Orbitofrontal cortex

The OFC is divided into multiple broad regions distinguished by cytoarchitecture, including Brodmann area 47/12, Brodmann area 11, Brodmann area 14, Brodmann area 13, and Brodmann area 10.{{cite book |last1=Mackey |first1=Sott |last2=Petrides |first2=Michael |editor1-last=Zald |editor1-first=David H. |editor2-last=Rauch |editor2-first=Scott |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |isbn=9780198565741 |page=34 |chapter=Chapter 2: The orbitofrontal cortex: sulcal and gyral morphology and architecture}} Four gyri are split by a complex of sulci that most frequently resembles a "H" or a "K" pattern. Extending along the rostro-caudal axis, two sulci, the lateral and orbital sulci, are usually connected by the transverse orbital sulcus, which extends along a medial-lateral axis. Most medially, the medial orbital gyrus is separated from the gyrus rectus by the olfactory sulcus.{{cite book |last1=Mackey |first1=Sott |last2=Petrides |first2=Michael |editor1-last=Zald |editor1-first=David H. |editor2-last=Rauch |editor2-first=Scott |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |isbn=9780198565741 |page=24 |chapter=Chapter 2: The orbitofrontal cortex: sulcal and gyral morphology and architecture}} Anteriorly, both the gyrus rectus and the medial part of the medial orbital gyrus consist of area 11(m), and posteriorly, area 14. The posterior orbital gyrus consists mostly of area 13, and is bordered medially and laterally by the anterior limbs of the medial and lateral orbital sulci. Area 11 makes up a large part of the OFC involving both the lateral parts of the medial orbital gyrus and the anterior orbital gyrus. The lateral orbital gyrus consists mostly of area 47/12. Most of the OFC is granular, although the caudal parts of area 13 and area 14 are agranular.{{cite book |last1=Passingham |first1=Richard E. |last2=Wise |first2=Steven P. |title=The Neurobiology of the Prefrontal Cortex: Anatomy, Evolution and Origin of Insight |date=1012 |publisher=Oxford University Press |location=Great Clarendon Street, Oxford |isbn=9780199552917 |page=97 |chapter=Chapter 4 Orbital prefrontal cortex: choosing objects based on outcomes}} These caudal regions, which sometimes include parts of the insular cortex, respond primarily to unprocessed sensory cues.{{cite journal |last1=Haber |first1=SN |last2=Behrens |first2=TE |title=The neural network underlying incentive-based learning: implications for interpreting circuit disruptions in psychiatric disorders. |journal=Neuron |date=3 September 2014 |volume=83 |issue=5 |pages=1019–39 |doi=10.1016/j.neuron.2014.08.031 |pmid=25189208 |pmc=4255982}}

The connectivity of the OFC varies somewhat along a rostral-caudal axis. The caudal OFC is more heavily interconnected with sensory regions, notably receiving direct input from the pyriform cortex. The caudal OFC is also the most heavily interconnected with the amygdala.{{cite book |last1=Barbas|first1=Helen|last2=Zikopoulos|first2=Basilis|editor1-last=Rauch |editor1-first=Scott L. |editor2-last=Zald |editor2-first=David H. |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |page=67|chapter=Chapter 4: Sequential and parallel circuits for emotional processing in the primate orbitofrontal cortex}} Rostrally, the OFC receives fewer direct sensory projections, and is less connected with the amygdala, but it is interconnected with the lateral prefrontal cortex and parahippocampus. The connectivity of the OFC has also been conceptualized as being composed of two networks; an orbital network composed of most of the central parts of the OFC, including most of the areas 47/12, 13, and 11; a medial network composed of the medial most and caudolateral regions of the OFC, as well as areas 24, 25 and 32 of the medial prefrontal cortex.{{cite book |last1=Price |first1=Joseph L. |editor1-last=Rauch |editor1-first=Scott L. |editor2-last=Zald |editor2-first=David H. |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |page=42 |chapter=Chapter 3: Connections of the orbital cortex}} The medial and orbital networks are sometimes referred to as the "visceromotor network" and the "sensory network", respectively.{{cite journal |last1=Rudebeck |first1=PH |last2=Murray |first2=EA |title=Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values. |journal=Annals of the New York Academy of Sciences |date=December 2011 |volume=1239 |issue=1 |pages=1–13 |doi=10.1111/j.1749-6632.2011.06267.x |pmid=22145870 |pmc=3951748|bibcode=2011NYASA1239....1R }}

