Brain Mechanisms of the Placebo Effect: An Affective Appraisal Account.

Placebos are sham medical treatments. Nonetheless, they can have substantial effects on clinical outcomes. Placebos depend on a person's psychological and brain responses to the treatment context, which influence appraisals of future well-being. Appraisals are flexible cognitive evaluations of the personal meaning of events and situations that can directly impact symptoms and physiology. They also shape associative learning processes by guiding what is learned from experience. Appraisals are supported by a core network of brain regions associated with the default mode network involved in self-generated emotion, self-evaluation, thinking about the future, social cognition, and valuation of rewards and punishment. Placebo treatments for acute pain and a range of clinical conditions engage this same network of regions, suggesting that placebos affect behavior and physiology by changing how a person evaluates their future well-being and the personal significance of their symptoms.

[1]  W. Brown,et al.  The persistence of the placebo response in antidepressant clinical trials. , 2008, Journal of psychiatric research.

[2]  P. Jerabek,et al.  The functional neuroanatomy of the placebo effect. , 2002, The American journal of psychiatry.

[3]  Tor D. Wager,et al.  The neuroscience of placebo effects: connecting context, learning and health , 2015, Nature Reviews Neuroscience.

[4]  F. Van Overwalle Social cognition and the brain: A meta‐analysis , 2009, Human brain mapping.

[5]  C. Büchel,et al.  Placebo Analgesia: A Predictive Coding Perspective , 2014, Neuron.

[6]  W. Schultz,et al.  Relative reward preference in primate orbitofrontal cortex , 1999, Nature.

[7]  Fabrizio Benedetti,et al.  A comprehensive review of the placebo effect: recent advances and current thought. , 2008, Annual review of psychology.

[8]  C. N. Macrae,et al.  Finding the Self? An Event-Related fMRI Study , 2002, Journal of Cognitive Neuroscience.

[9]  H. Flor,et al.  Treatment history and placebo responses to experimental and clinical pain in chronic pain patients , 2016, European journal of pain.

[10]  A. Leuchter,et al.  Changes in brain function of depressed subjects during treatment with placebo. , 2002, The American journal of psychiatry.

[11]  R. Bandler,et al.  Parallel circuits mediating distinct emotional coping reactions to different types of stress , 2001, Neuroscience & Biobehavioral Reviews.

[12]  S. Blakemore The social brain in adolescence , 2008, Nature Reviews Neuroscience.

[13]  A. Kazdin,et al.  The impact of variations in treatment rationales on expectancies for therapeutic change , 1983 .

[14]  T. Schnitzer,et al.  Brain networks predicting placebo analgesia in a clinical trial for chronic back pain , 2012, PAIN®.

[15]  G. Berntson,et al.  The decerebrate human: Associative learning , 1983, Experimental Neurology.

[16]  D. Ramsay,et al.  Pavlovian influences over food and drug intake , 2000, Behavioural Brain Research.

[17]  Brandall Y. Suyenobu,et al.  The neural correlates of placebo effects: a disruption account , 2004, NeuroImage.

[18]  Domenica Le Pera,et al.  Learning potentiates neurophysiological and behavioral placebo analgesic responses , 2008, PAIN.

[19]  Justin L. Vincent,et al.  Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity. , 2008, Journal of neurophysiology.

[20]  Fabrizio Benedetti,et al.  New Insights into the Placebo and Nocebo Responses , 2008, Neuron.

[21]  Kristen A. Lindquist,et al.  The brain basis of emotion: A meta-analytic review , 2012, Behavioral and Brain Sciences.

[22]  Russell A. Poldrack,et al.  Large-scale automated synthesis of human functional neuroimaging data , 2011, Nature Methods.

[23]  Fabrizio Benedetti,et al.  Open versus hidden medical treatments: The patient's knowledge about a therapy affects the therapy outcome. , 2003 .

[24]  C. Padoa-Schioppa Neurobiology of economic choice: a good-based model. , 2011, Annual review of neuroscience.

[25]  Scott T. Grafton,et al.  Wandering Minds: The Default Network and Stimulus-Independent Thought , 2007, Science.

[26]  A. Hrõbjartsson,et al.  Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups , 2009, BMJ : British Medical Journal.

