Abstract
Considered for a long time a simple relay structure on the so-called indirect pathway of the motor loop within the basal ganglia, the subthalamic nucleus is now considered a critical node in the reward circuitry. This chapter discusses recent evidence for this role in both the animal and clinical literature. There is converging recent evidence to suggest that inactivating this structure could represent an interesting strategy for the treatment of certain forms of reward-related dysfunctions, including drug addiction.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Absher HR, Vogt BA, Clark DG et al (2000) Hypersexuality and hemiballism due to subthalamic infarction. Neuropsychiatry Neuropsychol Behav Neurol 13(3):220–229
Afsharpour S (1985a) Light microscopic analysis of Golgi-impregnated rat subthalamic neurons. J Comp Neurol 236(1):1–13
Afsharpour S (1985b) Topographical projections of the cerebral cortex to the subthalamic nucleus. J Comp Neurol 236(1):14–28
Agid Y, Arnulf I, Bejjani P, Bloch F, Bonnet AM, Damier P, Dubois B, François C, Houeto JL, Iacono D, Karachi C, Mesnage V, Messouak O, Vidailhet M, Welter ML, Yelnik J (2003) Parkinson’s disease is a neuropsychiatric disorder. Adv Neurol 91:365–370
Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282(5387):298–300
Akakin A, Yilmaz BY, Urgun K et al (2014) Hypersexuality after bilateral deep brain stimulation of the subthalamic nucleus for Parkinson’s disease. Neurol India 62:233–234
Amiez C, Joseph JP, Procyk E (2005) Anterior cingulate error-related activity is modulated by predicted reward. Eur J Neurosci 21(12):3447–3452
Bannier S, Montaurier C, Derost PP et al (2009) Overweight after deep brain stimulation of the subthalamic nucleus in Parkinson disease: long term follow-up. J Neurol Neurosurg Psychiatry 80:484–488
Baracz SJ, Cornish JL (2013) Oxytocin modulates dopamine-mediated reward in the rat subthalamic nucleus. Horm Behav 63:370–375
Baracz SJ, Rourke PI, Pardey MC et al (2012) Oxytocin directly administered into the nucleus accumbens core or subthalamic nucleus attenuates methamphetamine-induced conditioned place preference. Behav Brain Res 228:185–193
Barichella M, Marczewska AM, Mariani C et al (2003) Body weight gain rate in patients with Parkinson’s Disease and deep brain stimulation. Mov Disord 18:1337–1340
Barutca S, Turgut M, Meydan N, Ozsunar Y (2003) Subthalamic nucleus tumor causing hyperphagia—case report. Neurol Med Chir (Tokyo) 43(9):457–460
Baunez C, Robbins TW (1997) Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats. Eur J Neurosci 9(10):2086–2099
Baunez C, Amalric M, Robbins TW (2002) Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus. J Neurosci 22:562–568
Baunez C, Dias C, Cador M, Amalric M (2005) The subthalamic nucleus exerts opposite control on cocaine and ‘natural’ rewards. Nat Neurosci 8:484–489
Benazzouz A, Gross C, Feger J et al (1993) Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 5:382–389
Benazzouz A, Boraud T, Féger J et al (1996) Alleviation of experimental hemiparkinsonism by high-frequency stimulation of the subthalamic nucleus in primates: a comparison with L-Dopa treatment. Mov Disord 11(6):627–632
Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436–1438
Beurrier C, Bezard E, Bioulac B, Gross C (1997) Subthalamic stimulation elicits hemiballismus in normal monkey. Neuroreport 8(7):1625–1629
Bevan MD, Francis CM, Bolam JP (1995) The glutamate-enriched cortical and thalamic input to neurons in the subthalamic nucleus of the rat: convergence with GABA-positive terminals. J Comp Neurol 361(3):491–511
Bezzina G, Boon FS, Hampson CL et al (2008) Effect of quinolinic acid-induced lesions of the subthalamic nucleus on performance on a progressive-ratio schedule of reinforcement: a quantitative analysis. Behav Brain Res 195(2):223–230
Bowman EM, Brown VJ (1998) Effects of excitotoxic lesions of the rat ventral striatum on the perception of reward cost. Exp Brain Res 123(4):439–448
Breysse E, Pelloux Y, Baunez C (2015) The good and bad differentially encoded within the subthalamic nucleus in rats. eNeuro 15:2(5)