The OFC receives projections from multiple sensory modalities. The primary olfactory cortex, gustatory cortex, secondary somatosensory cortex, superior and inferior temporal gyrus (conveying visual information) all project to the OFC.{{cite journal |last1=Rolls |first1=ET |title=The orbitofrontal cortex and reward. |journal=Cerebral Cortex |date=March 2000 |volume=10 |issue=3 |pages=284–94 |pmid=10731223|doi=10.1093/cercor/10.3.284 |doi-access=free }}{{cite journal |last1=Rolls |first1=ET |title=Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion. |journal=The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology |date=November 2004 |volume=281 |issue=1 |pages=1212–25 |doi=10.1002/ar.a.20126 |pmid=15470678|doi-access=free }} Evidence for auditory inputs is weak, although some neurons respond to auditory stimuli, indicating an indirect projection may exist. The OFC also receives input from the medial dorsal nucleus, insular cortex, entorhinal cortex, perirhinal cortex, hypothalamus, and amygdala.{{cite journal |last1=Rempel-Clower |first1=NL |title=Role of orbitofrontal cortex connections in emotion. |journal=Annals of the New York Academy of Sciences |date=December 2007 |volume=1121 |issue=1 |pages=72–86 |doi=10.1196/annals.1401.026 |pmid=17846152|bibcode=2007NYASA1121...72R |s2cid=21317263 }}

The orbitofrontal cortex is reciprocally connected with the perirhinal and entorhinal cortices, the amygdala, the hypothalamus, and parts of the medial temporal lobe. In addition to these outputs, the OFC also projects to the striatum, including the nucleus accumbens, caudate nucleus, and ventral putamen, as well as regions of the midbrain including the periaqueductal gray, and ventral tegmental area.{{cite book |last1=Price |first1=Joseph L. |editor1-last=Rauch |editor1-first=Scott L. |editor2-last=Zald |editor2-first=David H. |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |page=45 |chapter=Chapter 3: Connections of the orbital cortex}} OFC inputs to the amygdala synapse on multiple targets, including two robust pathways to the basolateral amygdala and intercalated cells of the amygdala, as well as a weaker direct projection to the central nucleus of the amygdala.

Multiple functions have been ascribed to the OFC, including mediating context-specific responses,{{cite journal|last1=Wikenheiser|first1=AM|last2=Schoenbaum|first2=G|title=Over the river, through the woods: cognitive maps in the hippocampus and orbitofrontal cortex.|journal=Nature Reviews. Neuroscience|date=August 2016|volume=17|issue=8|pages=513–23|doi=10.1038/nrn.2016.56|pmid=27256552|pmc=5541258}} encoding contingencies in a flexible manner, encoding value, encoding inferred value, inhibiting responses, learning changes in contingency, emotional appraisal,{{cite journal|last1=Fettes|first1=P|last2=Schulze|first2=L|last3=Downar|first3=J|title=Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness.|journal=Frontiers in Systems Neuroscience|date=2017|volume=11|pages=25|doi=10.3389/fnsys.2017.00025|pmid=28496402|pmc=5406748|doi-access=free}} altering behavior through somatic markers, driving social behavior, and representing state spaces.{{Cite journal|last1=Wilson|first1=Robert C.|last2=Takahashi|first2=Yuji K.|last3=Schoenbaum|first3=Geoffrey|last4=Niv|first4=Yael|date=January 2014|title=Orbitofrontal Cortex as a Cognitive Map of Task Space|journal=Neuron|volume=81|issue=2|pages=267–279|doi=10.1016/j.neuron.2013.11.005|pmid=24462094|pmc=4001869|issn=0896-6273}}{{cite journal|last1=Sadacca|first1=BF|last2=Wikenheiser|first2=AM|last3=Schoenbaum|first3=G|title=Toward a theoretical role for tonic norepinephrine in the orbitofrontal cortex in facilitating flexible learning.|journal=Neuroscience|date=14 March 2017|volume=345|pages=124–129|doi=10.1016/j.neuroscience.2016.04.017|pmid=27102419|pmc=5461826}}

