The Dorsolateral Prefrontal Cortex, the Apathetic Syndrome, and Free Will

  • Domenico ChirchigliaEmail author
  • Pasquale Chirchiglia
  • Rosa Marotta
  • Dorotea Pugliese
  • Giusy Guzzi
  • Serena Lavano


The prefrontal cortex is deputed to higher functions, such as behavior and personality. It includes three regions: ventromedial, orbitofrontal, and dorsolateral. Each of them has a function. Devising, programming, and planning are all conditions related to the dorsolateral cortex, also responsible for rational content and decision. Damage to this region results in apathetic syndrome, a condition that causes loss of interest, initiative, and attention, and in the most severe cases leads to a lethargic state. It is also known as a form of secondary depression, the so-called pseudo-depression syndrome, according to Karl Kleist or apathetic-abulic-akinetic syndrome, according to Alexander Luria. The prefrontal dorsolateral syndrome is responsible for the reduction or abolition of free will. Free will is an expression of individual freedom. It allows the human being to have and express own opinions as well as to respect those of others. Free will is related to moral sense, a binomial which directs the individual towards a proper social conduct. In this review, we describe the effects of the pseudo-depression syndrome on free will, of which we treat both the anatomical site and the social aspect.


Frontal lobe Apathetic syndrome Free will Prefrontal cortex Dorsolateral syndrome 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. Berthoz, S., Grezes, J., Armony, J. L., Passingham, R. E., & Dolan, R. J. (2006). Affective response to one’s own moral violations. Neuroimage, 31, 945–950.CrossRefGoogle Scholar
  2. Blumer, D. (1970). Neurological states masquerading as psychoses. Maryland State Medical Journal, 19(10), 55–60.Google Scholar
  3. Ciaramelli, E., Muccioli, M., Ladavas, E., & di Pellegrino, G. (2007). Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex. Social Cognitive and Affective Neuroscience, 2, 84–92.CrossRefGoogle Scholar
  4. D’Argembeau, A., Xue, G., Lu, Z. L., Van der Linden, M., & Bechara, A. (2008). Neural correlates of envisioning emotional events in the near and far future. Neuroimage, 40, 398–407.CrossRefGoogle Scholar
  5. Damasio, A. R. (1994). Descartes’ error: emotion, reason, and the human brain. New York: Putnam.Google Scholar
  6. Darby, R. R., Joutsa, J., Burke, M. J., & Fox, M. D. (2018). Lesion network localization of free will. Proceedings of the National Academy of Sciences of the United States of America, 115(42), 10792–10797. Scholar
  7. De Waal, F. B. (2005). How animals do business. Scientific American, 292, 54–61.Google Scholar
  8. Fasullo, S. (1971). The moriatic syndrome. Acta Neurol (Napoli)., 26(5), 614–632.Google Scholar
  9. Filevich, E., Vanneste, P., Brass, M., Fias, W., Haggard, P., & Kühn, S. (2013). Brain correlates of subjective freedom of choice. Consciousness and Cognition, 22(4), 1271–1284. Scholar
  10. Fiske, A. P. (2002). Moral emotions provide the self-control needed to sustain social relationships. Self and Identity, 1, 169–175.CrossRefGoogle Scholar
  11. Glozman, J. M. (2007). A.R. Luria and the history of Russian neuropsychology. Journal of the History of the Neurosciences, 16(1–2), 168–180.CrossRefGoogle Scholar
  12. Greene, J. D., Sommerville, R. B., Nystrom, L. E., Darley, J. M., & Cohen, J. D. (2001). An fMRI investigation of emotional engagement in moral judgment. Science., 293, 2105–2108.CrossRefGoogle Scholar
  13. Greene, J. D., Nystrom, L. E., Engell, A. D., Darley, J. M., & Cohen, J. D. (2004). The neural bases of cognitive conflict and control in moral judgment. Neuron, 44, 389–400.CrossRefGoogle Scholar
  14. Haggard, P. (2008). Human volition: towards a neuroscience of will. Nature Reviews. Neuroscience, 9(12), 934–946. Scholar
  15. Haidt, J. (2001). The emotional dog and its rational tail: a social intuitionist approach to moral judgment. Psychological Review, 108, 814–834.CrossRefGoogle Scholar
  16. Haidt, J. (2007). The new synthesis in moral psychology. Science, 316, 998–1002.CrossRefGoogle Scholar
  17. Hallett, M. (2016). Physiology of free will. Annals of Neurology, 80(1), 5–12. Scholar
  18. Hause, M. D., Cushman, F. A., & Young, L. L. (2006). A dissociation between moral judgments and justifications. Minde Languag., 22, 1–21.Google Scholar
  19. Hauser, M. D. (2006). Moral minds: how nature designed our universal sense of right and wrong. New York: Ecco/Harper Collins.Google Scholar
