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The Basal Ganglia pp 363–388Cite as

Motivational Deficits in Parkinson’s Disease: Role of the Dopaminergic System and Deep-Brain Stimulation of the Subthalamic Nucleus

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Part of the book series: Innovations in Cognitive Neuroscience ((Innovations Cogn.Neuroscience))

Abstract

Beyond motor symptoms, Parkinson’s disease (PD) patients also exhibit a cluster of neuropsychiatric symptoms, which are now recognized as major contributors to morbidity, severely impairing the patient’s quality of life. Among them, apathy, with a frequency that varies from 16.5 to 70 % depending on the assessment scale used and the population studied, appears to be a major neuropsychiatric feature of PD. In addition, apathy is viewed as a major postoperative complication of deep brain stimulation of the subthalamic nucleus (STN-DBS). Despite this prevalence, the pathogenesis of apathy in PD remains elusive. Importantly, levodopa and dopaminergic agonists, such as the D2/D3 receptor agonist ropinirole, greatly attenuate apathy in Parkinsonian patient, suggesting an important role of dopamine in its pathophysiology. Nevertheless, it is difficult to disentangle the specific role of the dopaminergic denervation and that of DBS in the development of apathy since it has been reported that STN-DBS influences dopaminergic function on its own. Approaches relying on experimental models of PD and STN-DBS thereby can be useful tools to dissect the potential causal contribution of these two factors and their possible interactions. In this chapter, we present recent experimental and clinical data, which provides a better understanding of the role of the dopaminergic system and STN-DBS in the motivational deficits observed in PD. In light of this literature, apathy can be considered as a plurifactorial motivational deficit with a critical role of dopamine acting synergistically with the DBS of STN regions associated with the nigrostriatal and the mesolimbic system.

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Notes

  1. 1.

    The term “goal-directed behavior ” can be misleading and should be viewed as a “behavior directed toward a goal” and not as a “behavior directed by a goal”, as the second has a strong theoretical connotation referring to a specific psychobiological process and putative functional sub-compartmentalization of the dorsal striatum (Belin et al. 2009; Yin and Knowlton 2006).

References

  • Aarsland D, Bronnick K, Alves G et al (2009a) The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson’s disease. J Neurol Neurosurg Psychiatry 80(8):928–930

    Article  PubMed  Google Scholar 

  • Aarsland D, Marsh L, Schrag A (2009b) Neuropsychiatric symptoms in Parkinson’s disease. Mov Disord 24(15):2175–2186. doi:10.1002/mds.22589

    Article  PubMed  PubMed Central  Google Scholar 

  • Abosch A, Kapur S, Lang AE et al (2003) Stimulation of the subthalamic nucleus in Parkinson’s disease does not produce striatal dopamine release. Neurosurgery 53(5):1095–1102, discussion 1102-1095

    Article  PubMed  Google Scholar 

  • Agid Y, Ruberg M, Dubois B, Javoy-Agid F (1984) Biochemical substrates of mental disturbances in Parkinson’s disease. Adv Neurol 40:211–218

    PubMed  Google Scholar 

  • Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381. doi:10.1146/annurev.ne.09.030186.002041

    Article  PubMed  Google Scholar 

  • APA (1994) Diagnostic and statistical manual of mental disorders—DSM IV, 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  • APA (2013) Diagnostic and statistical manual of mental disorders—DSM 5, 5th edn. American Psychiatric, Washington, DC

    Google Scholar 

  • Ballanger B, Klinger H, Eche J et al (2012) Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson’s disease. Mov Disord 27(1):84–89. doi:10.1002/mds.23895

    Article  PubMed  Google Scholar 

  • Baunez C, Lardeux S (2011) Frontal cortex-like functions of the subthalamic nucleus. Front Syst Neurosci 5:83. doi:10.3389/fnsys.2011.00083

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Baunez C, Dias C, Cador M et al (2005) The subthalamic nucleus exerts opposite control on cocaine and ‘natural’ rewards. Nat Neurosci 8(4):484–489

    PubMed  Google Scholar 

  • Baunez C, Christakou A, Chudasama Y et al (2007) Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats. Eur J Neurosci 25(4):1187–1194

    Article  PubMed  PubMed Central  Google Scholar 

  • Baunez C, Yelnik J, Mallet L (2011) Six questions on the subthalamic nucleus: lessons from animal models and from stimulated patients. Neuroscience 198:193–204. doi:10.1016/j.neuroscience.2011.09.059, pii:S0306-4522(11)01145-6

    Article  PubMed  Google Scholar 

  • Bejjani BP, Dormont D, Pidoux B et al (2000) Bilateral subthalamic stimulation for Parkinson’s disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance. J Neurosurg 92(4):615–625. doi:10.3171/jns.2000.92.4.0615

    Article  PubMed  Google Scholar 

  • Belin D, Jonkman S, Dickinson A et al (2009) Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction. Behav Brain Res 199(1):89–102

    Article  PubMed  Google Scholar 

  • Belin D, Belin-Rauscent A, Murray JE et al (2013) Addiction: failure of control over maladaptive incentive habits. Curr Opin Neurobiol 23(4):564–572