While most of these theories explain certain aspects of electrophysiological observations and lesion related changes in behavior, they often fail to explain, or are contradicted by other findings.

One proposal that explains the variety of OFC functions is that the OFC encodes state spaces, or the discrete configuration of internal and external characteristics associated with a situation and its contingencies.{{cite journal|last1=Stalnaker|first1=TA|last2=Cooch|first2=NK|last3=Schoenbaum|first3=G|title=What the orbitofrontal cortex does not do.|journal=Nature Neuroscience|date=May 2015|volume=18|issue=5|pages=620–7|doi=10.1038/nn.3982|pmid=25919962|pmc=5541252}} For example, the proposal that the OFC encodes economic value may be a reflection of the OFC encoding task state value. The representation of task states could also explain the proposal that the OFC acts as a flexible map of contingencies, as a switch in task state would enable the encoding of new contingencies in one state, with the preservation of old contingencies in a separate state, enabling switching contingencies when the old task state becomes relevant again. The representation of task states is supported by electrophysiological evidence demonstrating that the OFC responds to a diverse array of task features, and is capable of rapidly remapping during contingency shifts. The representation of task states may influence behavior through multiple potential mechanisms. For example, the OFC is necessary for ventral tegmental area (VTA) neurons to produce a dopaminergic reward prediction error, and the OFC may encode expectations for computation of RPEs in the VTA.

Specific functions have been ascribed to subregions of the OFC. The lateral OFC has been proposed to reflect potential choice value, enabling fictive (counterfactual) prediction errors to potentially mediate switching choices during reversal, extinction and devaluation.{{Cite journal|last1=Tobia|first1=M. J.|last2=Guo|first2=R.|last3=Schwarze|first3=U.|last4=Boehmer|first4=W.|last5=Gläscher|first5=J.|last6=Finckh|first6=B.|last7=Marschner|first7=A.|last8=Büchel|first8=C.|last9=Obermayer|first9=K.|last10=Sommer|first10=T.|date=2014-04-01|title=Neural systems for choice and valuation with counterfactual learning signals|journal=NeuroImage|volume=89|pages=57–69|doi=10.1016/j.neuroimage.2013.11.051|pmid=24321554|s2cid=35280557|issn=1053-8119}} Optogenetic activation of the lOFC enhances goal directed over habitual behavior, possibly reflecting increased sensitivity to potential choices and therefore increased switching. The mOFC, on the other hand, has been proposed to reflect relative subjective value. In rodents, a similar function has been ascribed to the mOFC, encoding action value in a graded fashion, while the lOFC has been proposed to encode specific sensory features of outcomes.{{cite journal|last1=Izquierdo|first1=A|title=Functional Heterogeneity within Rat Orbitofrontal Cortex in Reward Learning and Decision Making.|journal=The Journal of Neuroscience |date=1 November 2017|volume=37|issue=44|pages=10529–10540|doi=10.1523/JNEUROSCI.1678-17.2017|pmid=29093055|pmc=6596524}} The lOFC has also been proposed to encode stimulus outcome associations, which are then compared by value in the mOFC.{{cite journal|last1=Rudebeck|first1=PH|last2=Murray|first2=EA|title=Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values.|journal=Annals of the New York Academy of Sciences|date=December 2011|volume=1239|issue=1|pages=1–13|doi=10.1111/j.1749-6632.2011.06267.x|pmid=22145870|pmc=3951748|bibcode=2011NYASA1239....1R}} Meta analysis of neuroimaging studies in humans reveals that a medial-lateral valence gradient exists, with the medial OFC responding most often to reward, and the lateral OFC responding most often to punishment. A posterior-anterior abstractness gradient was also found, with the posterior OFC responding to more simple rewards, and the anterior OFC responding more to abstract rewards.{{cite journal|last1=Kringelbach|first1=ML|last2=Rolls|first2=ET|title=The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.|journal=Progress in Neurobiology|date=April 2004|volume=72|issue=5|pages=341–72|doi=10.1016/j.pneurobio.2004.03.006|pmid=15157726|s2cid=13624163}} Similar results were reported in a meta-analysis of studies on primary versus secondary rewards.{{cite journal |last1=Sescousse |first1=G |last2=Caldú |first2=X |last3=Segura |first3=B |last4=Dreher |first4=JC |title=Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. |journal=Neuroscience and Biobehavioral Reviews |date=May 2013 |volume=37 |issue=4 |pages=681–96 |doi=10.1016/j.neubiorev.2013.02.002 |pmid=23415703|hdl=2066/117487 |s2cid=8335094 |hdl-access=free }}

