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Neuroscience of apathy and anhedonia: a transdiagnostic approach


Apathy and anhedonia are common syndromes of motivation that are associated with a wide range of brain disorders and have no established therapies. Research using animal models suggests that a useful framework for understanding motivated behaviour lies in effort-based decision making for reward. The neurobiological mechanisms underpinning such decisions have now begun to be determined in individuals with apathy or anhedonia, providing an important foundation for developing new treatments. The findings suggest that there might be some shared mechanisms between both syndromes. A transdiagnostic approach that cuts across traditional disease boundaries provides a potentially useful means for understanding these conditions.

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Fig. 1: Mechanisms underlying effort-based decision making to obtain rewards.
Fig. 2: Behavioural paradigms for assessing amotivation.
Fig. 3: Brain regions implicated in motivation, apathy and anhedonia.
Fig. 4: Optogenetic study of effort-based decision making in rodents.


  1. 1.

    Caeiro, L., Ferro, J. M. & Costa, J. Apathy secondary to stroke: a systematic review and meta-analysis. Cerebrovasc. Dis. 35, 23–39 (2013).

    Article  PubMed  Google Scholar 

  2. 2.

    Starkstein, S. E. & Pahissa, J. Apathy following traumatic brain injury. Psychiatr. Clin. North Am. 37, 103–112 (2014).

    Article  PubMed  Google Scholar 

  3. 3.

    Seel, R. T. et al. Depression after traumatic brain injury: a National Institute on Disability and Rehabilitation Research Model Systems multicenter investigation. Arch. Phys. Med. Rehabil. 84, 177–184 (2003).

    Article  PubMed  Google Scholar 

  4. 4.

    Zhao, Q.-F. et al. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: systematic review and meta-analysis. J. Affect. Disord. 190, 264–271 (2016).

    Article  PubMed  Google Scholar 

  5. 5.

    Lopez, O. L. et al. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer’s disease. J. Neuropsychiatry Clin. Neurosci. 15, 346–353 (2003).

    Article  PubMed  Google Scholar 

  6. 6.

    den Brok, M. G. H. E. et al. Apathy in Parkinson’s disease: a systematic review and meta-analysis. Mov. Disord. 30, 759–769 (2015).

    Article  Google Scholar 

  7. 7.

    Lemke, M. R., Brecht, H. M., Koester, J., Kraus, P. H. & Reichmann, H. Anhedonia, depression, and motor functioning in Parkinson’s disease during treatment with pramipexole. J. Neuropsychiatry Clin. Neurosci. 17, 214–220 (2005).

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Staekenborg, S. S. et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J. Neurol. Neurosurg. Psychiatry 81, 547–551 (2010).

    Article  PubMed  Google Scholar 

  9. 9.

    Chow, T. W. et al. Apathy symptom profile and behavioral associations in frontotemporal dementia versus dementia of Alzheimer type. Arch. Neurol. 66, 888–893 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    van Duijn, E. et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J. Neurol. Neurosurg. Psychiatry 85, 1411–1418 (2014).

    Article  PubMed  Google Scholar 

  11. 11.

    Pelizza, L. & Ferrari, A. Anhedonia in schizophrenia and major depression: state or trait? Ann. Gen. Psychiatry 8, 22 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Yuen, G. S. et al. Apathy in late-life depression: common, persistent, and disabling. Am. J. Geriatr. Psychiatry 23, 488–494 (2015).

    Article  PubMed  Google Scholar 

  13. 13.

    Horan, W. P., Kring, A. M. & Blanchard, J. J. Anhedonia in schizophrenia: a review of assessment strategies. Schizophr. Bull. 32, 259–273 (2006).

    Article  PubMed  Google Scholar 

  14. 14.

    Yazbek, H. et al. The Lille Apathy Rating Scale (LARS): exploring its psychometric properties in schizophrenia. Schizophr. Res. 157, 278–284 (2014).

    Article  PubMed  Google Scholar 

  15. 15.

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

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Prange, S. et al. Historical crossroads in the conceptual delineation of apathy in Parkinson’s disease. Brain 141, 613–619 (2018).

    Article  PubMed  Google Scholar 

  17. 17.

    Starkstein, S. E. & Leentjens, A. F. G. The nosological position of apathy in clinical practice. J. Neurol. Neurosurg. Psychiatry 79, 1088–1092 (2008).

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Lanctôt, K. L. et al. Apathy associated with neurocognitive disorders: recent progress and future directions. Alzheimers Dement. 13, 84–100 (2017).

    Article  PubMed  Google Scholar 

  19. 19.

    Robert, P. et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur. Psychiatry 24, 98–104 (2009).

    Article  PubMed  CAS  Google Scholar 

  20. 20.

    Thomsen, K. R., Whybrow, P. C. & Kringelbach, M. L. Reconceptualizing anhedonia: novel perspectives on balancing the pleasure networks in the human brain. Front. Behav. Neurosci. 9, 49 (2015).

    Google Scholar 

  21. 21.

    Foussias, G. & Remington, G. Negative symptoms in schizophrenia: avolition and Occam’s razor. Schizophr. Bull. 36, 359–369 (2010).