    Article  PubMed  Google Scholar 

  • Benabid AL, Benazzouz A, Hoffmann D et al (1998) Long-term electrical inhibition of deep brain targets in movement disorders. Mov Disord 13(Suppl 3):119–125

    PubMed  Google Scholar 

  • Benabid AL, Krack PP, Benazzouz A et al (2000) Deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: methodologic aspects and clinical criteria. Neurology 55(12 Suppl 6):S40–S44

    PubMed  Google Scholar 

  • 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(4):382–389

    Article  PubMed  Google Scholar 

  • Beninger RJ, Ranaldi R (1993) Microinjections of flupenthixol into the caudate-putamen but not the nucleus accumbens, amygdala or frontal cortex of rats produce intra-session declines in food-rewarded operant responding. Behav Brain Res 55(2):203–212

    Article  PubMed  Google Scholar 

  • Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology (Berl) 191(3):391–431. doi:10.1007/s00213-006-0578-x

    Article  Google Scholar 

  • Beurrier C, Bioulac B, Audin J et al (2001) High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85(4):1351–1356

    PubMed  Google Scholar 

  • Bonito-Oliva A, Masini D, Fisone G (2014) A mouse model of non-motor symptoms in Parkinson’s disease: focus on pharmacological interventions targeting affective dysfunctions. Front Behav Neurosci 8:290. doi:10.3389/fnbeh.2014.00290

    Article  PubMed  PubMed Central  Google Scholar 

  • Branchi I, D’Andrea I, Armida M et al (2008) Nonmotor symptoms in Parkinson’s disease: investigating early-phase onset of behavioral dysfunction in the 6-hydroxydopamine-lesioned rat model. J Neurosci Res 86(9):2050–2061. doi:10.1002/jnr.21642

    Article  PubMed  Google Scholar 

  • Brizard M, Carcenac C, Bemelmans AP et al (2006) Functional reinnervation from remaining DA terminals induced by GDNF lentivirus in a rat model of early Parkinson’s disease. Neurobiol Dis 21(1):90–101

    Article  PubMed  Google Scholar 

  • Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68(5):815–834

    Article  PubMed  PubMed Central  Google Scholar 

  • Brown RG, Pluck G (2000) Negative symptoms: the ‘pathology’ of motivation and goal-directed behaviour. Trends Neurosci 23(9):412–417

    Article  PubMed  Google Scholar 

  • Bruet N, Windels F, Bertrand A et al (2001) High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats. J Neuropathol Exp Neurol 60(1):15–24

    Article  PubMed  Google Scholar 

  • Carcenac C, Favier M, Vachez Y et al (2015) Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats. Mov Disord 30(13):1739–1749. doi:10.1002/mds.26146

    Article  PubMed  Google Scholar 

  • Carnicella S, Drui G, Boulet S et al (2014) Implication of dopamine D3 receptor activation in the reversion of Parkinson’s disease-related motivational deficits. Transl Psychiatry 4:e401

    Article  PubMed  PubMed Central  Google Scholar 

  • Carriere N, Besson P, Dujardin K et al (2010) Apathy in Parkinson’s disease is associated with nucleus accumbens atrophy: a magnetic resonance imaging shape analysis. Mov Disord 29(7):897–903

    Article  Google Scholar 

  • Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5):464–474

    Article  PubMed  Google Scholar 

  • Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5(3):235–245

    Article  PubMed  Google Scholar 

  • Chen L, Deltheil T, Turle-Lorenzo N et al (2014) SK channel blockade reverses cognitive and motor deficits induced by nigrostriatal dopamine lesions in rats. Int J Neuropsychopharmacol 17(8):1295–1306

    Article  PubMed  Google Scholar 

  • Craufurd D, Thompson JC, Snowden JS (2001) Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol 14(4):219–226

    PubMed  Google Scholar 

  • Creed MC, Hamani C, Nobrega JN (2013) Effects of repeated deep brain stimulation on depressive- and anxiety-like behavior in rats: comparing entopeduncular and subthalamic nuclei. Brain Stimul 6(4):506–514

    Article  PubMed  Google Scholar 

  • Czernecki V, Pillon B, Houeto JL et al (2002) Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia 40(13):2257–2267

    Article  PubMed  Google Scholar 

  • Czernecki V, Pillon B, Houeto JL et al (2005) Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson’s disease? J Neurol Neurosurg Psychiatry 76(6):775–779

    Article  PubMed  PubMed Central  Google Scholar 

  • Czernecki V, Schupbach M, Yaici S et al (2008) Apathy following subthalamic stimulation in Parkinson disease: a dopamine responsive symptom. Mov Disord 23(7):964–969. doi:10.1002/mds.21949

    Article  PubMed  Google Scholar 

  • Darbaky Y, Forni C, Amalric M et al (2003) High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task. Eur J Neurosci 18(4):951–956, pii:2803

    Article  PubMed  Google Scholar 

  • 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, pii:00001756-200508010-00022

    Article  PubMed  Google Scholar 

  • David R, Koulibaly M, Benoit M et al (2008) Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases A SPECT study with partial volume effect correction. Clin Neurol Neurosurg 110(1):19–24. pii:S0303-8467(07)00231-4

