
  24. Hardman, C. D., Henderson, J. M., Finkelstein, D. I., Horne, M. K., Paxinos, G., & Halliday, G. M. (2002). Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: volume and neuronal number for the output, internal relay, and striatal modulating nuclei. Journal of Comparative Neurology, 445, 238–255.CrossRefPubMedGoogle Scholar
  25. Hashimoto, T., Elder, C. M., Okun, M. S., Patrick, S. K., & Vitek, J. L. (2003). Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. Journal of Neuroscience, 23, 1916–1923.PubMedGoogle Scholar
  26. Humphries, M. D., Stewart, R. D., & Gurney, K. N. (2006). A physiologically plausible model of action selection and oscillatory activity in the basal ganglia. Journal of Neuroscience, 26, 12921–12942.CrossRefPubMedGoogle Scholar
  27. Kuhn, A. A., Trottenberg, T., Kivi, A., Kupsch, A., Schneider, G. H., & Brown, P. (2005). The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease. Experimental Neurology, 194, 212–220.CrossRefPubMedGoogle Scholar
  28. Leblois, A., Boraud, T., Meissner, W., Bergman, H., & Hansel, D. (2006). Competition between feedback loops underlies normal and pathological dynamics in the basal ganglia. Journal of Neuroscience, 26, 3567–3583.CrossRefPubMedGoogle Scholar
  29. Li, S., Arbuthnott, G. W., Jutras, M. J., Goldberg, J. A., & Jaeger, D. (2007). Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. Journal of Neurophysiology, 98, 3525–3537.CrossRefPubMedGoogle Scholar
  30. Magnin, M., Morel, A., & Jeanmonod, D. (2000). Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience, 96, 549–564.CrossRefPubMedGoogle Scholar
  31. Maks, C. B., Butson, C. R., Walter, B. L., Vitek, J. L., & McIntyre, C. C. (2009). Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes. Journal of Neurology, Neurosurgery and Psychiatry, 80, 659–666.CrossRefGoogle Scholar
  32. McIntyre, C. C., & Hahn, P. J. (2010). Network perspectives on the mechanisms of deep brain stimulation. Neurobiology of Disease. doi:10.1016/j.nbd.2009.09.022.PubMedGoogle Scholar
  33. Mink, J. W. (1996). The basal ganglia: focused selection and inhibition of competing motor programs. Progress in Neurobiology, 50, 381–425.CrossRefPubMedGoogle Scholar
  34. Mink, J. W., & Thach, W. T. (1993). Basal ganglia intrinsic circuits and their role in behavior. Current Opinion in Neurobiology, 3, 950–957.CrossRefPubMedGoogle Scholar
  35. Miocinovic, S., Parent, M., Butson, C. R., Hahn, P. J., Russo, G. S., Vitek, J. L., et al. (2006). Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation. Journal of Neurophysiology, 96, 1569–1580.CrossRefPubMedGoogle Scholar
  36. Modolo, J., Henry, J., & Beuter, A. (2008). Dynamics of the Subthalamo-pallidal Complex in Parkinson's Disease During Deep Brain Stimulation. Journal of biological physics, 34, 251–266.CrossRefPubMedGoogle Scholar
  37. Montgomery, E. B., Jr., & Baker, K. B. (2000). Mechanisms of deep brain stimulation and future technical developments. Neurological Research, 22, 259–266.PubMedGoogle Scholar
  38. Nambu, A., & Llinas, R. (1994). Electrophysiology of globus pallidus neurons in vitro. Journal of Neurophysiology, 72, 1127–1139.PubMedGoogle Scholar
  39. Nandhagopal, R., McKeown, M. J., & Stoessl, A. J. (2008). Functional imaging in Parkinson disease. Neurology, 70, 1478–1488.CrossRefPubMedGoogle Scholar
  40. Nini, A., Feingold, A., Slovin, H., & Bergman, H. (1995). Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism. Journal of Neurophysiology, 74, 1800–1805.PubMedGoogle Scholar
  41. Otsuka, T., Abe, T., Tsukagawa, T., & Song, W. J. (2004). Conductance-based model of the voltage-dependent generation of a plateau potential in subthalamic neurons. Journal of Neurophysiology, 92, 255–264.CrossRefPubMedGoogle Scholar