    Article  PubMed  Google Scholar 

  22. 22.

    Treadway, M. T. & Zald, D. H. Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci. Biobehav. Rev. 35, 537–555 (2011). This helpful overview provides mechanistic insights on anhedonia in human depression.

    Article  PubMed  Google Scholar 

  23. 23.

    Berridge, K. C. & Robinson, T. E. Parsing reward. Trends Neurosci. 26, 507–513 (2003).

    Article  PubMed  CAS  Google Scholar 

  24. 24.

    Barch, D. M., Pagliaccio, D. & Luking, K. Mechanisms underlying motivational deficits in psychopathology: similarities and differences in depression and schizophrenia. Curr. Top. Behav. Neurosci. 27, 411–449 (2016). This is a comprehensive current review of evidence for possible underlying behavioural components of amotivation across depression and schizophrenia.

    Article  PubMed  Google Scholar 

  25. 25.

    Der-Avakian, A., Barnes, S. A., Markou, A. & Pizzagalli, D. A. Translational assessment of reward and motivational deficits in psychiatric disorders. Curr. Top. Behav. Neurosci. 28, 231–262 (2015). This overview relates animal models to human disorders of motivation in psychiatric diagnoses.

    Article  CAS  Google Scholar 

  26. 26.

    Salamone, J. D., Yohn, S. E., López-Cruz, L., San Miguel, N. & Correa, M. Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology. Brain 139, 1325–1347 (2016). This is a comprehensive review of animal and human experiments investigating the brain mechanisms of effort-related decision making for reward, and how these relate to anhedonia and apathy.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Le Heron, C., Apps, M. A. J. & Husain, M. The anatomy of apathy: a neurocognitive framework for amotivated behaviour. Neuropsychologia (2017). This is a review of neuroimaging studies of apathy across neurological diseases demonstrating many common patterns of regional brain changes.

    Article  PubMed  Google Scholar 

  28. 28.

    Marin, R. S. Apathy: a neuropsychiatric syndrome. J. Neuropsychiatry Clin. Neurosci. 3, 243–254 (1991).

    Article  PubMed  CAS  Google Scholar 

  29. 29.

    Starkstein, S. E., Petracca, G., Chemerinski, E. & Kremer, J. Syndromic validity of apathy in Alzheimer’s disease. Am. J. Psychiatry 158, 872–877 (2001).

    Article  PubMed  CAS  Google Scholar 

  30. 30.

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 31.

    Ang, Y.-S., Lockwood, P., Apps, M. A. J., Muhammed, K. & Husain, M. Distinct subtypes of apathy revealed by the apathy motivation index. PLoS ONE 12, e0169938 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. 32.

    Németh, G., Hegedüs, K. & Molnár, L. Akinetic mutism associated with bicingular lesions: clinicopathological and functional anatomical correlates. Eur. Arch. Psychiatry Neurol. Sci. 237, 218–222 (1988).

    Article  PubMed  Google Scholar 

  33. 33.

    Rizvi, S. J. et al. Development and validation of the Dimensional Anhedonia Rating Scale (DARS) in a community sample and individuals with major depression. Psychiatry Res. 229, 109–119 (2015).

    Article  PubMed  Google Scholar 

  34. 34.

    American Psychiatric Association & American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (American Psychiatric Association, WA, 2013).

  35. 35.

    Shankman, S. A. et al. in Anhedonia: A Comprehensive Handbook Volume 1 (ed. Ritsner, M.) 3–22 (Springer, Netherlands, 2014).

  36. 36.

    Assogna, F., Cravello, L., Caltagirone, C. & Spalletta, G. Anhedonia in Parkinson’s disease: a systematic review of the literature. Mov. Disord. 26, 1825–1834 (2011).

    Article  PubMed  Google Scholar 

  37. 37.

    Blanchard, J. J. & Cohen, A. S. The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr. Bull. 32, 238–245 (2006).

    Article  PubMed  Google Scholar 

  38. 38.

    Foussias, G., Agid, O., Fervaha, G. & Remington, G. Negative symptoms of schizophrenia: clinical features, relevance to real world functioning and specificity versus other CNS disorders. Eur. Neuropsychopharmacol. 24, 693–709 (2014).

    Article  PubMed  CAS  Google Scholar 

  39. 39.

    Kaiser, S. et al. Individual negative symptoms and domains — relevance for assessment, pathomechanisms and treatment. Schizophr. Res. 186, 39–45 (2017).

    Article  PubMed  Google Scholar 

  40. 40.

    Bischof, M. et al. The brief negative symptom scale: validation of the German translation and convergent validity with self-rated anhedonia and observer-rated apathy. BMC Psychiatry 16, 415 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Hartmann, M. N. et al. Apathy in schizophrenia as a deficit in the generation of options for action. J. Abnorm. Psychol. 124, 309–318 (2015). This is one of the few studies that have examined the possibility that a deficit in generating options for behaviour might be associated with apathy in humans.

    Article  PubMed  Google Scholar 

  42. 42.

    Isella, V. et al. Physical anhedonia in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 74, 1308–1311 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. 43.