    Google Scholar 

  • Delaville C, Chetrit J, Abdallah K et al (2012) Emerging dysfunctions consequent to combined monoaminergic depletions in Parkinsonism. Neurobiol Dis 45(2):763–773. pii:S0969-9961(11)00355-X

    Google Scholar 

  • Del-Monte J, Capdevielle D, Gely-Nargeot MC et al (2013) [Evolution of the concept of apathy: the need for a multifactorial approach in schizophrenia]. Encephale 39(Suppl 1):S57–S63. pii:S0013-7006(12)00281-3

    Google Scholar 

  • Denheyer M, Kiss ZH, Haffenden AM (2009) Behavioral effects of subthalamic deep brain stimulation in Parkinson’s disease. Neuropsychologia 47(14):3203–3209. pii:S0028-3932(09)00314-5

    Google Scholar 

  • Deniau JM, Degos B, Bosch C et al (2010) Deep brain stimulation mechanisms: beyond the concept of local functional inhibition. Eur J Neurosci 32(7):1080–1091. doi:10.1111/j.1460-9568.2010.07413.x

    Article  PubMed  Google Scholar 

  • Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 35(1):68–77. pii:S0166-2236(11)00192-5

    Google Scholar 

  • Deroche-Gamonet V, Piat F, Le Moal M et al (2002) Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration. Eur J Neurosci 15(8):1363–1370, pii:1974

    Article  PubMed  Google Scholar 

  • Desbonnet L, Temel Y, Visser-Vandewalle V et al (2004) Premature responding following bilateral stimulation of the rat subthalamic nucleus is amplitude and frequency dependent. Brain Res 1008(2):198–204

    Article  PubMed  Google Scholar 

  • Dostrovsky JO, Levy R, Wu JP et al (2000) Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 84(1):570–574

    PubMed  Google Scholar 

  • Drapier D, Drapier S, Sauleau P et al (2006) Does subthalamic nucleus stimulation induce apathy in Parkinson’s disease? J Neurol 253(8):1083–1091. doi:10.1007/s00415-006-0177-0

    Article  PubMed  Google Scholar 

  • Drijgers RL, Dujardin K, Reijnders JS et al (2012) Validation of diagnostic criteria for apathy in Parkinson’s disease. Parkinsonism Relat Disord 16(10):656–660. pii:S1353-8020(10)00213-0

    Google Scholar 

  • Drui G, Carnicella S, Carcenac C et al (2014) Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson’s disease. Mol Psychiatry 19(3):358–367

    Article  PubMed  Google Scholar 

  • Dujardin K, Defebvre L, Krystkowiak P et al (2001) Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson’s disease. J Neurol 248(7):603–611

    Article  PubMed  Google Scholar 

  • Dujardin K, Sockeel P, Delliaux M et al (2008) The Lille Apathy Rating Scale: validation of a caregiver-based version. Mov Disord 23(6):845–849. doi:10.1002/mds.21968

    Article  PubMed  Google Scholar 

  • Dujardin K, Sockeel P, Delliaux M et al (2009) Apathy may herald cognitive decline and dementia in Parkinson’s disease. Mov Disord 24(16):2391–2397. doi:10.1002/mds.22843

    Article  PubMed  Google Scholar 

  • Eskow Jaunarajs KL, George JA, Bishop C (2012) L-DOPA-induced dysregulation of extrastriatal dopamine and serotonin and affective symptoms in a bilateral rat model of Parkinson’s disease. Neuroscience 218:243–256

    Article  PubMed  Google Scholar 

  • Favier M, Duran T, Carcenac C et al (2014) Pramipexole reverses Parkinson’s disease-related motivational deficits in rats. Mov Disord 29(7):912–920. doi:10.1002/mds.25837

    Article  PubMed  Google Scholar 

  • Fibiger HC, Zis AP, McGeer EG (1973) Feeding and drinking deficits after 6-hydroxydopamine administration in the rat: similarities to the lateral hypothalamic syndrome. Brain Res 55(1):135–148, pii:0006-8993(73)90493-9

    Article  PubMed  Google Scholar 

  • Funkiewiez A, Ardouin C, Caputo E et al (2004) Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75(6):834–839

    Article  PubMed  PubMed Central  Google Scholar 

  • Garcia-Rill E, Hyde J, Kezunovic N et al (2014) The physiology of the pedunculopontine nucleus: implications for deep brain stimulation. J Neural Transm 122(2):225–235. doi:10.1007/s00702-014-1243-x

    Article  PubMed  PubMed Central  Google Scholar 

  • Gervais-Bernard H, Xie-Brustolin J, Mertens P et al (2009) Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease: five year follow-up. J Neurol 256(2):225–233. doi:10.1007/s00415-009-0076-2

    Article  PubMed  Google Scholar 

  • Hartung H, Tan SK, Steinbusch HM et al (2011) High-frequency stimulation of the subthalamic nucleus inhibits the firing of juxtacellular labelled 5-HT-containing neurones. Neuroscience 186:135–145