Carson DS, Hunt GE, Guastella AJ et al (2010) Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus. Addict Biol 15:448–463
Chabardes S, Polosan M, Krack P et al (2013) Deep brain stimulation for obsessive-compulsive disorder: subthalamic nucleus target. World Neurosurg 80(3-4):S31.e31–8. doi:10.1016/j.wneu.2012.03.010
Coizet V, Graham JH, Moss J et al (2009) Short-latency visual input to the subthalamic nucleus is provided by the midbrain superior colliculus. J Neurosci 29(17):5701–5709
Darbaky Y, Baunez C, Arecchi P et al (2005) Reward related neuronal activity in the subthalamic nucleus of the monkey. Neuroreport 16(11):1241–1244
Degos B, Deniau JM, Le Cam J et al (2008) Evidence for a direct subthalamo-cortical loop circuit in the rat. Eur J Neurosci 27(10):2599–2610
Dudek M, Abo-Ramadan U, Hermann D, Brown M, Canals S, Sommer WH, Hyytia P (2015) Brain activation induced by voluntary alcohol and saccharin drinking in rats assessed with manganese-enhanced magnetic resonance imaging. Addict Biol 20(6):1012–1021. doi:10.1111/adb.12179
Espinosa-Parrilla JF, Baunez C, Apicella P (2015) Modulation of neuronal activity by reward identity in the monkey subthalamic nucleus. Eur J Neurosci 42(1):1705–1717
Eusebio A, Witjas T, Cohen J, Fluchère F, Jouve E, Régis J, Azulay JP (2013) Subthalamic nucleus stimulation and compulsive use of dopaminergic medication in Parkinson’s disease. J Neurol Neurosurg Psychiatry 84(8):868–874
Groenewegen HJ, Berendse HW (1990) Connections of the subthalamic nucleus with ventral striatopallidal parts of the basal ganglia in the rat. J Comp Neurol 294(4):607–622
Groenewegen HJ, Berendse HW, Wolters JG, Lohman AH (1990) The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. Prog Brain Res 85:95–116
Gubellini P, Salin P, Kerkerian-Le Goff L, Baunez C (2009) Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior. Prog Neurobiol 89(1):79–123
Hachem-Delaunay S, Fournier ML, Cohen C, Bonneau N, Cador M, Baunez C, Le Moine C (2015) Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit. Neurobiol Dis 80:54–62
Hamani C, Saint-Cyr JA, Fraser J, Kaplitt M, Lozano AM (2004) The subthalamic nucleus in the context of movement disorders. Brain 127(1):4–20
Hammond C, Yelnik J (1983) Intracellular labelling of rat subthalamic neurones with horseradish peroxidase: computer analysis of dendrites and characterization of axon arborization. Neuroscience 8(4):781–790
Hammond C, Rouzaire-Dubois B, Feger J et al (1983) Anatomical and electrophysiological studies on the reciprocal projections between the subthalamic nucleus and nucleus tegmenti pedunculopontinus in the rat. Neuroscience 9(1):41–52
Haynes WI, Haber SN (2013) The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for Basal Ganglia models and deep brain stimulation. J Neurosci 33(11):4804–4814
Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134(3483):943–944
Inase M, Tokuno H, Nambu A et al (1999) Corticostriatal and corticosubthalamic input zones from the presupplementary motor area in the macaque monkey: comparison with the input zones from the supplementary motor area. Brain Res 833(2):191–201
Jackson A, Crossman AR (1981) Subthalamic nucleus efferent projection to the cerebral cortex. Neuroscience 6(11):2367–2377
Joel D, Weiner I (1997) The connections of the primate subthalamic nucleus: indirect pathways and the open interconnected scheme of basal ganglia thalamocortical circuitry. Brain Res Rev 23(1-2):62–78
Kantak KM, Yager LM, Brisotti MF (2013) Impact of medial orbital cortex and medial subthalamic nucleus inactivation, individually and together, on the maintenance of cocaine self-administration behavior in rats. Behav Brain Res 238:1–9
Kita H, Kitai ST (1987) Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J Comp Neurol 260(3):435–452
Kita T, Osten P, Kita H (2014) Rat subthalamic nucleus and zona incerta share extensively overlapped representations of cortical functional territories. J Comp Neurol 522(18):4043–4056
Kitai ST, Deniau JM (1981) Cortical inputs to the subthalamus: intracellular analysis. Brain Res 214(2):411–415