  42. Phillips, M. D., Baker, K. B., Lowe, M. J., Tkach, J. A., Cooper, S. E., Kopell, B. H., et al. (2006). Parkinson disease: pattern of functional MR imaging activation during deep brain stimulation of subthalamic nucleus–initial experience. Radiology, 239, 209–216.CrossRefPubMedGoogle Scholar
  43. Plenz, D., & Kital, S. T. (1999). A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature, 400, 677–682.CrossRefPubMedGoogle Scholar
  44. Press, W. H., Teukolsky, S. A., Vetterling, W. T., Flannery, B. P. (1992). Numerical recipes in C, The art of scientific computing, 2nd edition. Cambridge University Press.Google Scholar
  45. Raz, A., Vaadia, E., & Bergman, H. (2000). Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine vervet model of parkinsonism. Journal of Neuroscience, 20, 8559–8571.PubMedGoogle Scholar
  46. Rizzone, M., Lanotte, M., Bergamasco, B., Tavella, A., Torre, E., Faccani, G., et al. (2001). Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters. Journal of Neurology, Neurosurgery and Psychiatry, 71, 215–219.CrossRefGoogle Scholar
  47. Rubchinsky, L. L., Kopell, N., & Sigvardt, K. A. (2003). Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalamic nucleus-pallidal circuits. Proc Natl Acad Sci USA, 100, 14427–14432.CrossRefPubMedGoogle Scholar
  48. Rubin, J. E., & Terman, D. (2004). High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model. Journal of Computational Neuroscience, 16, 211–235.CrossRefPubMedGoogle Scholar
  49. Sharott, A., Magill, P. J., Bolam, J. P., & Brown, P. (2005a). Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat. Journal of Physiology, 562, 951–963.CrossRefGoogle Scholar
  50. Sharott, A., Magill, P. J., Harnack, D., Kupsch, A., Meissner, W., & Brown, P. (2005b). Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat. European Journal of Neuroscience, 21, 1413–1422.CrossRefGoogle Scholar
  51. Shils, J. L., Mei, L. Z., & Arle, J. E. (2008). Modeling parkinsonian circuitry and the DBS electrode. II. Evaluation of a computer simulation model of the basal ganglia with and without subthalamic nucleus stimulation. Stereotactic and Functional Neurosurgery, 86, 16–29.CrossRefPubMedGoogle Scholar
  52. Soares, J., Kliem, M. A., Betarbet, R., Greenamyre, J. T., Yamamoto, B., & Wichmann, T. (2004). Role of external pallidal segment in primate parkinsonism: comparison of the effects of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment. Journal of Neuroscience, 24, 6417–6426.CrossRefPubMedGoogle Scholar
  53. Tass, P. A. (2003). A model of desynchronizing deep brain stimulation with a demand-controlled coordinated reset of neural subpopulations. Biological Cybernetics, 89, 81–88.CrossRefPubMedGoogle Scholar
  54. Terman, D., Rubin, J. E., Yew, A. C., & Wilson, C. J. (2002). Activity patterns in a model for the subthalamopallidal network of the basal ganglia. Journal of Neuroscience, 22, 2963–2976.PubMedGoogle Scholar
  55. Wichmann, T., & Soares, J. (2006). Neuronal firing before and after burst discharges in the monkey basal ganglia is predictably patterned in the normal state and altered in parkinsonism. Journal of Neurophysiology, 95, 2120–2133.CrossRefPubMedGoogle Scholar
  56. Wichmann, T., Bergman, H., Starr, P. A., Subramanian, T., Watts, R. L., & DeLong, M. R. (1999). Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates. Experimental Brain Research, 125, 397–409.CrossRefGoogle Scholar
  57. Xu, W., Russo, G. S., Hashimoto, T., Zhang, J., & Vitek, J. L. (2008). Subthalamic nucleus stimulation modulates thalamic neuronal activity. J Neurosci, 28, 11916–11924.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringCleveland Clinic FoundationClevelandUSA

Personalised recommendations