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Herzog J, Volkmann J, Krack P et al (2003) Two-year follow-up of subthalamic deep brain stimulation in Parkinson’s disease. Mov Disord 18(11):1332–1337. doi:10.1002/mds.10518

    Article  PubMed  Google Scholar 

  • Hilker R, Voges J, Ghaemi M et al (2003) Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans. Mov Disord 18(1):41–48. doi:10.1002/mds.10297

    Article  PubMed  Google Scholar 

  • Hollerman JR, Schultz W (1998) Dopamine neurons report an error in the temporal prediction of reward during learning. Nat Neurosci 1(4):304–309. doi:10.1038/1124

    Article  PubMed  Google Scholar 

  • Hollerman JR, Tremblay L, Schultz W (1998) Influence of reward expectation on behavior-related neuronal activity in primate striatum. J Neurophysiol 80(2):947–963

    PubMed  Google Scholar 

  • Houeto JL, Mesnage V, Mallet L et al (2002) Behavioural disorders, Parkinson’s disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 72(6):701–707

    Article  PubMed  PubMed Central  Google Scholar 

  • Ikemoto S, Glazier BS, Murphy JM et al (1997) Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 17(21):8580–8587

    PubMed  Google Scholar 

  • Ilango A, Kesner AJ, Keller KL et al (2014) Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion. J Neurosci 34(3):817–822

    Article  PubMed  PubMed Central  Google Scholar 

  • Isella V, Melzi P, Grimaldi M et al (2002) Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord 17(2):366–371. doi:10.1002/mds.10041

    Article  PubMed  Google Scholar 

  • Ishizaki J, Mimura M (2011) Dysthymia and apathy: diagnosis and treatment. Depress Res Treat 2011:893905. doi:10.1155/2011/893905

    PubMed  PubMed Central  Google Scholar 

  • Kirik D, Rosenblad C, Bjorklund A (1998) Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol 152(2):259–277

    Article  PubMed  Google Scholar 

  • Kirsch-Darrow L, Zahodne LB, Marsiske M et al (2011) The trajectory of apathy after deep brain stimulation: from pre-surgery to 6 months post-surgery in Parkinson’s disease. Parkinsonism Relat Disord 17(3):182–188

    Article  PubMed  PubMed Central  Google Scholar 

  • Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiologic and clinical implications. N Engl J Med 318(14):876–880. doi:10.1056/NEJM198804073181402

    Article  PubMed  Google Scholar 

  • 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. doi:10.1002/cne.902600309

    Article  PubMed  Google Scholar 

  • Kitai ST, Deniau JM (1981) Cortical inputs to the subthalamus: intracellular analysis. Brain Res 214(2):411–415, pii:0006-8993(81)91204-X

    Article  PubMed  Google Scholar 

  • Klavir O, Flash S, Winter C et al (2009) High frequency stimulation and pharmacological inactivation of the subthalamic nucleus reduces ‘compulsive’ lever-pressing in rats. Exp Neurol 215(1):101–109. pii:S0014-4886(08)00370-1

    Google Scholar 

  • Krack P, Pollak P, Limousin P et al (1998) Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 121(Pt 3):451–457

    Article  PubMed  Google Scholar 

  • Krack P, Kumar R, Ardouin C et al (2001) Mirthful laughter induced by subthalamic nucleus stimulation. Mov Disord 16(5):867–875. doi:10.1002/mds.1174

    Article  PubMed  Google Scholar 

  • Krack P, Batir A, Van Blercom N et al (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 349(20):1925–1934

    Article  PubMed  Google Scholar 

  • Krack P, Hariz MI, Baunez C et al (2010) Deep brain stimulation: from neurology to psychiatry? Trends Neurosci 33(10):474–484. pii:S0166-2236(10)00105-0

    Google Scholar 

  • Krause M, Fogel W, Heck A et al (2001) Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus. J Neurol Neurosurg Psychiatry 70(4):464–470

    Article  PubMed  PubMed Central  Google Scholar 

  • Kringelbach ML, Jenkinson N, Owen SL et al (2007) Translational principles of deep brain stimulation. Nat Rev Neurosci 8(8):623–635

    Article  PubMed  Google Scholar 

  • Kumar R, Lozano AM, Sime E et al (1999) Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation. Neurology 53(3):561–566

    Article  PubMed  Google Scholar 

  • Lacombe E, Carcenac C, Boulet S et al (2007) High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats. Eur J Neurosci 26(6):1670–1680

    Article  PubMed  PubMed Central  Google Scholar 

  • Lardeux S, Baunez C (2008) Alcohol preference influences the subthalamic nucleus control on motivation for alcohol in rats. Neuropsychopharmacology 33(3):634–642

    Article  PubMed  Google Scholar 

  • Lardeux S, Pernaud R, Paleressompoulle D et al (2009) Beyond the reward pathway: coding reward magnitude and error in the rat subthalamic nucleus. J Neurophysiol 102(4):2526–2537

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Le Jeune F, Peron J, Grandjean D et al (2010) Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study. Eur J Nucl Med Mol Imaging 37(8):1512–1520. doi:10.1007/s00259-010-1436-y