[27]  Chris C. Tang,et al.  Network modulation following sham surgery in Parkinson's disease. , 2014, The Journal of clinical investigation.

[28]  Lisa Feldman Barrett,et al.  Emotions are real. , 2012, Emotion.

[29]  T. Kaptchuk,et al.  To what extent are surgery and invasive procedures effective beyond a placebo response? A systematic review with meta-analysis of randomised, sham controlled trials , 2015, BMJ Open.

[30]  R. Saunders,et al.  Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating , 2013, Nature Neuroscience.

[31]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[32]  A. Hrõbjartsson,et al.  A systematic review found no consistent difference in effect between more and less intensive placebo interventions. , 2015, Journal of clinical epidemiology.

[33]  B. Dick,et al.  Enhanced Therapeutic Alliance Modulates Pain Intensity and Muscle Pain Sensitivity in Patients With Chronic Low Back Pain: An Experimental Controlled Study , 2013, Physical Therapy.

[34]  K. Wiech,et al.  The Effect of Treatment History on Therapeutic Outcome: Psychological and Neurobiological Underpinnings , 2014, PloS one.

[35]  Elliot T. Berkman,et al.  Evidence for social working memory from a parametric functional MRI study , 2012, Proceedings of the National Academy of Sciences.

[36]  C. Frith,et al.  Meeting of minds: the medial frontal cortex and social cognition , 2006, Nature Reviews Neuroscience.

[37]  G. Keitner,et al.  A reevaluation of the exclusion criteria used in antidepressant efficacy trials. , 2002, The American journal of psychiatry.

[38]  T. Wager,et al.  Brain Predictors of Individual Differences in Placebo Responding , 2013 .

[39]  R. Buckner,et al.  Self-projection and the brain , 2007, Trends in Cognitive Sciences.

[40]  F. Schneier,et al.  INFLUENCE OF STUDY DESIGN ON TREATMENT RESPONSE IN ANXIETY DISORDER CLINICAL TRIALS , 2015, Depression and anxiety.

[41]  J. Lieberman,et al.  Placebo response in antipsychotic clinical trials: a meta-analysis. , 2014, JAMA psychiatry.

[42]  Jason P. Mitchell,et al.  Repetition suppression of ventromedial prefrontal activity during judgments of self and others , 2008, Proceedings of the National Academy of Sciences.

[43]  G. Schoenbaum,et al.  What the orbitofrontal cortex does not do , 2015, Nature Neuroscience.

[44]  K. Wiech,et al.  The effect of treatment history on therapeutic outcome: an experimental approach. , 2013, JAMA internal medicine.

[45]  Erin Kendall Braun,et al.  Mind matters: Placebo enhances reward learning in Parkinson’s disease , 2014, Nature Neuroscience.

[46]  K. Berridge,et al.  Instant Transformation of Learned Repulsion into Motivational “Wanting” , 2013, Current Biology.

[47]  Ajay B. Satpute,et al.  The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature. , 2016, Cerebral cortex.

[48]  J. Grau Learning from the spinal cord: How the study of spinal cord plasticity informs our view of learning , 2014, Neurobiology of Learning and Memory.

[49]  Craig A. Smith,et al.  Patterns of cognitive appraisal in emotion. , 1985, Journal of personality and social psychology.

[50]  Sara E. Morrison,et al.  Different Time Courses for Learning-Related Changes in Amygdala and Orbitofrontal Cortex , 2011, Neuron.

[51]  Ted J. Kaptchuk,et al.  Components of Placebo Effect: Randomised Controlled Trial in Patients with Irritable Bowel Syndrome , 2010 .

[52]  Igor Sorokin,et al.  Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials , 2015, Current Urology Reports.

[53]  K. Meissner The placebo effect and the autonomic nervous system: evidence for an intimate relationship , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[54]  S. Langenecker,et al.  Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. , 2015, JAMA psychiatry.

[55]  S. Folkman,et al.  Stress, appraisal, and coping , 1974 .

[56]  Vesna Sossi,et al.  Effects of expectation on placebo-induced dopamine release in Parkinson disease. , 2010, Archives of general psychiatry.

