Ventromedial prefrontal cortex
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|Brain: Ventromedial prefrontal cortex|
Ventromedial prefrontal cortex shown on medial and ventral views of the brain, reflecting approximate location of damage in patients with decision making deficits.
Medial surface of the brain with Brodmann's areas numbered.
|Latin||Cortex praefrontalis ventromedialis|
The ventromedial prefrontal cortex (vmPFC) is a part of the prefrontal cortex in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe at the bottom of the cerebral hemispheres and is implicated in the processing of risk and fear. It also plays a role in the inhibition of emotional responses, and in the process of decision making.
The ventromedial prefrontal cortex has been described as equivalent to Brodmann area 10. However, not all sources agree on the boundaries of the area. Different researchers use the term ventromedial prefrontal cortex differently. Sometimes, the term is saved for the area above the medial orbitofrontal cortex, while at other times, 'ventromedial prefrontal cortex' is used to describe a broad area in the lower (ventral) central (medial) region of the prefrontal cortex, of which the medial orbitofrontal cortex constitutes the lowermost part. This latter, broader area, corresponds to the area damaged in patients with decision-making impairments investigated by António Damásio and colleagues (see diagram, and below).
To get a rough idea of where the ventromedial prefrontal cortex is, recall that the left and right hemispheres of the brain are separated [by the longitudinal cerebral fissure]. Now imagine you could take your hand and starting at the anterior brain (where your forehead is) insert it into this gap until you reached the insula (a structure that is beneath the frontal lobe). Your palm would be touching a part of the prefrontal cortex, which is in the front part of the brain and the lower part of your palm would be touching the ventral medial prefrontal cortex.
The ventromedial prefrontal cortex is connected to and receives input from the ventral tegmental area, amygdala, the temporal lobe, the olfactory system, and the dorsomedial thalamus. It, in turn, sends signals to many different brain regions including; The temporal lobe, amygdala, the lateral hypothalamus, the hippocampal formation, the cingulate cortex, and certain other regions of the prefrontal cortex. This huge network of connections affords the vmPFC the ability to receive and monitor large amounts of sensory data and to affect and influence a plethora of other brain regions, particularly the amygdala.
Functional differences between the orbitofrontal and ventromedial areas of the pre-frontal cortex have not yet been clearly established, although the areas of the ventromedial cortex superior to the orbitofrontal cortex are much less associated with social functions and more with pure emotion regulation. Research in developmental neuroscience also suggested that neural networks in the ventromedial prefrontal cortex are rapidly developing during adolescence and young adulthood supporting emotion regulation through the amygdala, being associated with a decrease in cortisol levels.
There are only a few reports of people with early-onset vmPFC (for instance, during childhood), but these individuals tend to have severe antisocial behavior and impaired moral judgment. Compared to individuals with damage later in life, their behavior pattern is similar but more severe.
Patients with bilateral lesions of the vmPFC develop severe impairments in personal and social decision-making even though most of their intellectual ability is preserved. For instance, they have difficulties in choosing between options with uncertain outcomes, whether the uncertainty is in the form of a risk or of an ambiguity. After their lesion, these patients have an impaired capacity to learn from their mistakes, making the same decisions again and again even though they lead to negative consequences. These patients choose alternatives that give immediate rewards, but seem to be blind to the future consequences of their actions. However, the underlying mechanisms of this behaviour are not yet fully understood.
People with damage to the ventromedial prefrontal cortex still retain the ability to consciously make moral judgments without error, but only in hypothetical situations presented to them. There is a gap in reasoning when applying the same moral principles to similar situations in their own lives. The result is that people make decisions that are inconsistent with their self professed moral values.
Regulation of emotion
Activation of the vmPFC is associated with successful suppression of emotional responses to a negative emotional signal. Patients with vmPFC lesions show defects both in emotional response and emotion regulation. Their emotional responsivity is generally diminished and they show markedly reduced social emotions such as compassion, shame and guilt. These are emotions that are closely associated with moral values. Patients also exhibit poorly regulated anger and frustration tolerance in certain circumstances.
Patients with focal lesions in the vmPFC show personality changes such as lack of empathy, irresponsibility, and poor decision making. These traits are similar to psychopathic personality traits.