    Article  PubMed  Google Scholar 

  • Le Moal M, Simon H (1991) Mesocorticolimbic dopaminergic network: functional and regulatory roles. Physiol Rev 71(1):155–234

    PubMed  Google Scholar 

  • Leblois A, Boraud T, Meissner W et al (2006) Competition between feedback loops underlies normal and pathological dynamics in the basal ganglia. J Neurosci 26(13):3567–3583

    Article  PubMed  Google Scholar 

  • Leentjens AF, Koester J, Fruh B et al (2009) The effect of pramipexole on mood and motivational symptoms in Parkinson’s disease: a meta-analysis of placebo-controlled studies. Clin Ther 31(1):89–98

    Article  PubMed  Google Scholar 

  • Levy R, Dubois B (2006) Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 16(7):916–928

    Article  PubMed  Google Scholar 

  • Lhommee E, Klinger H, Thobois S et al (2012) Subthalamic stimulation in Parkinson’s disease: restoring the balance of motivated behaviours. Brain 135(Pt 5):1463–1477

    Article  PubMed  Google Scholar 

  • Li S, Arbuthnott GW, Jutras MJ et al (2007) Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. J Neurophysiol 98(6):3525–3537

    Article  PubMed  Google Scholar 

  • Limousin P, Pollak P, Benazzouz A et al (1995a) Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord 10(5):672–674. doi:10.1002/mds.870100523

    Article  PubMed  Google Scholar 

  • Limousin P, Pollak P, Benazzouz A et al (1995b) Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345(8942):91–95

    Article  PubMed  Google Scholar 

  • Lindgren HS, Dunnett SB (2012) Cognitive dysfunction and depression in Parkinson’s disease: what can be learned from rodent models? Eur J Neurosci 35(12):1894–1907. doi:10.1111/j.1460-9568.2012.08162.x

    Article  PubMed  Google Scholar 

  • Loas G, Krystkowiak P, Godefroy O (2012) Anhedonia in Parkinson’s disease: an overview. J Neuropsychiatry Clin Neurosci 24(4):444–451

    Article  PubMed  Google Scholar 

  • Mallet L, Schupbach M, N’Diaye K et al (2007) Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc Natl Acad Sci U S A 104(25):10661–10666

    Article  PubMed  PubMed Central  Google Scholar 

  • Marin RS (1990) Differential diagnosis and classification of apathy. Am J Psychiatry 147(1):22–30

    Article  PubMed  Google Scholar 

  • Marin RS, Biedrzycki RC, Firinciogullari S (1991) Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res 38(2):143–162, pii:0165-1781(91)90040-V

    Article  PubMed  Google Scholar 

  • Mathai A, Smith Y (2011) The corticostriatal and corticosubthalamic pathways: two entries, one target. So what? Front Syst Neurosci 5:64. doi:10.3389/fnsys.2011.00064

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsumura M, Kojima J, Gardiner TW, Hikosaka O (1992) Visual and oculomotor functions of monkey subthalamic nucleus. J Neurophysiol 67(6):1615–1632

    PubMed  Google Scholar 

  • McIntyre CC, Hahn PJ (2010) Network perspectives on the mechanisms of deep brain stimulation. Neurobiol Dis 38(3):329–337

    Article  PubMed  Google Scholar 

  • McIntyre CC, Savasta M, Kerkerian-Le Goff L et al (2004) Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol 115(6):1239–1248

    Article  PubMed  Google Scholar 

  • Meissner W, Reum T, Paul G et al (2001) Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats. Neurosci Lett 303(3):165–168, pii:S030439400101758X

    Article  PubMed  Google Scholar 

  • Meissner W, Harnack D, Paul G et al (2002) Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats. Neurosci Lett 328(2):105–108, pii:S0304394002004639

    Article  PubMed  Google Scholar 

  • Meissner W, Harnack D, Reese R et al (2003) High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats. J Neurochem 85(3):601–609, pii:1665

    Article  PubMed  Google Scholar 

  • Montgomery EB, Baker KB (2000) Mechanisms of deep brain stimulation and future technical developments. Neurol Res 22(3):259–266

    Article  PubMed  Google Scholar 

  • Moro E, Scerrati M, Romito LM et al (1999) Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease. Neurology 53(1):85–90

    Article  PubMed  Google Scholar 

  • Nambu A (2004) A new dynamic model of the cortico-basal ganglia loop. Prog Brain Res 143:461–466

    Article  PubMed  Google Scholar 

  • Nieoullon A, Coquerel A (2003) Dopamine: a key regulator to adapt action, emotion, motivation and cognition. Curr Opin Neurol 16(Suppl 2):S3–S9

    Article  PubMed  Google Scholar 

  • Nowend KL, Arizzi M, Carlson BB et al (2001) D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses lever pressing for food but leads to compensatory increases in chow consumption. Pharmacol Biochem Behav 69(3-4):373–382, pii:S0091-3057(01)00524-X

    Article  PubMed  Google Scholar 

  • Nozaki T, Sugiyama K, Yagi S et al (2013) Effect of subthalamic nucleus stimulation during exercise on the mesolimbocortical dopaminergic region in Parkinson’s disease: a positron emission tomography study. J Cereb Blood Flow Metab 33(3):415–421

    Article  PubMed  Google Scholar 

  • Palmiter RD (2008) Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice. Ann N Y Acad Sci 1129:35–46

    Article  PubMed  PubMed Central  Google Scholar 

  • Parent A, Hazrati LN (1995a) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Brain Res Rev 20:91-127.

