Neurophysiology of the Basal Ganglia and Deep Brain Stimulation

  • Boran Urfalı
  • Yasin Temel
  • Hagai BergmanEmail author


Our understanding of the physiology of the basal ganglia and deep brain stimulation (DBS) has evolved and has been shaped by decades of studies of the basal ganglia in experimental animal models and human patients.

The classical models of the basal ganglia describe direct, indirect, and hyper-direct pathways connecting the cortex with the striatum and the basal ganglia output structures. The basal ganglia output nuclei modulate the excitability of the motor cortex. In Parkinson’s disease, dopamine depletion leads to reduced excitability of the motor cortex and akinesia. This model predicted increased activity in the subthalamic nucleus (STN) following dopamine depletion and suggested that the therapeutic effects of DBS are achieved through the restoration of normal STN discharge rate.

More recent computational models of the basal ganglia depict these as an actor/critic reinforcement learning network. The actor is the main axis of the basal ganglia connecting between all cortical areas encoding current state and the brain motor centers. The critic, or the teacher, is composed of midbrain dopaminergic neurons encoding the mismatch between predictions and reality. In this model, the main effect of dopamine is to modulate the efficacy of the cortico-striatal synapse. The efficacy of the cortico-striatal synapse dedicates the behavioral policy that is the coupling between state and action.

Finally, the recently formulated computational model of the basal ganglia combines the main features of the classical direct/indirect pathways and modern reinforcement learning models. The basal ganglia critics (neuromodulators, including the dopaminergic, cholinergic, serotonergic, and histaminergic projections to the striatum) modulate both the excitability of striatal neurons and the efficacy of the cortico-striatal synapses. The model further suggests that the basal ganglia networks are the default connection between the brain structures encoding state and actions.

Degeneration or abnormal activity of basal ganglia neuromodulators leads to abnormal activity of neurons in the main axis of the basal ganglia. Since the basal ganglia networks are the default connection between state and actions, the other neural networks (e.g., cortico-cortical networks) cannot compensate for the abnormal basal ganglia activity. Therapy of basal ganglia-related neurological and psychiatric disorders can be therefore achieved by inactivation of the basal ganglia main axis. Functional inactivation (information lesion) of the basal ganglia networks is achieved by lesion or DBS paradigms and enables compensation by other neuronal networks and restoration of normal behavioral policy.


Parkinson’s disease Dopamine Deep brain stimulation Physiology Computational models Oscillations Synchronization 



This work was supported by the Simone and Bernard Guttman chair of Brain Research, and by the Rosetrees and Vorst foundations (to HB).


  1. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–75.CrossRefGoogle Scholar
  2. Bar-Gad I, Morris G, Bergman H. Information processing, dimensionality reduction and reinforcement learning in the basal ganglia. Prog Neurobiol. 2003;71:439–73.CrossRefGoogle Scholar
  3. Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science. 1990;249:1436–8.CrossRefGoogle Scholar
  4. Bergman H, Wichmann T, Karmon B, DeLong MR. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol. 1994;72:507–20.CrossRefGoogle Scholar
  5. Deffains M, Iskhakova L, Katabi S, Israel Z, Bergman H. Subthalamic, not striatal, activity correlates to basal ganglia downstream activity in normal and parkinsonian monkeys. Elife. 2016;5. pii: e16443.
  6. Filion M, Tremblay L. Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res. 1991;547:142–51.PubMedGoogle Scholar
  7. Filion M, Tremblay L, Bedard PJ. Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res. 1991;547:152–61.PubMedGoogle Scholar
  8. Heimer G, Rivlin-Etzion M, Bar-Gad I, Goldberg JA, Haber SN, Bergman H. Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of parkinsonism. J Neurosci. 2006;26:8101–14.CrossRefGoogle Scholar
  9. Hutchinson WD, Levy R, Dostrovsky JO, Lozano AM, Lang AE. Effects of apomorphine on globus pallidus neurons in parkinsonian patients. Ann Neurol. 1997;42:767–75.CrossRefGoogle Scholar
  10. Lee JI, Verhagen ML, Ohara S, Dougherty PM, Kim JH, Lenz FA. Internal pallidal neuronal activity during mild drug-related dyskinesias in Parkinson’s disease: decreased firing rates and altered firing patterns. J Neurophysiol. 2007;97:2627–41.CrossRefGoogle Scholar
  11. Levy R, Hutchison WD, Lozano AM, Dostrovsky JO. Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity. J Neurosci. 2002a;22:2855–61.CrossRefGoogle Scholar
  12. Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO. Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s disease. Brain. 2002b;125:1196–209.CrossRefGoogle Scholar
  13. Merello M, Balej J, Delfino M, Cammarota A, Betti O, Leiguarda R. Apomorphine induces changes in GPi spontaneous outflow in patients with Parkinson’s disease. Mov Disord. 1999;14:45–9.CrossRefGoogle Scholar
  14. Miller WC, DeLong MR. Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A, editors. The basal ganglia II. New York: Plenum Press; 1987. p. 415–27.Google Scholar
  15. Papa SM, DeSimone R, Fiorani M, Oldfield EH. Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias. Ann Neurol. 1999;46:732–8.CrossRefGoogle Scholar
  16. Parush N, Tishby N, Bergman H. Dopaminergic balance between reward maximization and policy complexity. Front Syst Neurosci. 2011;5:22.CrossRefGoogle Scholar
  17. Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z, Vaadia E, Bergman H. Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron. 2011;72:370–84.CrossRefGoogle Scholar
  18. Schultz W. Reward signaling by dopamine neurons. Neuroscientist. 2001;7:293–302.CrossRefGoogle Scholar
  19. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997;275:1593–9.CrossRefGoogle Scholar
  20. Tobler PN, Fiorillo CD, Schultz W. Adaptive coding of reward value by dopamine neurons. Science. 2005;307:1642–5.CrossRefGoogle Scholar
  21. Weinberger M, Hutchison WD, Lozano AM, Hodaie M, Dostrovsky JO. Increased gamma oscillatory activity in the subthalamic nucleus during tremor in Parkinson’s disease patients. J Neurophysiol. 2009;101:789–802.CrossRefGoogle Scholar
  22. Wichmann T, Soares J. Neuronal firing before and after burst discharges in the monkey Basal Ganglia is predictably patterned in the normal state and altered in parkinsonism. J Neurophysiol. 2016;95:2120–33.CrossRefGoogle Scholar
  23. Wichmann T, Bergman H, DeLong MR. The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. J Neurophysiol. 1994;72:521–30.CrossRefGoogle Scholar
  24. Zaidel A, Spivak A, Grieb B, Bergman H, Israel Z. Subthalamic span of beta oscillations predicts deep brain stimulation efficacy for patients with Parkinson’s disease. Brain. 2010;133:2007–21.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of NeurosurgeryHatay Mustafa Kemal University-Tayfur Ata Sökmen Faculty of MedicineHatayTurkey
  2. 2.Department of Medical Neurobiology (Physiology), Institute of Medical Research—Israel-Canada (IMRIC)The Hebrew University-Hadassah Medical SchoolJerusalemIsrael
  3. 3.Department of NeurosurgeryMaastricht University Medical CenterMaastrichtThe Netherlands
  4. 4.Maastricht University-MHeNS School for Mental Health and NeuroscienceMaastrichtThe Netherlands
  5. 5.The Edmond and Lily Safra Center for Brain Research (ELSC)The Hebrew UniversityJerusalemIsrael

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