The OFC and basolateral amygdala (BLA) are highly interconnected, and their connectivity is necessary for devaluation tasks. Damage to either the BLA or the OFC before, but only the OFC after devaluation, impairs performance.{{cite journal|last1=Padoa-Schioppa|first1=C|last2=Conen|first2=KE|title=Orbitofrontal Cortex: A Neural Circuit for Economic Decisions.|journal=Neuron|date=15 November 2017|volume=96|issue=4|pages=736–754|doi=10.1016/j.neuron.2017.09.031|pmid=29144973|pmc=5726577}} While the BLA only responds to cues predicting salient outcomes in a graded fashion in accordance with value, the OFC responds to both value and the specific sensory attributes of cue-outcome associations. While OFC neurons that, early in learning, respond to outcome receipt normally transfer their response to the onset of cues that predict the outcome, damage to the BLA impairs this form of learning.{{cite journal|last1=Sharpe|first1=MJ|last2=Schoenbaum|first2=G|title=Back to basics: Making predictions in the orbitofrontal-amygdala circuit.|journal=Neurobiology of Learning and Memory|date=May 2016|volume=131|pages=201–6|doi=10.1016/j.nlm.2016.04.009|pmid=27112314|pmc=5541254}}

The posterior orbitofrontal cortex (pOFC) is connected to the amygdala via multiple paths that are capable of both upregulating and downregulating autonomic nervous system activity.{{cite journal|last1=Barbas|first1=H|title=Flow of information for emotions through temporal and orbitofrontal pathways.|journal=Journal of Anatomy|date=August 2007|volume=211|issue=2|pages=237–49|doi=10.1111/j.1469-7580.2007.00777.x|pmid=17635630|pmc=2375774|quote=The posterior orbitofrontal cortex targets dual systems in the amygdala which have opposite effects on central autonomic structures. Both pathways originate in posterior orbitofrontal cortex, but one targets heavily the inhibitory intercalated masses, whose activation can ultimately disinhibit central autonomic structures during emotional arousal.}} Tentative evidence suggests that the neuromodulator dopamine plays a role in mediating the balance between the inhibitory and excitatory pathways, with a high dopamine state driving autonomic activity.{{cite journal|last1=Zikopoulos|first1=B|last2=Höistad|first2=M|last3=John|first3=Y|last4=Barbas|first4=H|title=Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.|journal= The Journal of Neuroscience|date=17 May 2017|volume=37|issue=20|pages=5051–5064|doi=10.1523/JNEUROSCI.3940-16.2017|pmid=28411274|pmc=5444191|quote=The specific innervation of inhibitory systems in the amygdala found here, along with the differential impact that dopamine has on them, makes it possible to hypothesize how distinct autonomic states may be achieved. A strong pOFC influence on IM that activates DARPP-32+ and CB+ neurons may help modulate autonomic function by downregulating CeM and thereby facilitate social interactions in primates....On the other hand, in a panic condition, when survival is perceived to be threatened, dopamine levels markedly increase. DARPP-32+ neurons in IM may thus be primarily inhibited, rendering the pOFC pathway ineffective.}}