    Google Scholar 

  • Parent A, Hazrati LN (1995b) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128–154

    Google Scholar 

  • Paul G, Reum T, Meissner W et al (2000) High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat. Neuroreport 11(3):441–444

    Article  PubMed  Google Scholar 

  • Paxinos, G. & Watson, C. The rat brain in stereotaxic coordinates (Elesvier Academic Press, San Diego, 1998)

    Google Scholar 

  • Pazo JH, Hocht C, Barcelo AC et al (2010) Effect of electrical and chemical stimulation of the subthalamic nucleus on the release of striatal dopamine. Synapse 64(12):905–915. doi:10.1002/syn.20809

    Article  PubMed  Google Scholar 

  • Pedersen KF, Alves G, Bronnick K et al (2009) Apathy in drug-naive patients with incident Parkinson’s disease: the Norwegian ParkWest study. J Neurol 257(2):217–223. doi:10.1007/s00415-009-5297-x

    Article  PubMed  Google Scholar 

  • Peron J, Fruhholz S, Verin M et al (2013) Subthalamic nucleus: a key structure for emotional component synchronization in humans. Neurosci Biobehav Rev 37(3):358–373

    Article  PubMed  Google Scholar 

  • Pluck GC, Brown RG (2002) Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73(6):636–642

    Article  PubMed  PubMed Central  Google Scholar 

  • Poewe W (2008) Non-motor symptoms in Parkinson’s disease. Eur J Neurol 15(Suppl 1):14–20

    Article  PubMed  Google Scholar 

  • Politis M, Wu K, Loane C et al (2012) Serotonin neuron loss and nonmotor symptoms continue in Parkinson’s patients treated with dopamine grafts. Sci Transl Med 4(128):128ra141

    Article  Google Scholar 

  • Redgrave P, Rodriguez M, Smith Y et al (2010) Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease. Nat Rev Neurosci 11(11):760–772

    Article  PubMed  PubMed Central  Google Scholar 

  • Reijnders JS, Scholtissen B, Weber WE et al (2010) Neuroanatomical correlates of apathy in Parkinson’s disease: a magnetic resonance imaging study using voxel-based morphometry. Mov Disord 25(14):2318–2325. doi:10.1002/mds.23268

    Article  PubMed  Google Scholar 

  • Remy P, Doder M, Lees A, Turjanski N et al (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128(Pt 6):1314–1322

    Article  PubMed  Google Scholar 

  • Rossi MA, Sukharnikova T, Hayrapetyan VY et al (2013) Operant self-stimulation of dopamine neurons in the substantia nigra. PLoS One 8(6):e65799

    Article  PubMed  PubMed Central  Google Scholar 

  • 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(3):1196–1200

    Article  PubMed  Google Scholar 

  • Saint-Cyr JA, Trepanier LL, Kumar R et al (2000) Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson’s disease. Brain 123(Pt 10):2091–2108

    Article  PubMed  Google Scholar 

  • Salamone JD, Correa M, Mingote S et al (2003) Nucleus accumbens dopamine and the regulation of effort in food-seeking behavior: implications for studies of natural motivation, psychiatry, and drug abuse. J Pharmacol Exp Ther 305(1):1–8. doi:10.1124/jpet.102.035063

    Article  PubMed  Google Scholar 

  • Salamone JD, Correa M, Farrar A et al (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology (Berl) 191(3):461–482. doi:10.1007/s00213-006-0668-9

    Article  Google Scholar 

  • Salamone JD, Correa M, Nunes EJ et al (2012) The behavioral pharmacology of effort-related choice behavior: dopamine, adenosine and beyond. J Exp Anal Behav 97(1):125–146

    Article  PubMed  PubMed Central  Google Scholar 

  • Samii A, Nutt JG, Ransom BR (2004) Parkinson’s disease. Lancet 363(9423):1783–1793

    Article  PubMed  Google Scholar 

  • Santiago RM, Barbieiro J, Lima MM et al (2010) Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson’s disease are predominantly associated with serotonin and dopamine. Prog Neuropsychopharmacol Biol Psychiatry 34(6):1104–1114

    Article  PubMed  Google Scholar 

  • Savasta M, Carcenac C, Boulet S (2011) Mechanisms of high frequency stimulation of the subthalamic nucleus in Parkinson’s disease: from local to distal effects on the basal ganglia network. In: Rana AQ (ed) Diagnosis of Parkinson’s disease

    Google Scholar 

  • Schmidt L, d’Arc BF, Lafargue G et al (2008) Disconnecting force from money: effects of basal ganglia damage on incentive motivation. Brain 131(Pt 5):1303–1310

    PubMed  Google Scholar 

  • Sensi M, Eleopra R, Cavallo MA et al (2004) Explosive-aggressive behavior related to bilateral subthalamic stimulation. Parkinsonism Relat Disord 10(4):247–251