[57]  R. DeRubeis,et al.  Antidepressant drug effects and depression severity: a patient-level meta-analysis. , 2010, JAMA.

[58]  L. Colloca,et al.  How placebo responses are formed: a learning perspective , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[59]  D. Shohamy,et al.  Ventromedial prefrontal-subcortical systems and the generation of affective meaning , 2012, Trends in Cognitive Sciences.

[60]  Robert A Koeppe,et al.  Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. , 2008, Archives of general psychiatry.

[61]  F. Benedetti Placebo Effects: From the Neurobiological Paradigm to Translational Implications , 2014, Neuron.

[62]  N. Volkow,et al.  Addiction: Beyond dopamine reward circuitry , 2011, Proceedings of the National Academy of Sciences.

[63]  Steve Stewart-Williams,et al.  The placebo effect: dissolving the expectancy versus conditioning debate. , 2004, Psychological bulletin.

[64]  Betty Chewning,et al.  Perception of empathy in the therapeutic encounter: effects on the common cold. , 2011, Patient education and counseling.

[65]  F. Benedetti,et al.  Placebo analgesia , 2006, Neurological Sciences.

[66]  Timothy E. J. Behrens,et al.  Organizing conceptual knowledge in humans with a gridlike code , 2016, Science.

[67]  J. O'Doherty,et al.  Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex , 2003, Science.

[68]  F. Benedetti,et al.  Role of explicit verbal information in conditioned analgesia , 2015, European journal of pain.

[69]  A. Soltani,et al.  Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers , 2016, Front. Psychiatry.

[70]  I. Kirsch,et al.  Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome , 2010, PloS one.

[71]  Lisa Feldman Barrett,et al.  Grounding emotion in situated conceptualization , 2011, Neuropsychologia.

[72]  Martin A Lindquist,et al.  Dissociable Influences of Opiates and Expectations on Pain , 2012, The Journal of Neuroscience.

[73]  T. Wager,et al.  Beyond conformity: Social influences on pain reports and physiology. , 2016, Emotion.

[74]  A. Canbay,et al.  Behavioral conditioning of immunosuppression is possible in humans , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[75]  Gary G. Berntson,et al.  Organization of brainstem behavioral systems , 1976, Brain Research Bulletin.

[76]  G. Rücker,et al.  Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. , 2013, JAMA internal medicine.

[77]  M. Schedlowski,et al.  The learned immune response: Pavlov and beyond , 2010, Brain, Behavior, and Immunity.

[78]  Pascal Tétreault,et al.  Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials , 2016, PLoS biology.

[79]  P. Petrovic,et al.  How the number of learning trials affects placebo and nocebo responses , 2010, PAIN®.

[80]  A. Etkin,et al.  Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. , 2007, The American journal of psychiatry.

[81]  M Schulzer,et al.  Expectation and Dopamine Release: Mechanism of the Placebo Effect in Parkinson's Disease , 2001, Science.

[82]  Thomas E. Nichols,et al.  A Bayesian Model of Category-Specific Emotional Brain Responses , 2015, PLoS Comput. Biol..

[83]  Luana Colloca,et al.  Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus , 2004, Nature Neuroscience.

[84]  Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. , 1991 .

[85]  U. Mitzdorf,et al.  Evidence for placebo effects on physical but not on biochemical outcome parameters: a review of clinical trials , 2007, BMC medicine.

[86]  M. Rowbotham,et al.  Placebo response in neuropathic pain trials , 2008, PAIN.

[87]  Colin Camerer,et al.  Dissociating the Role of the Orbitofrontal Cortex and the Striatum in the Computation of Goal Values and Prediction Errors , 2008, The Journal of Neuroscience.

[88]  Wael El-Deredy,et al.  Reproducibility of placebo analgesia: Effect of dispositional optimism , 2009, PAIN.

[89]  K. Krishnan,et al.  Magnitude of placebo response and drug–placebo differences across psychiatric disorders , 2004, Psychological Medicine.

[90]  D. Hoaglin,et al.  Altered Placebo and Drug Labeling Changes the Outcome of Episodic Migraine Attacks , 2014, Science Translational Medicine.