The right half of the ventromedial prefrontal cortex was associated with regulating the interaction of cognition and affect in the production of empathic responses. Hedonic (pleasure) responses were also associations to orbitofrontal cortex activity level by Morten Kringelbach. This finding contributes findings suggesting ventromedial prefrontal cortex being associated with preference judgement, possibly assigning the ventromedial prefrontal cortex a key role in constructing one's self. Studies with PTSD also supported the idea that the ventromedial prefrontal cortex is an important component for reactivating past emotional associations and events, therefore essentially mediating pathogenesis of PTSD. Treatments geared to the activation of the ventromedial prefrontal cortex were therefore suggested for PTSD. The right half of the ventrolateral prefrontal cortex, being active during emotion regulation, was activated when participants were offered an unfair offer in a scenario. Specific deficits in reversal learning and decision-making have led to the hypothesis that the ventromedial prefrontal cortex is a major locus of dysfunction in the mild stages of the behavioural variant of frontotemporal dementia.
Somatic marker hypothesis
One particularly notable theory of vmPFC function is the somatic marker hypothesis, accredited to António Damásio. By this hypothesis, the vmPFC has a central role in adapting somatic markers—emotional associations, or associations between mental objects and visceral (bodily) feedback—for use in natural decision making. This account also gives the vmPFC a role in moderating emotions and emotional reactions because whether the vmPFC decides the markers are positive or negative affects the appropriate response in a particular situation. However, a critical review of this hypothesis concluded that there is a need for additional empirical data to support the somatic marker theory.
Another role that the vmPFC plays is in the process of extinction, the gradual weakening and eventual cessation of a conditioned response. The specific role played by the vmPFC concerning extinction is not well understood, but it is believed that it plays a necessary role in the recall of extinction learning after a long period of time. Studies show that it aids in the consolidation of extinction learning. A separate study has implicated the correlation between the cortical thickness of the vmPFC and the degree of extinction memory. Patients with larger vmPFCs tended to have lower responses to the extinct conditioned stimulus, therefore suggesting a superior extinction memory. 
Ventromedial prefrontal cortex lesions were also associated with a deficit in processing gender specific social cues. One experiment tested the ability of patients with vmPFC lesions to categorize gender-specific names, attributes, and attitudes compared to patients with dorsolateral prefrontal cortex lesions and control subjects. Whereas the patients with dorsolateral prefrontal cortex lesions performed similarly to the control subjects on tests indicating gender stereotypes, patients with ventromedial prefrontal cortex lesions demonstrated impaired stereotypic social knowledge. 
- Bechara A, Damasio H, Tranel D, Anderson SW (January 1998). "Dissociation Of working memory from decision making within the human prefrontal cortex". J. Neurosci. 18 (1): 428–37. PMID 9412519.
- Finger, E. C.; Marsh, A. A.; Mitchell, D. G.; Reid, M. E.; Sims, C.; Budhani, S.; Kosson, D. S.; Chen, G.; Towbin, K. E.; Leibenluft, E.; Pine, D. S.; Blair, J. R. (2008). "Abnormal Ventromedial Prefrontal Cortex Function in Children with Psychopathic Traits During Reversal Learning". Archives of General Psychiatry 65 (5): 586–594. doi:10.1001/archpsyc.65.5.586. PMC 3104600. PMID 18458210.
- Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print.
- Decety, J; Michalska, K (2010). "Neurodevelopmental changes in the circuits underlying empathy and sympathy from childhood to adulthood". Developmental Science 13 (1): 886–899. doi:10.1111/j.1467-7687.2009.00940.x. PMID 20977559.
- Aaron D Boes et al (2011). "Behavioral effects of congenital ventromedial prefrontal cortex malformation". BMC Neurology 11 (151). doi:10.1186/1471-2377-11-151.
- Bechara A, Tranel D, Damasio H (November 2000). Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain 123 (Pt 11): 2189–202. doi:10.1093/brain/123.11.2189. PMID 11050020.
- Michael Koenigs et al. "Damage to the prefrontal cortex increases utilitarian moral judgements". Nature (letter). doi:10.1038/nature05631.
- Fellows, L. K., and M. J. Farah. "The Role of Ventromedial Prefrontal Cortex in Decision Making: Judgment under Uncertainty or Judgment Per Se?" Cerebral Cortex 17.11 (2007): 2669-674. Print.
- Alexander Hänsel and Roland von Känel (2008). "The ventro-medial prefrontal cortex: a major link between the autonomic nervous system, regulation of emotion, and stress reactivity?". BioPsychoSocial Medicine 2 (21). doi:10.1186/1751-0759-2-21.
- Motzkin, Julian C.; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael (November 2011). "Reduced prefrontal connectivity in psychopathy". The Journal of Neuroscience 31 (48): 17348-48. doi: http://www.jneurosci.org/content/31/48/17348.long
- Quirk, Gregory J., Gregory K. Russo, Jill L. Barron, and Kelimer Lebron. "The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear." The Journal of Neuroscience 20.16 (2000): 6225-231. Print.