    Article  PubMed  Google Scholar 

  • Sjoerds Z, Luigjes J, van den Brink W et al (2014) The role of habits and motivation in human drug addiction: a reflection. Front Psychiatry 5:8. doi:10.3389/fpsyt.2014.00008

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith Y, Bevan MD, Shink E et al (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86(2):353–387, pii:S0306452298000049

    Article  PubMed  Google Scholar 

  • Sockeel P, Dujardin K, Devos D et al (2006) The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson’s disease. J Neurol Neurosurg Psychiatry 77(5):579–584

    Article  PubMed  PubMed Central  Google Scholar 

  • Sokoloff P, Diaz J, Le Foll B et al (2006) The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets 5(1):25–43

    Article  PubMed  Google Scholar 

  • Soulas T, Gurruchaga JM, Palfi S et al (2008) Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson’s disease. J Neurol Neurosurg Psychiatry 79(8):952–954

    Article  PubMed  Google Scholar 

  • Starkstein SE, Brockman S (2011) Apathy and Parkinson’s disease. Curr Treat Options Neurol 13(3):267–273. doi:10.1007/s11940-011-0118-9

    Article  PubMed  Google Scholar 

  • Starkstein SE, Merello M, Jorge R et al (2009) The syndromal validity and nosological position of apathy in Parkinson’s disease. Mov Disord 24(8):1211–1216. doi:10.1002/mds.22577

    Article  PubMed  Google Scholar 

  • Strafella AP, Sadikot AF, Dagher A (2003) Subthalamic deep brain stimulation does not induce striatal dopamine release in Parkinson’s disease. Neuroreport 14(9):1287–1289. doi:10.1097/01.wnr.0000081873.45938.56

    Article  PubMed  Google Scholar 

  • Tadaiesky MT, Dombrowski PA, Figueiredo CP et al (2008) Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson’s disease. Neuroscience 156(4):830–840. doi:10.1016/j.neuroscience.2008.08.035, pii:S0306-4522(08)01247-5

    Article  PubMed  Google Scholar 

  • Tan SK, Hartung H, Visser-Vandewalle V et al (2012) A combined in vivo neurochemical and electrophysiological analysis of the effect of high-frequency stimulation of the subthalamic nucleus on 5-HT transmission. Exp Neurol 233(1):145–153

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Temel Y (2010) Limbic effects of high-frequency stimulation of the subthalamic nucleus. Vitam Horm 82:47–63

    Article  PubMed  Google Scholar 

  • Temel Y, Visser-Vandewalle V, Aendekerk B et al (2005) Acute and separate modulation of motor and cognitive performance in parkinsonian rats by bilateral stimulation of the subthalamic nucleus. Exp Neurol 193(1):43–52

    Article  PubMed  Google Scholar 

  • Temel Y, Kessels A, Tan S et al (2006) Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Parkinsonism Relat Disord 12(5):265–272

    Article  PubMed  Google Scholar 

  • Temel Y, Boothman LJ, Blokland A et al (2007) Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc Natl Acad Sci U S A 104(43):17087–17092

    Article  PubMed  PubMed Central  Google Scholar 

  • Temel Y, Tan S, Vlamings R et al (2009) Cognitive and limbic effects of deep brain stimulation in preclinical studies. Front Biosci (Landmark Ed) 14:1891–1901

    Article  Google Scholar 

  • Thobois S, Ardouin C, Lhommee E et al (2010) Non-motor dopamine withdrawal syndrome after surgery for Parkinson’s disease: predictors and underlying mesolimbic denervation. Brain 133(Pt 4):1111–1127

    Article  PubMed  Google Scholar 

  • Tong ZY, Kingsbury AE, Foster OJ (2000) Up-regulation of tyrosine hydroxylase mRNA in a sub-population of A10 dopamine neurons in Parkinson’s disease. Brain Res Mol Brain Res 79(1-2):45–54, pii:S0169328X00000899

    Article  PubMed  Google Scholar 

  • Torack RM, Morris JC (1988) The association of ventral tegmental area histopathology with adult dementia. Arch Neurol 45(5):497–501

    Article  PubMed  Google Scholar 

  • Tran AH, Tamura R, Uwano T et al (2002) Altered accumbens neural response to prediction of reward associated with place in dopamine D2 receptor knockout mice. Proc Natl Acad Sci U S A 99(13):8986–8991

    Article  PubMed  PubMed Central  Google Scholar 

  • Troster AI (2009) Neuropsychology of deep brain stimulation in neurology and psychiatry. Front Biosci (Landmark Ed) 14:1857–1879, pii:3347

    Article  Google Scholar 

  • Ulla M, Thobois S, Llorca PM et al (2011) Contact dependent reproducible hypomania induced by deep brain stimulation in Parkinson’s disease: clinical, anatomical and functional imaging study. J Neurol Neurosurg Psychiatry 82(6):607–614

    Article  PubMed  Google Scholar 

  • Ungerstedt U (1971) Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:95–122

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • van Duijn E, Kingma EM, van der Mast RC (2007) Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci 19(4):441–448