It has been suggested that the medial OFC is involved in making stimulus-reward associations and the reinforcement of behavior, while the lateral OFC is involved in stimulus-outcome associations and the evaluation and possibly reversal of behavior.{{cite journal |author1=Walton M. E. |author2=Behrens T. E. |author3=Buckley M. J. |author4=Rudebeck P. H. |author5=Rushworth M. F. | year = 2010 | title = Separable learning systems in the macaque brain and the role of orbitofrontal cortex in contingent learning | journal = Neuron | volume = 65 | issue = 6| pages = 927–939 | doi=10.1016/j.neuron.2010.02.027 | pmid=20346766 | pmc=3566584}} Activity in the lateral OFC is found, for example, when subjects encode new expectations about punishment and social reprisal.{{cite journal |author1=Campbell-Meiklejohn D. K. |author2=Kanai R. |author3=Bahrami B. |author4=Bach D. R. |author5=Dolan R. J. |author6=Roepstorff A. |author7=Frith C. D. | year = 2012 | title = Structure of orbitofrontal cortex predicts social influence | journal = Current Biology | volume = 22 | issue = 4| pages = R123–R124 | doi=10.1016/j.cub.2012.01.012|pmid=22361146 |pmc=3315000 |bibcode=2012CBio...22.R123C }}{{cite journal |author1=Tanferna A. |author2=López-Jiménez L. |author3=Blas J. |author4=Hiraldo F. |author5=Sergio F. | year = 2012 | title = How Expert Advice Influences Decision Making | journal = PLOS ONE | volume = 7 | issue = 11 | doi = 10.1371/journal.pone.0049748 |pmid=23185425 |pmc=3504100 | page=e49748|bibcode=2012PLoSO...749748M |doi-access=free }}

The mid-anterior OFC has been found to consistently track subjective pleasure in neuroimaging studies. A hedonic hotspot has been discovered in the anterior OFC, which is capable of enhancing liking response to sucrose. The OFC is also capable of biasing the affective responses induced by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonism in the nucleus accumbens towards appetitive responses.{{cite journal|last1=Berridge|first1=KC|last2=Kringelbach|first2=ML|title=Pleasure systems in the brain.|journal=Neuron|date=6 May 2015|volume=86|issue=3|pages=646–64|doi=10.1016/j.neuron.2015.02.018|pmid=25950633|pmc=4425246}}

The OFC is capable of modulating aggressive behavior via projections to interneurons in the amygdala that inhibit glutaminergic projections to the ventromedial hypothalamus.{{Cite book |last=Numan |first=Michael |url=https://www.worldcat.org/title/879584151 |title=Neurobiology of social behavior: toward an understanding of the prosocial and antisocial brain |date=2015 |publisher=Elsevier |isbn=978-0-12-416040-8 |location=London, UK; Waltham, MA |page=85 |oclc=879584151}}

Neurons in the OFC respond both to primary reinforcers, and to cues that predict rewards across multiple sensory domains. The evidence for responses to visual, gustatory, somatosensory, and olfactory stimuli is robust, but evidence for auditory responses is weaker. In a subset of OFC neurons, neural responses to rewards or reward cues are modulated by individual preference and by internal motivational states such as hunger. A fraction of neurons that respond to sensory cues predicting a reward are selective for reward, and exhibit reversal behavior when cue outcome relationships are swapped. Neurons in the OFC also exhibit responses to the absence of an expected reward and punishment. Another population of neurons exhibits responses to novel stimuli and can "remember" familiar stimuli for up to a day.{{cite book |last1=Rolls |first1=Edmund T. |editor1-last=Zald |editor1-first=David H. |editor2-last=Rauch |editor2-first=Scott L. |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |chapter=Chapter 5 The Neurophysiology and Functions of the Orbitofrontal Cortex}}