- Milad Mohammed R.; Quinn, Brian T.; Pitman, Roger K.; Orr, Scott P.; Fischl, Bruce; Rauch, Scott L. (July 2005). "Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory". Proc. Natl. Acad. Sci. U.S.A. 102 (30): 10706-30. doi: http://www.pnas.org/content/102/30/10706.full. These results are a possible factor for explaining why different people show different degrees of controlling their fear.
- Milne, Elizabeth; Grafman, Jordan (2001). "Ventromedial prefrontal cortex lesions in humans eliminate implicit gender stereotyping". The Journal of Neuroscience 21 (12): RC150.
- The Brain from Top to Bottom: Brain Abnormalities Associated With Anxiety Disorders
- Bechara A, Tranel D, Damasio H (November 2000). "Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions". Brain 123 (Pt 11): 2189–202. doi:10.1093/brain/123.11.2189. PMID 11050020.
- Quirk GJ, Russo GK, Barron JL, Lebron K (August 2000). "The role of ventromedial prefrontal cortex in the recovery of extinguished fear". J. Neurosci. 20 (16): 6225–31. PMID 10934272.
- "Scientists Draw Link Between Morality And Brain's Wiring". Wall Street Journal. 2007-05-11.
- Carey, Benedict (2007-03-22). "Brain Injury Said to Affect Moral Choices". New York Times.
- Shamay-Tsoory, S. G.; Tomer, R.; Berger, B. D.; Aharon-Peretz, J. (2003). "Characterization of Empathy Deficits following Prefrontal Brain Damage: The Role of the Right Ventromedial Prefrontal Cortex". Journal of Cognitive Neuroscience 15 (3): 324–37. doi:10.1162/089892903321593063. PMID 12729486.
- Hooper CJ, Luciana M, Conklin HM, Yarger RS (November 2004). "Adolescents' performance on the Iowa Gambling Task: implications for the development of decision making and ventromedial prefrontal cortex". Dev Psychol 40 (6): 1148–58. doi:10.1037/0012-16184.108.40.2068. PMID 15535763.
- Elliott R, Rees G, Dolan RJ (April 1999). "Ventromedial prefrontal cortex mediates guessing". Neuropsychologia 37 (4): 403–11. doi:10.1016/S0028-3932(98)00107-9. PMID 10215087.
- Rahman, S.; Sahakian, B.J.; Hodges, J.R.; Rogers, R.D.; Robbins, T.W. (1999). "Specific cognitive deficits in mild frontal variant frontotemporal dementia". Brain 122 (8): 1469–93. doi:10.1093/brain/122.8.1469.
- Jacques Mehler; Susana Franck (1995). Cognition on cognition. MIT Press. pp. 3–. ISBN 978-0-262-63167-9. "Intensity to Future Consequences Following Damage to Human Prefrontal Cortex"
- Urry HL, van Reekum CM, Johnstone T, et al. (April 2006). "Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults". J. Neurosci. 26 (16): 4415–25. doi:10.1523/JNEUROSCI.3215-05.2006. PMID 16624961.
- Paulus MP, Frank LR (July 2003). "Ventromedial prefrontal cortex activation is critical for preference judgments". NeuroReport 14 (10): 1311–5. doi:10.1097/01.wnr.0000078543.07662.02. PMID 12876463.
- Zald DH, Mattson DL, Pardo JV (February 2002). "Brain activity in ventromedial prefrontal cortex correlates with individual differences in negative affect". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 2450–4. doi:10.1073/pnas.042457199. PMC 122385. PMID 11842195.
- Tabibnia G, Satpute AB, Lieberman MD (April 2008). "The sunny side of fairness: preference for fairness activates reward circuitry (and disregarding unfairness activates self-control circuitry)". Psychol Sci 19 (4): 339–47. doi:10.1111/j.1467-9280.2008.02091.x. PMID 18399886.
- The Orbitofrontal Cortex: Linking Reward to Hedonic Experience
- Milne E, Grafman J (June 2001). "Ventromedial prefrontal cortex lesions in humans eliminate implicit gender stereotyping". J. Neurosci. 21 (12): RC150. PMID 11404442.
- Koenigs M, Huey ED, Raymont V, et al. (February 2008). "Focal brain damage protects against post-traumatic stress disorder in combat veterans". Nat. Neurosci. 11 (2): 232–7. doi:10.1038/nn2032. PMC 2693133. PMID 18157125.
- Sanchez-Navarro, Juan P.; Driscoll, David; Buchanan, Tony W.; Bechara, Antoine; Anderson, Steven W.; Tranel, Daniel (September 2011). "Ventromedial prefrontal cortex regulation of prepulse inhibition and emotional modulation of the startle reflex: effect of lesion onset". Front. Hum. Neurosci. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00165