    Skorvanek, M. et al. The associations between fatigue, apathy, and depression in Parkinson’s disease. Acta Neurol. Scand. 131, 80–87 (2015).

    Article  PubMed  CAS  Google Scholar 

  44. 44.

    Lampe, I. K., Kahn, R. S. & Heeren, T. J. Apathy, anhedonia, and psychomotor retardation in elderly psychiatric patients and healthy elderly individuals. J. Geriatr. Psychiatry Neurol. 14, 11–16 (2001).

    Article  PubMed  CAS  Google Scholar 

  45. 45.

    Brodaty, H., Altendorf, A., Withall, A. & Sachdev, P. Do people become more apathetic as they grow older? A longitudinal study in healthy individuals. Int. Psychogeriatr. 22, 426–436 (2010).

    Article  PubMed  Google Scholar 

  46. 46.

    Bonnelle, V., Manohar, S., Behrens, T. & Husain, M. Individual differences in premotor brain systems underlie behavioral apathy. Cereb. Cortex 26, bhv247 (2016).

    Google Scholar 

  47. 47.

    Lavretsky, H. et al. The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. Int. J. Geriatr. Psychiatry 23, 1040–1050 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Grool, A. M. et al. Structural MRI correlates of apathy symptoms in older persons without dementia: AGES-Reykjavik Study. Neurology 82, 1628–1635 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Kawagoe, T., Onoda, K. & Yamaguchi, S. Apathy and executive function in healthy elderly — resting state fMRI study. Front. Aging Neurosci. 9, 124 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Rzepa, E., Fisk, J. & McCabe, C. Blunted neural response to anticipation, effort and consummation of reward and aversion in adolescents with depression symptomatology. J. Psychopharmacol. 31, 303–311 (2017).

    Article  PubMed  Google Scholar 

  51. 51.

    Pessiglione, M., Vinckier, F., Bouret, S., Daunizeau, J. & Le Bouc, R. Why not try harder? Computational approach to motivation deficits in neuro-psychiatric diseases. Brain (2017).

    Article  PubMed  Google Scholar 

  52. 52.

    Sinha, N., Manohar, S. & Husain, M. Impulsivity and apathy in Parkinson’s disease. J. Neuropsychol. 7, 255–283 (2013).

    Article  PubMed  Google Scholar 

  53. 53.

    Ang, Y.-S. et al. Dopamine modulates option generation for behaviour. Curr. Biol. 28, 1561–1569 (2018).

  54. 54.

    Robinson, G., Shallice, T., Bozzali, M. & Cipolotti, L. The differing roles of the frontal cortex in fluency tests. Brain 135, 2202–2214 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Glimcher, P. W., Fehr, E. & Camerer, C. (eds). Neuroeconomics: Decision Making and The Brain. (Elsevier Academic Press, London, 2014).

    Google Scholar 

  56. 56.

    Le Bouc, R. et al. Computational dissection of dopamine motor and motivational functions in humans. J. Neurosci. 36, 6623–6633 (2016). This study combines empirical findings with computational modelling to pinpoint impaired reward processing in Parkinson's disease.

    Article  PubMed  CAS  Google Scholar 

  57. 57.

    Le Heron, C. et al. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson’s disease. Brain 141, 1455–1469 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Brehm, J. W. & Self, E. A. The intensity of motivation. Annu. Rev. Psychol. 40, 109–131 (1989).

    Article  PubMed  CAS  Google Scholar 

  59. 59.

    Muhammed, K. et al. Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson’s disease. Brain 139, 2706–2721 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Salamone, J. D., Cousins, M. S. & Bucher, S. Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav. Brain Res. 65, 221–229 (1994).

    Article  PubMed  CAS  Google Scholar 

  61. 61.

    Treadway, M. T., Bossaller, N. A., Shelton, R. C. & Zald, D. H. Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J. Abnorm. Psychol. 121, 553–558 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Chong, T. T.-J. et al. Dopamine enhances willingness to exert effort for reward in Parkinson’s disease. Cortex 69, 40–46 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Murray, G. K. et al. Incentive motivation in first-episode psychosis: a behavioural study. BMC Psychiatry 8, 34 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Hosking, J. G., Cocker, P. J. & Winstanley, C. A. Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort. Neuropsychopharmacology 39, 1558–1567 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Schmidt, L., Lebreton, M., Cléry-Melin, M.-L., Daunizeau, J. & Pessiglione, M. Neural mechanisms underlying motivation of mental versus physical effort. PLoS Biol. 10, e1001266 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. 66.

    Chong, T. T.-J. et al. Neurocomputational mechanisms underlying subjective valuation of effort costs. PLoS Biol. 15, e1002598 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. 67.

    Berridge, K. C. & Robinson, T. E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Rev. 28, 309–369 (1998). This landmark experimental paper examines the role of DA in appetitive and consummatory reward processing, providing clear evidence that the former, but not the latter, is disrupted by profound DA depletion.

    Article  PubMed  CAS  Google Scholar 

  68. 68.

    Huys, Q. J. M. et al. The specificity of Pavlovian regulation is associated with recovery from depression. Psychol. Med. 46, 1027–1035 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. 69.