During cued reward or cued instrumental reward tasks, neurons in the OFC exhibit three general patterns of firing; firing in response to cues: firing before reward receipt; firing in response to reward receipt. In contrast to the medial prefrontal cortex and striatum, OFC neurons do not exhibit firing mediated by movement. Their reward-predictive responses are, however, shaped by attention: when shifting attention between two alternatives, the same OFC population will represent positively the value of a currently attended item, but negatively the value of the unattended item.{{cite journal|author1 =Hunt LT|author2=Malalasekera WMN|author3 =de Berker AO|author4=Miranda B|author5=Farmer S|author6=Behrens TEJ|author7=Kennerley SW|title=Triple dissociation of attention and decision computations across prefrontal cortex.|journal=Nature Neuroscience |date=26 September 2018|volume=21|issue=9|pages=1471–1481|doi=10.1038/s41593-018-0239-5|pmid=30258238|pmc=6331040}} The encoding of reward magnitude is also flexible, and takes into account the relative values of present rewards.{{cite book |last1=Schultz |first1=Wolfram |last2=Tremblay |first2=Leon |editor1-last=Zald |editor1-first=David H. |editor2-last=Rauch |editor2-first=Scott :L. |title=The Orbitofrontal Cortex |date=2006 |publisher=Oxford University Press |location=New York |chapter=Chapter 7: Involvement of primate orbitofrontal neurons in reward, uncertainty, and learning 173 Wolfram Schultz and Leon Tremblay}}

The human OFC is among the least-understood regions of the human brain. It has been proposed that the OFC is involved in sensory integration, in representing the affective value of reinforcers, and in decision-making and expectation. In particular, the OFC seems to be important in signaling the expected rewards/punishments of an action given the particular details of a situation.{{cite journal |vauthors=Schoenbaum G, Takahashi Y, Liu T, McDannald M |title= Does the orbitofrontal cortex signal value? |journal=Annals of the New York Academy of Sciences |volume=1239|issue= 1 |pages=87–99 |year=2011 |doi=10.1111/j.1749-6632.2011.06210.x|pmid= 22145878 |pmc= 3530400 |bibcode= 2011NYASA1239...87S }} In doing this, the brain is capable of comparing the expected reward/punishment with the actual delivery of reward/punishment, thus, making the OFC critical for adaptive learning. This is supported by research in humans, non-human primates, and rodents.