Knobel D, Aybek S, Pollo C et al (2008) Rapid resolution of dopamine dysregulation syndrome (DDS) after subthalamic DBS for Parkinson disease (PD): a case report. Cogn Behav Neurol 21:187–189
Künzle H, Akert K (1977) Efferent connections of cortical, area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. J Comp Neurol 173(1):147–164
Lardeux S, Baunez C (2008) Alcohol preference influences the subthalamic nucleus control on motivation for alcohol in rats. Neuropsychopharmacology 33:634–642
Lardeux S, Pernaud R, Paleressompoulle D, Baunez C (2009) Beyond the reward pathway: coding reward magnitude and error in the rat subthalamic nucleus. J Neurophysiol 102:2526–2537
Lardeux S, Paleressompoulle D, Pernaud R et al (2013) Different populations of subthalamic neurons encode cocaine versus sucrose reward and predict future error. J Neurophysiol 110(7):1497–1510
Lawrence AD, Evans AH, Lees AJ (2003) Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry? Lancet Neurol 2(10):595–604
Le Jeune F, Drapier D, Bourguignon A et al (2009) Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study. Neurology 73(21):1746–1751
Levesque J, Parent A (2005) GABAergic interneurons in human subthalamic nucleus. Mov Disord 20(5):574–584
Lhommee E, Klinger H, Thobois S et al (2012) Subthalamic stimulation in Parkinson’s disease: restoring the balance of motivated behaviours. Brain 135:1463–1477
Lim SY, O’Sullivan SS, Kotschet K et al (2009) Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson’s disease. J Clin Neurosci 16:1148–1152
Limousin P, Pollak P, Benazzouz A, Hoffmann D et al (1995) Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345:91–95
Macia F, Perlemoine C, Coman I, Guehl D, Burbaud P, Cuny E et al (2004) Parkinson’s disease patients with bilateral subthalamic deep brain stimulation gain weight. Mov Disord 19:206–212
Mallet L, Polosan M, Jaafari N et al (2008) Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 359:2121–2134
Martinez-Fernandez R, Pelissier P, Quesada JL et al (2016) Postoperative apathy can neutralise benefits in quality of life after subthalamic stimulation for Parkinson’s disease. J Neurol Neurosurg Psychiatry 87(3):311–318. doi:10.1136/jnnp-2014-310189
Matsumura M, Kojima J, Gardiner TW, Hikosaka O (1992) Visual and oculomotor functions of monkey subthalamic nucleus. J Neurophysiol 67(6):1615–1632
Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14(2-3):69–97
Monakow KH, Akert K, Kunzle H (1978) Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey. Exp Brain Res 33(3-4):395–403
Montaurier C, Morio B, Bannier S et al (2007) Mechanisms of body weight gain in patients with Parkinson’s disease after subthalamic stimulation. Brain 130:1808–1818
Morris LS, Kundu P, Baek K et al (2015) Jumping the gun: mapping neural correlates of waiting impulsivity and relevance across alcohol misuse. Biol Psychiatry 79(6):499–507
Nambu A, Takada M, Inase M, Tokuno H (1996) Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area. J Neurosci 16(8):2671–2683
Nauta HJ, Cole M (1978) Efferent projections of the subthalamic nucleus: an autoradiographic study in monkey and cat. J Comp Neurol 180(1):1–16
Novakova L, Ruzicka E, Jech R, Serranova T, Dusek P, Urgosik D (2007) Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Neuroendocrinol Lett 28:21–25
Novakova L, Haluzik M, Jech R et al (2011) Hormonal regulators of food intake and weight gain in Parkinson’s disease after subthalamic nucleus stimulation. Neuro Endocrinol Lett 32(4):437–441
Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry. Brain Res Rev 20(1):128–154
Pelloux Y, Baunez C (2013) Deep brain stimulation for addiction: why the subthalamic nucleus should be favored. Curr Opin Neurobiol 23(4):713–720
Pelloux Y, Meffre J, Giorla E, Baunez C (2014) The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation. Front Behav Neurosci 8:414
Pelloux Y, Degoulet M, Tiran-Cappello A, Cohen C, Lardeux S, George O, Koob GF, Ahmed SH and Baunez C, Turning off the subthalamic nucleus prevents escalation of cocaine intake and restores controlled use after escalation. In preparation.