[91]  K. Berridge,et al.  Affective neuroscience of pleasure: reward in humans and animals , 2008, Psychopharmacology.

[92]  James V Haxby,et al.  The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing , 2016, The Journal of Neuroscience.

[93]  F. Overwalle Social cognition and the brain: a meta-analysis. , 2009 .

[94]  E. Israel,et al.  Active albuterol or placebo, sham acupuncture, or no intervention in asthma. , 2011, The New England journal of medicine.

[95]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[96]  C. Marmar,et al.  Impact of confirming patient expectations of change processes in behavioral, cognitive, and brief dynamic psychotherapy. , 1989 .

[97]  A. LaCroix,et al.  Placebo Improvement in Pharmacologic Treatment of Menopausal Hot Flashes: Time Course, Duration, and Predictors , 2015, Psychosomatic medicine.

[98]  F. Benedetti,et al.  Teaching neurons to respond to placebos , 2016, The Journal of physiology.

[99]  L. F. Barrett The Conceptual Act Theory: A Précis , 2014 .

[100]  F. Benedetti,et al.  The role of learning in nocebo and placebo effects , 2008, PAIN.

[101]  Wolfgang M. Pauli,et al.  Regional specialization within the human striatum for diverse psychological functions , 2016, Proceedings of the National Academy of Sciences.

[102]  K. Scherer Appraisal considered as a process of multilevel sequential checking. , 2001 .

[103]  J. Smoller,et al.  Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association , 2013, PloS one.

[104]  Christian Büchel,et al.  Cortical and subcortical responses to high and low effective placebo treatments , 2013, NeuroImage.

[105]  R. Herrnstein Placebo Effect in the Rat , 1962, Science.

[106]  W. Piper,et al.  Expectancy, the therapeutic alliance, and treatment outcome in short-term individual psychotherapy. , 1998, The Journal of psychotherapy practice and research.

[107]  R. DeRubeis,et al.  Antidepressant Drug Effects and Depression Severity , 2022 .

[108]  J. Zubieta,et al.  Placebo effects on human μ-opioid activity during pain , 2007, Proceedings of the National Academy of Sciences.

[109]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[110]  Irving Kirsch,et al.  Response expectancy as a determinant of experience and behavior. , 1985 .

[111]  C. Büchel,et al.  Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia , 2009, Neuron.

[112]  Sylvia A. Morelli,et al.  The neural bases of feeling understood and not understood. , 2014, Social cognitive and affective neuroscience.

[113]  Jason P. Mitchell,et al.  Medial prefrontal cortex subserves diverse forms of self-reflection , 2011, Social neuroscience.

[114]  Jason G. Craggs,et al.  Enhancing the placebo response: functional magnetic resonance imaging evidence of memory and semantic processing in placebo analgesia. , 2014, The journal of pain : official journal of the American Pain Society.

[115]  David Rindskopf,et al.  Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. , 2008, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[116]  R. N. Spreng,et al.  The default network and self‐generated thought: component processes, dynamic control, and clinical relevance , 2014, Annals of the New York Academy of Sciences.

[117]  Raveendhara R. Bannuru,et al.  Effectiveness and Implications of Alternative Placebo Treatments , 2015, Annals of Internal Medicine.

[118]  Edward E. Smith,et al.  Anticipation and Experience of Pain Placebo-Induced Changes in fMRI in the , 2007 .

[119]  G. Zaccara,et al.  Placebo and nocebo responses in drug trials of epilepsy , 2015, Epilepsy & Behavior.

[120]  F. Benedetti,et al.  Conscious Expectation and Unconscious Conditioning in Analgesic, Motor, and Hormonal Placebo/Nocebo Responses , 2003, The Journal of Neuroscience.

[121]  C. Frith,et al.  The Neural Basis of Mentalizing , 2006, Neuron.

[122]  Jessica A. Keith Patient Predictors of Response to Interpersonal Psychotherapy (IPT) for Depression , 2006 .

[123]  T. Wager,et al.  Conceptual Conditioning , 2015, Psychological science.

[124]  J. O'Doherty,et al.  Evidence for a Common Representation of Decision Values for Dissimilar Goods in Human Ventromedial Prefrontal Cortex , 2009, The Journal of Neuroscience.