The orbitofrontal cortex has been implicated in borderline personality disorder,{{Cite journal |last1=Berlin |first1=Heather A. |last2=Rolls |first2=Edmund T. |last3=Iversen |first3=Susan D. |date=December 2005 |title=Borderline personality disorder, impulsivity, and the orbitofrontal cortex |url=https://pubmed.ncbi.nlm.nih.gov/16330602/ |journal=The American Journal of Psychiatry |volume=162 |issue=12 |pages=2360–2373 |doi=10.1176/appi.ajp.162.12.2360 |issn=0002-953X |pmid=16330602}} schizophrenia, major depressive disorder, bipolar disorder, obsessive-compulsive disorder, addiction, post-traumatic stress disorder, autism,{{Cite journal|last1=Ha|first1=Sungji|last2=Sohn|first2=In-Jung|last3=Kim|first3=Namwook|last4=Sim|first4=Hyeon Jeong|last5=Cheon|first5=Keun-Ah|date=December 2015|title=Characteristics of Brains in Autism Spectrum Disorder: Structure, Function and Connectivity across the Lifespan|journal=Experimental Neurobiology|volume=24|issue=4|pages=273–284|doi=10.5607/en.2015.24.4.273|issn=1226-2560|pmc=4688328|pmid=26713076}} and panic disorder. Although neuroimaging studies have provided evidence for dysfunction in a wide variety of psychiatric disorders, the enigmatic nature of the OFCs role in behavior complicates the understanding of its role in the pathophysiology of psychiatric disorders.{{cite journal|last1=Jackowski|first1=AP|last2=Araújo Filho|first2=GM|last3=Almeida|first3=AG|last4=Araújo|first4=CM|last5=Reis|first5=M|last6=Nery|first6=F|last7=Batista|first7=IR|last8=Silva|first8=I|last9=Lacerda|first9=AL|title=The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings.|journal=Revista Brasileira de Psiquiatria|date=June 2012|volume=34|issue=2|pages=207–12|pmid=22729418|doi=10.1590/S1516-44462012000200014|doi-access=free}} The function of the OFC is not known, but its anatomical connections with the ventral striatum, amygdala, hypothalamus, hippocampus, and periaqueductal grey support a role in mediating reward and fear related behaviors.{{cite journal|last1=Milad|first1=MR|last2=Rauch|first2=SL|title=The role of the orbitofrontal cortex in anxiety disorders.|journal=Annals of the New York Academy of Sciences|date=December 2007|volume=1121|issue=1|pages=546–61|doi=10.1196/annals.1401.006|pmid=17698998|bibcode=2007NYASA1121..546M|s2cid=34467365}}

Meta-analyses of neuroimaging studies in obsessive compulsive disorder (OCD) report hyperactivity in areas generally considered to be part of the orbitofrontal segment of the cortico-basal ganglia-thalamo-cortical loop, such as the caudate nucleus, thalamus and orbitofrontal cortex. OCD has been proposed to reflect a positive feedback loop due to mutual excitation of the OFC and subcortical structures.{{cite journal|last1=Nakao|first1=T|last2=Okada|first2=K|last3=Kanba|first3=S|title=Neurobiological model of obsessive-compulsive disorder: evidence from recent neuropsychological and neuroimaging findings.|journal=Psychiatry and Clinical Neurosciences|date=August 2014|volume=68|issue=8|pages=587–605|doi=10.1111/pcn.12195|pmid=24762196|s2cid=5528241|doi-access=free}} While the OFC is usually overactive during symptom provocation tasks, cognitive tasks usually elicit hypoactivity of the OFC;{{cite journal|last1=Fineberg|first1=NA|last2=Potenza|first2=MN|last3=Chamberlain|first3=SR|last4=Berlin|first4=HA|last5=Menzies|first5=L|last6=Bechara|first6=A|last7=Sahakian|first7=BJ|last8=Robbins|first8=TW|last9=Bullmore|first9=ET|last10=Hollander|first10=E|title=Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review.|journal=Neuropsychopharmacology|date=February 2010|volume=35|issue=3|pages=591–604|doi=10.1038/npp.2009.185|pmid=19940844|pmc=3055606}} This may reflect a distinction between emotional and non-emotional tasks, lateral and medial OFC,{{cite journal|last1=Milad|first1=MR|last2=Rauch|first2=SL|title=Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways.|journal=Trends in Cognitive Sciences|date=January 2012|volume=16|issue=1|pages=43–51|doi=10.1016/j.tics.2011.11.003|pmid=22138231|pmc=4955838}} or simply just inconsistent methodologies.{{Cite book |last1=Vaghi |first1=M. M |url=https://academic.oup.com/book/24387/chapter/187315142 |title= Obsessive-compulsive Disorder: Phenomenology, Pathophysiology, and Treatment Obsessive-compulsive Disorder: Phenomenology, Pathophysiology, and Treatment |last2=Robbins |first2=T. W |date=October 2017 |publisher=Oxford University Press |editor-last=Pittenger |editor-first=Christopher |volume=1 |pages=239–240 |language=en |chapter=Task-Based Functional Neuroimaging Studies of Obsessive-Compulsive Disorder: A Hypothesis-Driven Review |doi=10.1093/med/9780190228163.003.0022}}