    Willner, P. The chronic mild stress (CMS) model of depression: history, evaluation and usage. Neurobiol. Stress 6, 78–93 (2017).

    Article  PubMed  Google Scholar 

  70. 70.

    Huys, Q. J. M., Daw, N. D. & Dayan, P. Depression: a decision-theoretic analysis. Annu. Rev. Neurosci. 38, 1–23 (2015). This article provides a clear explanation from a computational neuroscience perspective of the different aspects of motivational processing that may underlie depressive symptoms.

    Article  PubMed  CAS  Google Scholar 

  71. 71.

    Bechara, A., Damasio, H., Tranel, D. & Damasio, A. R. Deciding advantageously before knowing the advantageous strategy. Science 275, 1293–1295 (1997).

    Article  PubMed  CAS  Google Scholar 

  72. 72.

    Evens, R., Hoefler, M., Biber, K. & Lueken, U. The Iowa Gambling Task in Parkinson’s disease: a meta-analysis on effects of disease and medication. Neuropsychologia 91, 163–172 (2016).

    Article  PubMed  Google Scholar 

  73. 73.

    Adams, R. A., Huys, Q. J. M. & Roiser, J. P. Computational psychiatry: towards a mathematically informed understanding of mental illness. J. Neurol. Neurosurg. Psychiatry 87, 53–63 (2016).

    Article  PubMed  Google Scholar 

  74. 74.

    Henriques, J. B., Glowacki, J. M. & Davidson, R. J. Reward fails to alter response bias in depression. J. Abnorm. Psychol. 103, 460–466 (1994).

    Article  PubMed  CAS  Google Scholar 

  75. 75.

    Huys, Q. J., Pizzagalli, D. A., Bogdan, R. & Dayan, P. Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis. Biol. Mood Anxiety Disord. 3, 12 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Collins, A. G. E., Brown, J. K., Gold, J. M., Waltz, J. A. & Frank, M. J. Working memory contributions to reinforcement learning impairments in Schizophrenia. J. Neurosci. 34, 13747–13756 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. 77.

    Meyniel, F. et al. A specific role for serotonin in overcoming effort cost. eLife 5, e17282 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Levy, R. & Dubois, B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb. Cortex 16, 916–928 (2005).

    Article  PubMed  Google Scholar 

  79. 79.

    Barris, R. W. & Schuman, H. R. Bilateral anterior cingulate gyrus lesions; syndrome of the anterior cingulate gyri. Neurology 3, 44–52 (1953).

    Article  PubMed  CAS  Google Scholar 

  80. 80.

    Laplane, D. et al. Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study. Brain 112, 699–725 (1989).

    Article  PubMed  Google Scholar 

  81. 81.

    Adam, R. et al. Dopamine reverses reward insensitivity in apathy following globus pallidus lesions. Cortex 49, 1292–1303 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Kang, S. Y. & Kim, J. S. Anterior cerebral artery infarction: stroke mechanism and clinical-imaging study in 100 patients. Neurology 70, 2386–2393 (2008).

    Article  PubMed  Google Scholar 

  83. 83.

    Manohar, S. G. & Husain, M. Human ventromedial prefrontal lesions alter incentivisation by reward. Cortex 76, 104–120 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Heath, R. G. Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm. J. Nerv. Ment. Dis. 154, 3–18 (1972).

    Article  PubMed  CAS  Google Scholar 

  85. 85.

    Berridge, K. C. & Kringelbach, M. L. Pleasure systems in the brain. Neuron 86, 646–664 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. 86.

    Parvizi, J., Rangarajan, V., Shirer, W. R., Desai, N. & Greicius, M. D. The will to persevere induced by electrical stimulation of the human cingulate gyrus. Neuron 80, 1359–1367 (2013).

    Article  PubMed  CAS  Google Scholar 

  87. 87.

    Mayberg, H. S. et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005).

    Article  PubMed  CAS  Google Scholar 

  88. 88.

    Holtzheimer, P. E. et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry 4, 839–849 (2017).

    Article  PubMed  Google Scholar 

  89. 89.

    Rudebeck, P. H., Walton, M. E., Smyth, A. N., Bannerman, D. M. & Rushworth, M. F. S. Separate neural pathways process different decision costs. Nat. Neurosci. 9, 1161–1168 (2006).

    Article  PubMed  CAS  Google Scholar 

  90. 90.

    Walton, M. E., Kennerley, S. W., Bannerman, D. M., Phillips, P. E. M. & Rushworth, M. F. S. Weighing up the benefits of work: behavioral and neural analyses of effort-related decision making. Neural Netw. 19, 1302–1314 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. 91.

    Floresco, S. B. & Ghods-Sharifi, S. Amygdala-prefrontal cortical circuitry regulates effort-based decision making. Cereb. Cortex 17, 251–260 (2007).

    Article  PubMed  Google Scholar 

  92. 92.

    Hauber, W. & Sommer, S. Prefrontostriatal circuitry regulates effort-related decision making. Cereb. Cortex 19, 2240–2247 (2009).

    Article  PubMed  Google Scholar 

  93. 93.