[125]  C. Büchel,et al.  Neural Mechanisms of Placebo Anxiolysis , 2016 .

[126]  William W. Graves,et al.  Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. , 2009, Cerebral cortex.

[127]  K. O'malley,et al.  A controlled trial of arthroscopic surgery for osteoarthritis of the knee. , 2002, The New England journal of medicine.

[128]  Jason G. Craggs,et al.  The dynamic mechanisms of placebo induced analgesia: Evidence of sustained and transient regional involvement , 2008, PAIN.

[129]  Kevin N. Ochsner,et al.  A Meta-analysis of Functional Neuroimaging Studies of Self- and Other Judgments Reveals a Spatial Gradient for Mentalizing in Medial Prefrontal Cortex , 2012, Journal of Cognitive Neuroscience.

[130]  Jin Fan,et al.  Somatic and vicarious pain are represented by dissociable multivariate brain patterns , 2016, eLife.

[131]  Fabrizio Benedetti,et al.  The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect , 2006, The Journal of Neuroscience.

[132]  Angela R. Laird,et al.  Activation likelihood estimation meta-analysis revisited , 2012, NeuroImage.

[133]  M. Shea,et al.  Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. , 1991, The American journal of psychiatry.

[134]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[135]  Christian Büchel,et al.  Direct Evidence for Spinal Cord Involvement in Placebo Analgesia , 2009, Science.

[136]  J. Jankovic,et al.  Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double‐blind, randomized, controlled trial , 2015, Annals of neurology.

[137]  D. Wedekind,et al.  Efficacy of treatments for anxiety disorders: a meta-analysis , 2015, International clinical psychopharmacology.

[138]  A. Kiss,et al.  Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses. , 2010, The Journal of clinical psychiatry.

[139]  Maurizio Fava,et al.  Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD , 2009, European Neuropsychopharmacology.

[140]  Christian F. Doeller,et al.  Evidence for grid cells in a human memory network , 2010, Nature.

[141]  Andrew Ortony,et al.  The Cognitive Structure of Emotions , 1988 .

[142]  Luana Colloca,et al.  Overt versus covert treatment for pain, anxiety, and Parkinson's disease , 2004, The Lancet Neurology.

[143]  R. DeRubeis,et al.  Patients' competence in and performance of cognitive therapy skills: relation to the reduction of relapse risk following treatment for depression. , 2007, Journal of consulting and clinical psychology.

[144]  Plassmann Hilke,et al.  How Expectancies Shape Consumption Experiences , 2014 .

[145]  T. B. Rogers,et al.  Self-reference and the encoding of personal information. , 1977, Journal of personality and social psychology.

[146]  Donald D. Price,et al.  Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms , 2005, Pain.

[147]  S. Papapetropoulos Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial , 2011 .

[148]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[149]  J. Price Prefrontal Cortical Networks Related to Visceral Function and Mood , 1999, Annals of the New York Academy of Sciences.

[150]  S. Woods,et al.  Control group bias in randomized atypical antipsychotic medication trials for schizophrenia. , 2005, Archives of general psychiatry.

[151]  Franco Cauda,et al.  Activation likelihood estimation meta‐analysis of brain correlates of placebo analgesia in human experimental pain , 2013, Human brain mapping.

[152]  T. Egner,et al.  Emotional processing in anterior cingulate and medial prefrontal cortex , 2011, Trends in Cognitive Sciences.

[153]  Hyoung F. Kim,et al.  Distinct Basal Ganglia Circuits Controlling Behaviors Guided by Flexible and Stable Values , 2013, Neuron.

[154]  T. Wager,et al.  A meta-analysis of brain mechanisms of placebo analgesia: consistent findings and unanswered questions. , 2014, Handbook of experimental pharmacology.

[155]  D. Bartels,et al.  Placebo and nocebo effects in itch and pain. , 2014, Handbook of experimental pharmacology.

[156]  Joseph W. Kable,et al.  The valuation system: A coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value , 2013, NeuroImage.

[157]  J. Neuhaus,et al.  Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST). , 2012, Contemporary clinical trials.

[158]  G. Bennett,et al.  Increasing placebo responses over time in U.S. clinical trials of neuropathic pain , 2015, Pain.