  20. Heekeren, H. R., Wartenburger, I., Schmidt, H., Schwintowski, H. P., & Villringer, A. (2003). An fMRI study of simple ethical decision-making. Neuroreport, 14, 1215–1219.CrossRefGoogle Scholar
  21. Kleist, K. (1952). Brain and psyche. The Journal of Nervous and Mental Disease, 116(6), 776–782.CrossRefGoogle Scholar
  22. Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., & Damasio, A. (2007). Damage to the prefrontal cortex increases utilitarian moral judgments. Nature., 446, 908–911.CrossRefGoogle Scholar
  23. Lieberman, M. D. (2007). Social cognitive neuroscience: a review of core processes. Annual Review of Psychology, 58, 259–289.CrossRefGoogle Scholar
  24. Moise, D., & Madhusoodanan, S. (2006). Psychiatric symptoms associated with brain tumors: a clinical enigma. CNS Spectrums, 11, 28–31.CrossRefGoogle Scholar
  25. Moll, J., & Schulkin, J. (2009). Social attachment and aversion in human moral cognition. Neuroscience and Biobehavioral Reviews, 33, 456–465.CrossRefGoogle Scholar
  26. Moll, J., Oliveira-Souza, R., Eslinger, P. J., et al. (2002). The neural correlates of moral sensitivity: a functional magnetic resonance imaging investigation of basic and moral emotions. The Journal of Neuroscience, 22, 2730–2736.CrossRefGoogle Scholar
  27. Moll, J., de Oliveira-Souza, R., & Eslinger, P. J. (2003). Morals and the human brain: a working model. Neuroreport, 14, 299–305.CrossRefGoogle Scholar
  28. Monroe AE, Dillon KD, Malle BF. Bringing free will down to Earth: people’s psychological concept of free will and its role in moral judgment. Consciousness and Cognition 2014;27:100–108. Epub 2014 May 20.
  29. Neumärker, K. J., & Bartsch, A. J. (2003). Karl Kleist (1879–1960)—a pioneer of neuropsychiatry. Hist Psychiatry, 14(56 Pt 4), 411–458.CrossRefGoogle Scholar
  30. Oreskovic, N. M., Strother, C. G., & Zibners, L. M. (2007). An unusual case of a central nervous system tumor presenting as a chief complaint of depression. Pediatric Emergency Care, 23, 486–488.CrossRefGoogle Scholar
  31. Ozdilek, B., & Midi, L. (2011). Brain tumor presenting with psychiatric symptoms. Journal of Neuropsychiatry and Clinical Neurosciences, 23, E43–E44.CrossRefGoogle Scholar
  32. Queralt, M., Alegre, J., Suriñach, J. M., & de Sevilla, F. (1993). Frontal tumor and mental deterioration. Revista Clínica Española, 193(4), 185–186.Google Scholar
  33. Rothbart, M. K., & Derryberry, D. (1981). Development of individual differences in temperament. In M. E. Lamb & A. Brown (Eds.), Advances in developmental psychology, Vol. 1 (pp. 37–86). Hillsdale: Erlbaum.Google Scholar
  34. Rothbart, M. K., & Posner, M. I. (1985). Temperament and the development of self-regulation. In L. H. Hartlage & C. F. Telzrow (Eds.), Neuropsychology of individual differences: a developmental perspective (pp. 93–124). New York: Plenum.CrossRefGoogle Scholar
  35. Rothbart, M. K., Ziaie, H., & O’Boyle, C. G. (1992). Self-regulation and emotion in infancy. New Directions for Child Development, (55), 7–23.Google Scholar
  36. Schaich Borg, J., Hynes, C., Van Horn, J., Grafton, S., & Sinnott-Armstrong, W. (2006). Consequences, action, and intention as factors in moral judgments: an FMRI investigation. Journal of Cognitive Neuroscience, 18, 803–817.CrossRefGoogle Scholar
  37. Signorelli, F., Ruggeri, F., Iofrida, G., Isnard, J., Chirchiglia, D., Lavano, A., Volpentesta, G., Signorelli, C. D., & Guyotat, J. S. (2007). Indications and limits of intraoperative cortico-subcortical mapping in brain tumor, surgery: an analisys of 101 consecutive cases. Journal of Neurosurgical Sciences, 51(3), 113–127.Google Scholar
  38. Signorelli F., Chirchiglia D., Maduri R. . Surgical resections of tumor infiltrating left insula and perisylvian opercula-utility of anatomic landmarks implemented by intraoperative functional brain mapping, Intech 2013.Google Scholar
  39. Tangney, J. P., Stuewig, J., & Mashek, D. J. (2007). Mirror neuron system: basic findings and clinical applications. Annals of Neurology, 62, 213–218.CrossRefGoogle Scholar
  40. Vohs, K. D., & Schooler, J. W. (2008). The value of believing in free will: encouraging a belief in determinism increases cheating. Psychological Science, 19(1), 49–54. CrossRefGoogle Scholar
  41. Wilson, J. Q. (1995). The moral sense. New York: Simon & Schuster.Google Scholar

Copyright information

© Neuroscientia 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversity of CatanzaroCatanzaroItaly

Personalised recommendations