Pollak P, Benabid AL, Gervason CL et al (1993) Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor. Adv Neurol 60:408–413
Pratt WE, Choi E, Guy EG (2012) An examination of the effects of subthalamic nucleus inhibition or μ-opioid receptor stimulation on food-directed motivation in the non-deprived rat. Behav Brain Res 230(2):365–373
Ricardo JA (1980) Efferent connections of the subthalamic region in the rat in the subthalamic nucleus of Luys. Brain Res 202(2):257–271
Rieu I, Derost P, Ulla M et al (2011) Body weight gain and deep brain stimulation. J Neurol Sci 310(1-2):267–270
Rouaud T, Lardeux S, Panayotis N et al (2010) Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation. Proc Natl Acad Sci U S A 107:1196–1200
Růžička F, Jech R, Nováková L et al (2012) Weight gain is associated with medial contact site of subthalamic stimulation in Parkinson’s disease. PLoS One 7(5):e38020
Sauleau P, Eusebio A, Vandenberghe W et al (2009) Deep brain stimulation modulates effects of motivation in Parkinson’s disease. Neuroreport 20(6):622–626
Serranová T, Sieger T, Dušek P et al (2013) Sex, food and threat: startling changes after subthalamic stimulation in Parkinson’s disease. Brain Stimul 6(5):740–745
Smith Y, Hazrati LN, Parent A (1990) Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method. J Comp Neurol 294(2):306–323
Strowd RE, Cartwright MS, Passmore LV et al (2010) Weight change following deep brain stimulation for movement disorders. J Neurol 257:1293–1297
Takada M, Tokuno H, Hamada M et al (2001) Organization of inputs from cingulate motor areas to basal ganglia in macaque monkey. Eur J Neurosci 14(10):1633–1650
Teagarden MA, Rebec GV (2007) Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task. J Neurophysiol 97(3):2042–2058
Tremblay L, Schultz W (1999) Relative reward preference in primate orbitofrontal cortex. Nature 398(6729):704–708
Trillet M, Vighetto A, Croisile B et al (1995) Hemiballismus with logorrhea and thymo-affective disinhibition caused by hematoma of the left subthalamic nucleus. Rev Neurol (Paris) 151(6-7):416–419
Tuite PJ, Maxwell RE, Ikramuddin S et al (2005) Weight and body mass index in Parkinson’s disease patients after deep brain stimulation surgery. Parkinsonism Relat Disord 11:247–252
Uslaner JM, Yang P, Robinson TE (2005) Subthalamic nucleus lesions enhance the psychomotor-activating, incentive motivational, and neurobiological effects of cocaine. J Neurosci 25(37):8407–8415
Uslaner JM, Dell Orco JM, Pevzner A, Robinson TE (2008) The influence of subthalamic nucleus lesions on sign-tracking to stimuli paired with food and drug rewards: facilitation of incentive salience attribution? Neuropsychopharmacology 33:2352–2361
Vaccari C, Lolait SJ, Ostrowski NL (1998) Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 139(12):5015–5033
Van Der Kooy D, Hattori T (1980) Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat. J Comp Neurol 192(4):751–768
Visser-Vandewalle V, Van der Linden C, Temel Y et al (2005) Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study. Parkinsonism Relat Disord 11:157–165
Wade CL, Hernandez DO, Breysse E et al (Submitted) Preclinical evidence for therapeutic efficacy of high-frequency stimulation of the subthalamic nucleus for heroin dependence
Winstanley CA, Baunez C, Theobald DE, Robbins TW (2005) Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control. Eur J Neurosci 21(11):3107–3116
Witjas T, Baunez C, Henry JM et al (2005) Addiction in Parkinson’s disease: impact of subthalamic nucleus deep brain stimulation. Mov Disord 20:1052–1055
Wolf ME (2002) Addiction: making the connection between behavioral changes and neuronal plasticity in specific pathways. Mol Interv 2(3):146–157
Zenon A, Duclos Y, Carron R et al (2016) The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making. Brain 139(Pt 6):1830–1843
Zijlstra F, Veltman DJ, Booij J, van den Brink W, Franken IH (2009) Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug Alcohol Depend 99(1-3):183–192
Acknowledgment
The author’s work reported in this chapter has been supported by grants from the Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université, the Agence Nationale pour la Recherche (ANR-09-MNPS-028-01 and ANR 2010-NEUR-005-01 in the framework of the ERA-Net NEURON and projet “investissement d’avenir” A*MIDEX with reference ANR-11-IDEX-0001-02), the IREB (Institut de Recherches Scientifiques sur les Boissons), and Fondation pour le Recherche Médicale (FRM, DPA20140629789).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Baunez, C. (2016). The Subthalamic Nucleus and Reward-Related Processes. In: Soghomonian, JJ. (eds) The Basal Ganglia. Innovations in Cognitive Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-42743-0_14
Download citation
DOI: https://doi.org/10.1007/978-3-319-42743-0_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-42741-6
Online ISBN: 978-3-319-42743-0
eBook Packages: Behavioral Science and PsychologyBehavioral Science and Psychology (R0)