[159]  T. Kaptchuk,et al.  Biological, clinical, and ethical advances of placebo effects , 2010, The Lancet.

[160]  A. Soltani,et al.  Belief about nicotine selectively modulates value and reward prediction error signals in smokers , 2015, Proceedings of the National Academy of Sciences.

[161]  M. Hyland,et al.  Consistency of the placebo effect. , 2008, Journal of psychosomatic research.

[162]  Raffael Kalisch,et al.  A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat , 2010, NeuroImage.

[163]  Harald Merckelbach,et al.  The placebo effect in pain reduction: The influence of conditioning experiences and response expectancies , 1996, International journal of behavioral medicine.

[164]  Jason P. Mitchell,et al.  Dissociable Medial Prefrontal Contributions to Judgments of Similar and Dissimilar Others , 2006, Neuron.

[165]  E. Murray,et al.  The Orbitofrontal Oracle: Cortical Mechanisms for the Prediction and Evaluation of Specific Behavioral Outcomes , 2014, Neuron.

[166]  Yu-Shin Ding,et al.  Expectation Enhances the Regional Brain Metabolic and the Reinforcing Effects of Stimulants in Cocaine Abusers , 2003, The Journal of Neuroscience.

[167]  J. Wallis Orbitofrontal cortex and its contribution to decision-making. , 2007, Annual review of neuroscience.

[168]  Benjamin J. Shannon,et al.  Coherent spontaneous activity identifies a hippocampal-parietal memory network. , 2006, Journal of neurophysiology.

[169]  Alan C. Evans,et al.  Brain Connectivity , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[170]  I. Kirsch,et al.  A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression , 2012, PloS one.

[171]  J. Andrews-Hanna,et al.  Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity. , 2015, JAMA psychiatry.

[172]  B. Peterson,et al.  Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials. , 2017, The American journal of psychiatry.

[173]  E. Murray,et al.  Bilateral Orbital Prefrontal Cortex Lesions in Rhesus Monkeys Disrupt Choices Guided by Both Reward Value and Reward Contingency , 2004, The Journal of Neuroscience.

[174]  G. Andersson,et al.  The efficacy of non-directive supportive therapy for adult depression: a meta-analysis. , 2012, Clinical psychology review.

[175]  Wayne B Jonas,et al.  Deconstructing the Placebo Effect and Finding the Meaning Response , 2002, Annals of Internal Medicine.

[176]  O. Hikosaka,et al.  Two types of dopamine neuron distinctly convey positive and negative motivational signals , 2009, Nature.

[177]  J. Riley,et al.  A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia , 2002, Pain.

[178]  Jamil Zaki,et al.  Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis , 2015, NeuroImage.

[179]  I. Kirsch,et al.  Classical conditioning and the placebo effect , 1997, PAIN.

[180]  E. Kandel,et al.  Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica. , 1983, Science.

[181]  Blair T. Johnson,et al.  Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration , 2008, PLoS medicine.

[182]  James Raiher Conditioned placebo analgesia persists when subjects know they are receiving a placebo , 2015 .

[183]  C. Chapman,et al.  Investigating dose-dependent effects of placebo analgesia: A psychophysiological approach , 2012, PAIN.

[184]  K. Scherer,et al.  Appraisal processes in emotion. , 2003 .

[185]  F. Luo,et al.  Placebo analgesia affects the behavioral despair tests and hormonal secretions in mice , 2011, Psychopharmacology.

[186]  G. Quirk,et al.  Neurons in medial prefrontal cortex signal memory for fear extinction , 2002, Nature.

[187]  S. Leurgans,et al.  Placebo response in Parkinson's disease: Comparisons among 11 trials covering medical and surgical interventions , 2008, Movement disorders : official journal of the Movement Disorder Society.

[188]  Tor D Wager,et al.  Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience , 2011, The Journal of Neuroscience.

[189]  K. Brownell,et al.  Mind over milkshakes: mindsets, not just nutrients, determine ghrelin response. , 2011, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[190]  W. Stiles,et al.  Credibility and outcome of cognitive-behavioural and psychodynamic-interpersonal psychotherapy. , 1995, The British journal of clinical psychology.