    Worbe, Y. et al. Behavioral and movement disorders induced by local inhibitory dysfunction in primate striatum. Cereb. Cortex 19, 1844–1856 (2009).

    Article  PubMed  Google Scholar 

  94. 94.

    Wise, R. A. Addictive drugs and brain stimulation reward. Annu. Rev. Neurosci. 19, 319–340 (1996).

    Article  PubMed  CAS  Google Scholar 

  95. 95.

    Ferenczi, E. A. et al. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science 351, aac9698 (2016). This pioneering experimental study combines fMRI with simultaneous optogenetic stimulation of both DA and mPFC neurons. Stimulating DA neurons increased (and silencing reduced) vStr responses and reward-seeking behaviour, which was blunted by mPFC stimulation.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. 96.

    Croxson, P. L., Walton, M. E., O’Reilly, J. X., Behrens, T. E. J. & Rushworth, M. F. S. Effort-based cost-benefit valuation and the human brain. J. Neurosci. 29, 4531–4541 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. 97.

    Skvortsova, V., Palminteri, S. & Pessiglione, M. Learning to minimize efforts versus maximizing rewards: computational principles and neural correlates. J. Neurosci. 34, 15621–15630 (2014).

    Article  PubMed  CAS  Google Scholar 

  98. 98.

    Klein-Flugge, M. C., Kennerley, S. W., Friston, K. & Bestmann, S. Neural signatures of value comparison in human cingulate cortex during decisions requiring an effort-reward trade-off. J. Neurosci. 36, 10002–10015 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. 99.

    Zenon, A., Sidibe, M. & Olivier, E. Disrupting the supplementary motor area makes physical effort appear less effortful. J. Neurosci. 35, 8737–8744 (2015).

    Article  PubMed  CAS  Google Scholar 

  100. 100.

    Kroemer, N. B. et al. Balancing reward and work: anticipatory brain activation in NAcc and VTA predict effort differentially. Neuroimage 102, 510–519 (2014).

    Article  PubMed  Google Scholar 

  101. 101.

    Kurniawan, I. T., Guitart-Masip, M., Dayan, P. & Dolan, R. J. Effort and valuation in the brain: the effects of anticipation and execution. J. Neurosci. 33, 6160–6169 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. 102.

    Lau, H. C., Rogers, R. D., Haggard, P. & Passingham, R. E. Attention to intention. Science 303, 1208–1210 (2004).

    Article  PubMed  CAS  Google Scholar 

  103. 103.

    Nachev, P., Kennard, C. & Husain, M. Functional role of the supplementary and pre-supplementary motor areas. Nat. Rev. Neurosci. 9, 856–869 (2008).

    Article  PubMed  CAS  Google Scholar 

  104. 104.

    Pizzagalli, D. A. et al. Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am. J. Psychiatry 166, 702–710 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Knutson, B., Bhanji, J. P., Cooney, R. E., Atlas, L. Y. & Gotlib, I. H. Neural responses to monetary incentives in major depression. Biol. Psychiatry 63, 686–692 (2008).

    Article  PubMed  Google Scholar 

  106. 106.

    Gorka, S. M. et al. Neural response to reward anticipation in those with depression with and without panic disorder. J. Affect. Disord. 164, 50–56 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Rutledge, R. B. et al. Association of neural and emotional impacts of reward prediction errors with major depression. JAMA Psychiatry 74, 790 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Stringaris, A. et al. The brain’s response to reward anticipation and depression in adolescence: dimensionality, specificity, and longitudinal predictions in a community-based sample. Am. J. Psychiatry 172, 1215–1223 (2015).

    Article  PubMed  Google Scholar 

  109. 109.

    Ziauddeen, H. & Murray, G. K. The relevance of reward pathways for schizophrenia. Curr. Opin. Psychiatry 23, 91–96 (2010).

    Article  PubMed  Google Scholar 

  110. 110.

    Zhang, B. et al. Mapping anhedonia-specific dysfunction in a transdiagnostic approach: an ALE meta-analysis. Brain Imaging Behav. 10, 920–939 (2016).

    Article  PubMed  Google Scholar 

  111. 111.

    Howe, M. W., Tierney, P. L., Sandberg, S. G., Phillips, P. E. M. & Graybiel, A. M. Prolonged dopamine signalling in striatum signals proximity and value of distant rewards. Nature 500, 575–579 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. 112.

    Robbins, T. W., Roberts, D. C. & Koob, G. F. Effects of D-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens. J. Pharmacol. Exp. Ther. 224, 662–673 (1983).

    PubMed  CAS  Google Scholar 

  113. 113.

    Taylor, J. R. & Robbins, T. W. Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology. 84, 405–412 (1984).

    Article  PubMed  CAS  Google Scholar 

  114. 114.

    Cador, M., Taylor, J. R. & Robbins, T. W. Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. Psychopharmacoloy 104, 377–385 (1991).

    Article  CAS  Google Scholar 

  115. 115.

    Salamone, J. D. & Correa, M. The mysterious motivational functions of mesolimbic dopamine. Neuron 76, 470–485 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. 116.

    Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997).

    Article  PubMed  CAS  Google Scholar 

  117. 117.

