Abstract
Our understanding of the neural mechanisms underlying the placebo effect has increased exponentially in parallel with the advances in brain imaging. This is of particular importance in the field of Parkinson’s disease, where clinicians have described placebo effects in their patients for decades. Significant placebo effects have been observed in clinical trials for medications as well as more invasive surgical trials including deep-brain stimulation and stem-cell implantation. In addition to placebo effects occurring as a byproduct of randomized controlled trials, investigation of the placebo effect itself in the laboratory setting has further shown the capacity for strong placebo effects within this patient population. Neuroimaging studies have demonstrated that placebos stimulate the release of dopamine in the striatum of patients with Parkinson’s disease and can alter the activity of dopamine neurons using single-cell recording. When taken together with the findings from other medical conditions discussed elsewhere in this publication, a unified mechanism for the placebo effect in Parkinson’s disease is emerging that blends expectation-induced neurochemical changes and disease-specific nigrostriatal dopamine release.
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References
Benedetti F (2010) No prefrontal control, no placebo response. Pain 148(3):357–358
Benedetti F (2012) Placebo-induced improvements: how therapeutic rituals affect the patient’s brain. J Acupunct Meridian Stud 5(3):97–103
Benedetti F (2013) Placebo and the new physiology of the doctor-patient relationship. Physiol Rev 93(3):1207–1246
Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I (2003) Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 23(10):4315–4323
Benedetti F, Colloca L, Torre E, Lanotte M, Melcarne A, Pesare M, Bergamasco B, Lopiano L (2004) Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nat Neurosci 7(6):587–588
Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, Asteggiano G (2006) Loss of expectation-related mechanisms in Alzheimer’s disease makes analgesic therapies less effective. Pain 121(1–2):133–144
Bishop MP, Elder ST, Heath RG (1963) Intracranial self-stimulation in man. Science 140:394–396
Breiter HC, Rosen BR (1999) Functional magnetic resonance imaging of brain reward circuitry in the human. Ann N Y Acad Sci 877:523–547
Calne SM, Lidstone SC, Kumar A (2008) Psychosocial issues in young-onset Parkinson’s disease: current research and challenges. Parkinsonism Relat Disord 14(2):143–150
Colloca L, Lopiano L, Lanotte M, Benedetti F (2004) Overt versus covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurol 3(11):679–684
de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ (2001) Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science 293(5532):1164–1166
de la Fuente-Fernandez R, Phillips AG, Zamburlini M, Sossi V, Calne DB, Ruth TJ, Stoessl AJ (2002) Dopamine release in human ventral striatum and expectation of reward. Behav Brain Res 136(2):359–363
de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2004) Placebo mechanisms and reward circuitry: clues from Parkinson’s disease. Biol Psychiatry 56(2):67–71
Diamond SG, Markham CH, Treciokas LJ (1985) Double-blind trial of pergolide for Parkinson’s disease. Neurology 35(3):291–295
Dreher JC, Kohn P, Berman KF (2006) Neural coding of distinct statistical properties of reward information in humans. Cereb Cortex 16:561–573
Fiorillo CD, Tobler PN, Schultz W (2003) Discrete coding of reward probability and uncertainty by dopamine neurons. Science 299(5614):1898–1902
Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344(10):710–719
Goetz CG, Leurgans S, Raman R (2002a) Objective changes in motor function during placebo treatment in PD. Neurology 54(3):710–714
Goetz CG, Leurgans S, Raman R (2002b) Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson’s disease. Mov Disord 12(2):283–288
Haber SN, Fudge JL (1997) The primate substantia nigra and VTA: integrative circuitry and function. Crit Rev Neurobiol 11(4):323–342
Horvitz JC (2000) Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events. Neuroscience 96:651–656
Koepp MJ, Gunn RN, Lawrence AD, Cunningham VJ, Dagher A, Jones T, Brooks DJ, Bench CJ, Grasby PM (1998) Evidence for striatal dopamine release during a video game. Nature 393:266–268
Lanotte M, Lopiano L, Torre E, Bergamasco B, Colloca L, Benedetti F (2005) Expectation enhances autonomic responses to stimulation of the human subthalamic limbic region. Brain Behav Immun 19(6):500–509
Lidstone SC, Stoessl AJ (2007) Understanding the placebo effect: contributions from neuroimaging. Mol Imaging Biol 9(4):176–185
Lidstone SC, Schulzer M, Dinelle K, Mak E, Sossi V, Ruth TJ, Fuente-Fernandez R, Phillips AG, Stoessl AJ (2010) Effects of expectation on placebo-induced dopamine release in Parkinson disease. Arch Gen Psychiatry 67(8):857–865
Ljungberg T, Apicella P, Schultz W (1992) Responses of monkey dopamine neurons during learning of behavioral reactions. J Neurophysiol 67:145–163
McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, Dillon S, Winfield H, Bjugstad KB, Freed CR (2004) Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 61(4):412–420
Mercado R, Constantoyannis C, Mandat T, Kumar A, Schulzer M, Stoessl AJ, Honey CR (2006) Expectation and the placebo effect in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation. Mov Disord 21(9):1457–1461
Mirenowicz J, Schultz W (1994) Importance of unpredictability for reward responses in primate dopamine neurons. J Neurophysiol 72:1024–1027
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54(3):403–414
Olds J, 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
Pollo A, Torre E, Lopiano L, Rizzone M, Lanotte M, Cavanna A, Bergamasco B, Benedetti F (2002) Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients. NeuroReport 13(11):1383–1386
Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80(1):1–27
Schultz W (2000) Multiple reward signals in the brain. Nat Rev Neurosci 1:199–207
Schultz W (2001) Reward signaling by dopamine neurons. Neuroscientist 7(4):293–302
Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK (2007) Individual differences in reward responding explain placebo-induced expectations and effects. Neuron 55(2):325–336
Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK (2008) Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 65(2):220–231
Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D (1999) The placebo response in Parkinson’s disease. Parkinson Study Group. Clin Neuropharmacol 22(4):207–212
Small DM, Jones-Gotman M, Dagher A (2003) Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. NeuroImage 19:1709–1715
Strafella AP, Ko JH, Monchi O (2006) Therapeutic application of transcranial magnetic stimulation in Parkinson’s disease: the contribution of expectation. NeuroImage 31(4):1666–1672
Tobler PN, Fiorillo CD, Schultz W (2005) Adaptive coding of reward value by dopamine neurons. Science 307(5715):1642–1645
Watts RL, Freeman TB, Hauser RA, Bakay RAE, Ellias SA, Stoessl AJ, Eidelberg D, Fink JS (2001) A double-blind, randomised, controlled, multicenter clinical trial of the safety and efficacy of stereotaxic intrastriatal implantation of fetal porcine ventral mesencephalic tissue (NeurocellTM-PD) vs. imitation surgery in patients with Parkinson’s disease (PD). Parkinsonism Relat Disord 7(S87)
Zald DH, Boileau I, El Dearedy W, Gunn R, McGlone F, Dichter GS, Dagher A (2004) Dopamine transmission in the human striatum during monetary reward tasks. J Neurosci 24:4105–4112
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Lidstone, S.C. (2014). Great Expectations: The Placebo Effect in Parkinson’s Disease. In: Benedetti, F., Enck, P., Frisaldi, E., Schedlowski, M. (eds) Placebo. Handbook of Experimental Pharmacology, vol 225. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44519-8_8
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DOI: https://doi.org/10.1007/978-3-662-44519-8_8
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