Abstract
Associative learning requires the ability to learn the connections between events. Fundamental to the learning process is acquiring the expectation that certain events lead to certain outcomes. Indeed, studies have shown that when an expected outcome is changed, so does the subsequent behavior. It has also been demonstrated that basal ganglia neuronal activity is highly modulated by the expectation of future reward. However, the direct link between reward expectation, basal ganglia neuronal activity, and the final change in behavior is not clear. Electrical stimulation enables a direct manipulation of neuronal activity and has been shown to cause behavioral changes. From another perspective, high-frequency deep brain electrical stimulation (DBS) is used as treatment of advanced neurological disorders, yet the underlying mechanism is still a topic of debate.
We investigated the effect of high-frequency stimulation of the external segment of the globus pallidus, the central nucleus of the basal ganglia networks, on monkey’s expectations of both reward and aversive events. We show that long-duration (30 min), high-frequency (130 Hz) stimulation changed the monkey’s behavior in a classical conditioning task, enhancing its expectation of reward. The effect we observed was gradual and persisted even after stimulation had ceased, implying a plastic change. The results support the notion of asymmetric coding of the positive vs. negative domains in the basal ganglia and may suggest the GPe as another possible target for DBS therapy of depression.
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Arkadir D, Morris G, Vaadia E and Bergman H (2004) Independent coding of movement direction and reward prediction by single pallidal neurons. J Neurosci 24: 10047–10056.
Benabid AL, Benazzouz A, Hoffmann D, Limousin P, Krack P and Pollak P (1998) Long-term electrical inhibition of deep brain targets in movement disorders. Mov Disord 13(Suppl 3): 119–125.
Berardelli A, Rothwell JC, Hallett M, Thompson PD, Manfredi M and Marsden CD (1998) The pathophysiology of primary dystonia. Brain 121: 1195–1212.
Bevan MD, Smith AD and Bolam JP (1996) The substantia nigra as a site of synaptic integration of functionally diverse information arising from the ventral pallidum and the globus pallidus in the rat. Neuroscience 75: 5–12.
Bittar RG, Yianni J, Wang S, Liu X, Nandi D, Joint C, Scott R, Bain PG, Gregory R, Stein J and Aziz TZ (2005) Deep brain stimulation for generalised dystonia and spasmodic torticollis. J Clin Neurosci 12: 12–16.
Brecht M, Schneider M, Sakmann B and Margrie TW (2004) Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex. Nature 427: 704–710.
Darbaky Y, Baunez C, Arecchi P, Legallet E and Apicella P (2005) Reward-related neuronal activity in the subthalamic nucleus of the monkey. Neuroreport 16: 1241–1244.
Ding L and Hikosaka O (2007) Temporal development of asymmetric reward-induced bias in macaques. J Neurophysiol 97: 57–61.
Frank MJ, Samanta J, Moustafa AA and Sherman SJ (2007) Hold your horses: Impulsivity, deep brain stimulation, and medication in parkinsonism. Science 318: 1309–1312.
Hollerman JR and Schultz W (1998) Dopamine neurons report an error in the temporal prediction of reward during learning. Nat Neurosci 1: 304–309.
Huber D, Petreanu L, Ghitani N, Ranade S, Hromadka T, Mainen Z and Svoboda K (2008) Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451: 61–64.
Johansen-Berg H, Gutman DA, Behrens TE, Matthews PM, Rushworth MF, Katz E, Lozano AM and Mayberg HS (2008) Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex 18: 1374–1383.
Joshua M, Adler A, Mitelman R, Vaadia E, Bergman H. (2008) Midbrain dopaminergic neurons and striatal cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J Neurosci 28: 11673–11684.
Kelly PH, Seviour PW and Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94: 507–522.
Konorski J (1967) Integrative Activity of the Brain: An Interdiciplinary Approach. Chicago, IL: Chicago University Press.
Kosel M, Sturm V, Frick C, Lenartz D, Zeidler G, Brodesser D and Schlaepfer TE (2007) Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. J Psychiatr Res 41: 801–803.
Lauwereyns J, Watanabe K, Coe B and Hikosaka O (2002) A neural correlate of response bias in monkey caudate nucleus. Nature 418: 413–417.
Macmillan NA and Creelman CD (2005) Detection Theory. Mahwah, NJ: Lawrence Erlbaum Associates.
Martin RF and Bowden DM (1996) A stereotaxic template atlas of the macaque brain for digital imaging and quantitative neuroanatomy. Neuroimage 4: 119–150.
Milstein DM and Dorris MC (2007) The influence of expected value on saccadic preparation. J Neurosci 27: 4810–4818.
Nakamura K and Hikosaka O (2006) Facilitation of saccadic eye movements by postsaccadic electrical stimulation in the primate caudate. J Neurosci 26: 12885–12895.
Olds J and Milner P (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol 47: 419–427.
Paladini CA, Celada P and Tepper JM (1999) Striatal, pallidal, and pars reticulata evoked inhibition of nigrostriatal dopaminergic neurons is mediated by GABA(A) receptors in vivo. Neuroscience 89: 799–812.
Perlmutter JS and Mink JW (2006) Deep brain stimulation. Annu Rev Neurosci 29: 229–257.
Redgrave P and Dean P (1981) Intracranial self-stimulation. Br Med Bull 37: 141–146.
Reynolds JN and Wickens JR (2002) Dopamine-dependent plasticity of corticostriatal synapses. Neural Netw 15: 507–521.
Salzman CD, Britten KH and Newsome WT (1990) Cortical microstimulation influences perceptual judgements of motion direction. Nature 346: 174–177.
Samejima K, Ueda Y, Doya K and Kimura M (2005) Representation of action-specific reward values in the striatum. Science 310: 1337–1340.
Sato M and Hikosaka O (2002) Role of primate substantia nigra pars reticulata in reward-oriented saccadic eye movement. J Neurosci 22: 2363–2373.
Strunk DR, Lopez H and DeRubeis RJ (2006) Depressive symptoms are associated with unrealistic negative predictions of future life events. Behav Res Ther 44: 861–882.
Tisch S, Rothwell JC, Bhatia KP, Quinn N, Zrinzo L, Jahanshahi M, Ashkan K, Hariz M and Limousin P (2007) Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalised dystonia. Exp Neurol 206: 80–85.
Watanabe M, Cromwell HC, Tremblay L, Hollerman JR, Hikosaka K and Schultz W (2001) Behavioral reactions reflecting differential reward expectations in monkeys. Exp Brain Res 140: 511–518.
Williams ZM and Eskandar EN (2006) Selective enhancement of associative learning by microstimulation of the anterior caudate. Nat Neurosci 9: 562–568.
Yianni J, Bain PG, Gregory RP, Nandi D, Joint C, Scott RB, Stein JF and Aziz TZ (2003) Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation. Eur J Neurol 10: 239–247.
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Adler, A., Joshua, M., Finkes, I., Bergman, H. (2009). High-Frequency Stimulation of the Globus Pallidus External Segment Biases Behavior Toward Reward. In: Groenewegen, H., Voorn, P., Berendse, H., Mulder, A., Cools, A. (eds) The Basal Ganglia IX. Advances in Behavioral Biology, vol 58. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0340-2_7
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DOI: https://doi.org/10.1007/978-1-4419-0340-2_7
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