    Chang, C. Y. et al. Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors. Nat. Neurosci. 19, 111–116 (2016).

    Article  PubMed  CAS  Google Scholar 

  118. 118.

    Steinberg, E. E. et al. A causal link between prediction errors, dopamine neurons and learning. Nat. Neurosci. 16, 966–973 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. 119.

    Niv, Y., Daw, N. D., Joel, D. & Dayan, P. Tonic dopamine: opportunity costs and the control of response vigor. Psychopharmacology 191, 507–520 (2007).

    Article  PubMed  CAS  Google Scholar 

  120. 120.

    Hamid, A. A. et al. Mesolimbic dopamine signals the value of work. Nat. Neurosci. 19, 117–126 (2015). In this investigation, microdialysis and voltammetry were used to measure DA release in the NAc. DA levels co-varied with reward rate and motivational vigour, and also encoded value. The authors conclude that DA conveys a signal regarding the available reward for investment of effort.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. 121.

    Syed, E. C. J. et al. Action initiation shapes mesolimbic dopamine encoding of future rewards. Nat. Neurosci. 19, 34–36 (2015). This study used FSCV to demonstrate that DA is released in the vStr when animals are required to make an action to obtain a reward, and that DA release is attenuated when inhibition of movement is required.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. 122.

    Collins, A. G. E. & Frank, M. J. Surprise! Dopamine signals mix action, value and error. Nat. Neurosci. 19, 3–5 (2016).

    Article  PubMed  CAS  Google Scholar 

  123. 123.

    Martins, D., Mehta, M. A. & Prata, D. The “highs and lows” of the human brain on dopaminergics: evidence from neuropharmacology. Neurosci. Biobehav. Rev. 80, 351–371 (2017). This article presents a systematic review of behavioural and neural effects of DA manipulations in humans.

    Article  PubMed  CAS  Google Scholar 

  124. 124.

    Leyton, M. et al. Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine depletion: a PET/[11C]raclopride study in healthy men. Neuropsychopharmacology 29, 427–432 (2003).

    Article  CAS  Google Scholar 

  125. 125.

    Roiser, J. P. et al. The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression. Neuropsychopharmacology 30, 775–785 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. 126.

    Robinson, O. J., Standing, H. R., DeVito, E. E., Cools, R. & Sahakian, B. J. Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males. Psychopharmacology 211, 187–195 (2010).

    Article  PubMed  CAS  Google Scholar 

  127. 127.

    Bjork, J. M., Grant, S. J., Chen, G. & Hommer, D. W. Dietary tyrosine/phenylalanine depletion effects on behavioral and brain signatures of human motivational processing. Neuropsychopharmacology 39, 595–604 (2014).

    Article  PubMed  CAS  Google Scholar 

  128. 128.

    Guitart-Masip, M. et al. Action controls dopaminergic enhancement of reward representations. Proc. Natl Acad. Sci. USA 109, 7511–7516 (2012).

    Article  PubMed  Google Scholar 

  129. 129.

    Zenon, A., Devesse, S. & Olivier, E. Dopamine manipulation affects response vigor independently of opportunity cost. J. Neurosci. 36, 9516–9525 (2016).

    Article  PubMed  CAS  Google Scholar 

  130. 130.

    Rutledge, R. B., Skandali, N., Dayan, P. & Dolan, R. J. Dopaminergic modulation of decision making and subjective well-being. J. Neurosci. 35, 9811–9822 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. 131.

    Chowdhury, R. et al. Dopamine restores reward prediction errors in old age. Nat. Neurosci. 16, 648–653 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. 132.

    Argyropoulos, S. V. & Nutt, D. J. Anhedonia revisited: is there a role for dopamine-targeting drugs for depression? J. Psychopharmacol. 27, 869–877 (2013).

    Article  PubMed  CAS  Google Scholar 

  133. 133.

    Di Giannantonio, M. & Martinotti, G. Anhedonia and major depression: the role of agomelatine. Eur. Neuropsychopharmacol. 22, S505–S510 (2012).

    Article  PubMed  CAS  Google Scholar 

  134. 134.

    Thobois, S. et al. Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil. Brain 136, 1568–1577 (2013).

    Article  PubMed  Google Scholar 

  135. 135.

    Devos, D. et al. Rivastigmine in apathetic but dementia and depression-free patients with Parkinson’s disease: a double-blind, placebo-controlled, randomised clinical trial. J. Neurol. Neurosurg. Psychiatry 85, 668–674 (2014).

    Article  PubMed  Google Scholar 

  136. 136.

    McGirr, A. et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol. Med. 45, 693–704 (2015).

    Article  PubMed  CAS  Google Scholar 

  137. 137.

    Kokkinou, M., Ashok, A. H. & Howes, O. D. The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders. Mol. Psychiatry 23, 59–69 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. 138.

    Lally, N. et al. Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl Psychiatry 4, e469 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. 139.

    Peciña, M. et al. Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: implications for anhedonia, anxiety and treatment response. Eur. Neuropsychopharmacol. 27, 977–986 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  140. 140.

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

    Article  PubMed  Google Scholar 

  141. 141.