    Article  PubMed  Google Scholar 

  • Vitek JL (2002) Mechanisms of deep brain stimulation: excitation or inhibition. Mov Disord 17(Suppl 3):S69–S72. doi:10.1002/mds.10144

    Article  PubMed  Google Scholar 

  • Volkmann J, Daniels C, Witt K (2010) Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease. Nat Rev Neurol 6(9):487–498

    PubMed  Google Scholar 

  • Volkow ND, Baler RD, Goldstein RZ (2011a) Addiction: pulling at the neural threads of social behaviors. Neuron 69(4):599–602

    Article  PubMed  PubMed Central  Google Scholar 

  • Volkow ND, Wang GJ, Newcorn JH et al (2011b) Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. Mol Psychiatry 16(11):1147–1154

    Article  PubMed  Google Scholar 

  • Voon V, Kubu C, Krack P et al (2006) Deep brain stimulation: neuropsychological and neuropsychiatric issues. Mov Disord 21(Suppl 14):S305–S327. doi:10.1002/mds.20963

    Article  PubMed  Google Scholar 

  • Voon V, Krack P, Lang AE et al (2008) A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain 131(Pt 10):2720–2728

    Article  PubMed  PubMed Central  Google Scholar 

  • Voon V, Mehta AR, Hallett M (2011) Impulse control disorders in Parkinson’s disease: recent advances. Curr Opin Neurol 24(4):324–330. doi:10.1097/WCO.0b013e3283489687

    Article  PubMed  PubMed Central  Google Scholar 

  • Weintraub D, Newberg AB, Cary MS et al (2005) Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson’s disease. J Nucl Med 46(2):227–232. pii:46/2/227

    Google Scholar 

  • WHO (2010) International statistical classification of diseases and related health problems 10th revision (ICD-10) version for 2010. In: World Health Organization (ed)

    Google Scholar 

  • Winstanley CA, Baunez C, Theobald DE et al (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

    Article  PubMed  Google Scholar 

  • Winter C, von Rumohr A, Mundt A et al (2007) Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats. Behav Brain Res 184(2):133–141

    Article  PubMed  Google Scholar 

  • Winter C, Lemke C, Sohr R et al (2008) High frequency stimulation of the subthalamic nucleus modulates neurotransmission in limbic brain regions of the rat. Exp Brain Res 185(3):497–507. doi:10.1007/s00221-007-1171-1

    Article  PubMed  Google Scholar 

  • Wise RA (1973) Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacologia 29(3):203–210

    Article  PubMed  Google Scholar 

  • Wise RA (2009) Roles for nigrostriatal—not just mesocorticolimbic—dopamine in reward and addiction. Trends Neurosci 32(10):517–524

    Article  PubMed  PubMed Central  Google Scholar 

  • Witjas T, Baunez C, Henry JM, Delfini M, Regis J et al (2005) Addiction in Parkinson’s disease: impact of subthalamic nucleus deep brain stimulation. Mov Disord 20(8):1052–1055. doi:10.1002/mds.20501

    Article  PubMed  Google Scholar 

  • Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nat Rev Neurosci 7(6):464–476

    Article  PubMed  Google Scholar 

  • York MK, Dulay M, Macias A et al (2008) Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 79(7):789–795

    Article  PubMed  Google Scholar 

  • Zhao XD, Cao YQ, Liu HH et al (2009) Long term high frequency stimulation of STN increases dopamine in the corpus striatum of hemiparkinsonian rhesus monkey. Brain Res 1286:230–238

    Article  PubMed  Google Scholar 

  • Zis AP, Fibiger HC, Phillips AG (1974) Reversal by L-dopa of impaired learning due to destruction of the dopaminergic nigro-neostriatal projection. Science 185(4155):960–962

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Institut National de la Santé et de la Recherche Médicale, Fondation NeuroDis, Association France Parkinson, Ministère de la Recherche et de la Technologie (MRT), Région Rhône-Alpes (ARC 2), Fondation de France, Agence nationale de la recherche (ANR13 SAMA001401), and Grenoble Alpes University.

S.C., S.B. wrote the chapter with the help of the other authors C.C. and M.S.

Conflicts of Interest none.

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Authors and Affiliations

  1. INSERM U1216, 38000, Grenoble, France

    Sabrina Boulet Ph.D., Carole Carcenac Ph.D., Marc Savasta Ph.D. & Sébastien Carnicella Ph.D.

  2. GIN, Université Grenoble Alpes, 38000, Grenoble, France

    Sabrina Boulet Ph.D., Carole Carcenac Ph.D., Marc Savasta Ph.D. & Sébastien Carnicella Ph.D.

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  1. Sabrina Boulet Ph.D.
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Correspondence to Sabrina Boulet Ph.D. .

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  1. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, USA

    Jean-Jacques Soghomonian

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Boulet, S., Carcenac, C., Savasta, M., Carnicella, S. (2016). Motivational Deficits in Parkinson’s Disease: Role of the Dopaminergic System and Deep-Brain Stimulation of the Subthalamic Nucleus. In: Soghomonian, JJ. (eds) The Basal Ganglia. Innovations in Cognitive Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-42743-0_16

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