    Sarchiapone, M. et al. Dopamine transporter binding in depressed patients with anhedonia. Psychiatry Res. 147, 243–248 (2006).

    Article  PubMed  CAS  Google Scholar 

  142. 142.

    Bloomfield, M. A. P., Morgan, C. J. A., Kapur, S., Curran, H. V. & Howes, O. D. The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study. Psychopharmacology 231, 2251–2259 (2014).

    Article  PubMed  CAS  Google Scholar 

  143. 143.

    Felger, J. C. & Treadway, M. T. Inflammation effects on motivation and motor activity: role of dopamine. Neuropsychopharmacology 42, 216–241 (2017). This paper presents a clear account of the links between the immune and DA systems, including how inflammation may result in a decrease in DA transmission, leading to symptoms related to amotivation.

    Article  PubMed  CAS  Google Scholar 

  144. 144.

    Felger, J. C. & Miller, A. H. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Front. Neuroendocrinol. 33, 315–327 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. 145.

    Kapur, S. & Remington, G. Serotonin–dopamine interaction and its relevance to schizophrenia. Am. J. Psychiatry 153, 466–476 (1996).

    Article  PubMed  CAS  Google Scholar 

  146. 146.

    Bailey, M. R. et al. The effects of pharmacological modulation of the serotonin 2C receptor on goal-directed behavior in mice. Psychopharmacology 233, 615–624 (2016).

    Article  PubMed  CAS  Google Scholar 

  147. 147.

    Deakin, J. F. W. & Graeff, F. G. 5-HT and mechanisms of defence. J. Psychopharmacol. 5, 305–315 (1991).

    Article  PubMed  CAS  Google Scholar 

  148. 148.

    Maier, S. F. & Watkins, L. R. Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci. Biobehav. Rev. 29, 829–841 (2005).

    Article  PubMed  CAS  Google Scholar 

  149. 149.

    Daw, N. D., Kakade, S. & Dayan, P. Opponent interactions between serotonin and dopamine. Neural Netw. 15, 603–616 (2002).

    Article  PubMed  Google Scholar 

  150. 150.

    Boureau, Y.-L. & Dayan, P. Opponency revisited: competition and cooperation between dopamine and serotonin. Neuropsychopharmacology 36, 74–97 (2011).

    Article  PubMed  CAS  Google Scholar 

  151. 151.

    Kranz, G. S., Kasper, S. & Lanzenberger, R. Reward and the serotonergic system. Neuroscience 166, 1023–1035 (2010).

    Article  PubMed  CAS  Google Scholar 

  152. 152.

    Nakamura, K., Matsumoto, M. & Hikosaka, O. Reward-dependent modulation of neuronal activity in the primate dorsal raphe nucleus. J. Neurosci. 28, 5331–5343 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. 153.

    Fonseca, M. S., Murakami, M. & Mainen, Z. F. Activation of dorsal raphe serotonergic neurons promotes waiting but is not reinforcing. Curr. Biol. 25, 306–315 (2015).

    Article  PubMed  CAS  Google Scholar 

  154. 154.

    Luo, M., Zhou, J. & Liu, Z. Reward processing by the dorsal raphe nucleus: 5-HT and beyond. Learn. Mem. 22, 452–460 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. 155.

    Faulkner, P. & Deakin, J. F. W. The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion. Neurosci. Biobehav. Rev. 46, 365–378 (2014).

    Article  PubMed  CAS  Google Scholar 

  156. 156.

    Macoveanu, J. Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies. Brain Res. 1556, 19–27 (2014).

    Article  PubMed  CAS  Google Scholar 

  157. 157.

    Seymour, B., Daw, N. D., Roiser, J. P., Dayan, P. & Dolan, R. Serotonin selectively modulates reward value in human decision-making. J. Neurosci. 32, 5833–5842 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. 158.

    Cools, R. et al. Tryptophan depletion disrupts the motivational guidance of goal-directed behavior as a function of trait impulsivity. Neuropsychopharmacology 30, 1362–1373 (2005).

    Article  PubMed  CAS  Google Scholar 

  159. 159.

    Maillet, A. et al. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson’s disease. Brain 139, 2486–2502 (2016).

    Article  PubMed  Google Scholar 

  160. 160.

    Da Silva, S. et al. Investigating consummatory and anticipatory pleasure across motivation deficits in schizophrenia and healthy controls. Psychiatry Res. 254, 112–117 (2017).

    Article  PubMed  Google Scholar 

  161. 161.

    Richards, D. A. et al. Cost and outcome of behavioural activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial. Lancet 388, 871–880 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  162. 162.

    Lutgens, D., Gariepy, G. & Malla, A. Psychological and psychosocial interventions for negative symptoms in psychosis: systematic review and meta-analysis. Br. J. Psychiatry 210, 324–332 (2017).

    Article  PubMed  Google Scholar 

  163. 163.

    Rizvi, S. J., Pizzagalli, D. A., Sproule, B. A. & Kennedy, S. H. Assessing anhedonia in depression: potentials and pitfalls. Neurosci. Biobehav. Rev. 65, 21–35 (2016). This is a thorough review of questionnaire, interview and behavioural measurements commonly used to assess anhedonia in humans and behavioural tests assessing related constructs in animals.

    Article  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Strauss, G. P. & Gold, J. M. A. Psychometric comparison of the clinical assessment interview for negative symptoms and the brief negative symptom scale. Schizophr. Bull. 42, 1384–1394 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  165. 165.

    Kaji, Y. & Hirata, K. Apathy and anhedonia in Parkinson’s disease. ISRN Neurol. 2011, 219427 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  166. 166.

    Haarasilta, L., Marttunen, M., Kaprio, J. & Aro, H. The 12-month prevalence and characteristics of major depressive episode in a representative nationwide sample of adolescents and young adults. Psychol. Med. 31, 1169–1179 (2001).

    Article  PubMed  CAS  Google Scholar 

  167. 167.

    Keller, M. B. et al. Results of the DSM-IV mood disorders field trial. Am. J. Psychiatry 152, 843–849 (1995).

  168. 168.

    Kiwanuka, J. N., Strauss, G. P., McMahon, R. P. & Gold, J. M. Psychological predictors of functional outcome in people with schizophrenia. Schizophr. Res. 157, 299–304 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Daw, N. D. Decision Making, Affect, and Learning (eds Delgado, M. R., Phelps, E. A. & Robbins, T. W.) 3–38 (Oxford Univ. Press, Oxford, 2011).

  170. 170.

    Anticevic, A. & Murray, J. D. (eds) Computational Psychiatry: Mathematical Modeling of Mental Illness. (Academic Press, Elsevier, London, 2017).

    Google Scholar 

  171. 171.

    Gelman, A. & Shalizi, C. R. Philosophy and the practice of Bayesian statistics. Br. J. Math. Stat. Psychol. 66, 8–38 (2013).

    Article  PubMed  Google Scholar 

  172. 172.

    Pessiglione, M., Seymour, B., Flandin, G., Dolan, R. J. & Frith, C. D. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature 442, 1042–1045 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. 173.

    Sutton, R. S. & Barto, A. G. Reinforcement Learning: An Introduction (MIT Press, Cambridge, 1998).

    Google Scholar 

  174. 174.

    Assadi, S. M., Yücel, M. & Pantelis, C. Dopamine modulates neural networks involved in effort-based decision-making. Neurosci. Biobehav. Rev. 33, 383–393 (2009).

    Article  PubMed  CAS  Google Scholar 

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M.H. and J.P.R. are supported by awards from the Wellcome Trust. M.H. is also supported by the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Wellcome Trust Centre for Integrative Neuroimaging, Oxford. J.P.R. is also supported by the Leverhulme Trust.

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Nature Reviews Neuroscience thanks J. Salamone and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Both authors researched data for the article, made substantial contributions to discussion of the content, wrote the manuscript and reviewed or edited the manuscript before submission.

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Correspondence to Masud Husain.

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Competing interests

M.H. has received an honorarium from Eli Lilly for speaking at their UK annual research symposium in 2017. J.P.R. is a consultant for Cambridge Cognition Ltd, Takeda and GE.

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A reason or reasons for acting or behaving in a particular way.

Negative symptoms

Thoughts, feelings or behaviours normally present that are absent or diminished.

DSM-IV field trials

Reports on the first attempts to apply the diagnostic criteria laid down in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition in real-world settings.


Inability to perform self-directed, purposeful activities.


Reduced spontaneous verbal, motor, cognitive and emotional behaviours.

Akinetic mutism

Loss of ability to self-initiate limb movement and speech.


Loss of energy.


Weariness or diminished ability following mental or physical activity.


Approach or goal-seeking phase of behaviour.


Completion or consummation phase of behaviour.


Acquisition of information, in this case to alter future behaviour.


The number of examples generated of a verbal category (for example, words beginning with the letter F) or a non-verbal category (for instance, different patterns on a dot array using four straight lines).

Pavlovian–instrumental transfer

(PIT). The influence of an irrelevant conditioned stimulus on ongoing instrumental behaviour.

Iowa Gambling task

A neuropsychological test of decision making for reward.

Reward responsiveness

The development of a bias towards a more frequently rewarded stimulus.


When a model becomes too complex (has too many parameters) and begins to describe random error in the data rather than the relationships between variables.

Inverse temperature parameter

A constant in the softmax decision rule. It affects the steepness of the function around the inflexion point, resulting in more consistent choices at higher values.

Incremental learning

Learning over trials.

Reward-prediction error

A computational quantity indicating the difference between expected and actual outcomes.

Primary reward

Rewarding stimuli that facilitate survival of an organism or its offspring, such as food, water and sex.

Behavioural activation therapy

A psychological therapy that focuses on activity scheduling to encourage patients to approach activities that they avoid and on analysing processes (for example, rumination) that serve as forms of avoidance.

Cognitive behavioural therapy

A psychological therapy that aims to assist a person to change their thinking and behaviour by practising effective strategies to decrease symptoms and distress.

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Husain, M., Roiser, J.P. Neuroscience of apathy and anhedonia: a transdiagnostic approach. Nat Rev Neurosci 19, 470–484 (2018).

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