Animal models and cell-specific manipulations in relation to drug-seeking behavior implicate dysfunction of the OFC in addiction.{{cite journal|last1=Schoenbaum|first1=G|last2=Chang|first2=CY|last3=Lucantonio|first3=F|last4=Takahashi|first4=YK|title=Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We Can Treat Addiction.|journal=Neuropsychopharmacology|date=December 2016|volume=41|issue=13|pages=2966–2976|doi=10.1038/npp.2016.147|pmid=27510424|pmc=5101562}} Substance use disorders are associated with a variety of deficits related to flexible goal-directed behavior and decision-making. These deficits overlap with symptoms related to OFC lesions, and are also associated with reduced orbitofrontal grey matter, resting state hypometabolism, and blunted OFC activity during tasks involving decision-making or goal-directed behavior. In contrast to resting state and decision-related activity, cues associated with drugs evoke robust OFC activity that correlates with craving.{{cite journal |last1=Koob |first1=GF |last2=Volkow |first2=ND |title=Neurocircuitry of addiction. |journal=Neuropsychopharmacology |date=January 2010 |volume=35 |issue=1 |pages=217–38 |doi=10.1038/npp.2009.110 |pmid=19710631 |pmc=2805560}} Rodent studies also demonstrate that lOFC to BLA projections are necessary for cue-induced reinstatement of self-administration. These findings are all congruent with the role that the OFC plays in encoding the outcomes associated with certain stimuli.{{cite journal |last1=Moorman |first1=DE |title=The role of the orbitofrontal cortex in alcohol use, abuse, and dependence. |journal=Progress in Neuro-psychopharmacology & Biological Psychiatry |volume=87 |issue=Pt A |pages=85–107 |date=2 February 2018 |doi=10.1016/j.pnpbp.2018.01.010 |pmid=29355587|pmc=6072631 }}{{cite journal |last1=Gowin |first1=JL |last2=Mackey |first2=S |last3=Paulus |first3=MP |title=Altered risk-related processing in substance users: imbalance of pain and gain. |journal=Drug and Alcohol Dependence |date=1 September 2013 |volume=132 |issue=1–2 |pages=13–21 |doi=10.1016/j.drugalcdep.2013.03.019 |pmid=23623507 |pmc=3748224 |quote=Individuals with SUDs show several processing abnormalities during risk-taking decision-making, which include altered valuation of options (VMPFC) and outcomes (OFC and striatum), poor estimation of uncertainty (ACC and insular cortex), diminished executive control (DLPFC), and an attenuated influence of emotional salience (amygdala), and reduced responsiveness to somatic markers (somatosensory cortex). These neural processing differences during risk-taking among individuals with SUDs have been linked to poorer behavioral performance on risk-taking tasks and a more extensive history of substance use}}{{cite journal |last1=Chase |first1=HW |last2=Eickhoff |first2=SB |last3=Laird |first3=AR |last4=Hogarth |first4=L |title=The neural basis of drug stimulus processing and craving: an activation likelihood estimation meta-analysis. |journal=Biological Psychiatry |date=15 October 2011 |volume=70 |issue=8 |pages=785–93 |doi=10.1016/j.biopsych.2011.05.025 |pmid=21757184 |quote=A medial region of the OFC showed greater activation by drug cues compared with control cues and was consistently activated in the nontreatment-seeking subgroup. There is substantial evidence that this region plays a role in appetitive behavior and decision making (86,87), in particular with regard to expectations of reward (88) predicted by conditioned stimuli (89–94), which can control instrumental action selectio|pmc=4827617 }} The progression towards compulsive substance abuse may reflect a shift between model-based decision-making, where an internal model of future outcomes guides decisions, to model free learning, where decisions are based on reinforcement history. Model-based learning involves the OFC and is flexible and goal-directed, while model-free learning is more rigid; as a shift to more model-free behavior due to dysfunction in the OFC, like that produced by drug misuse, could underlie drug-seeking habits.{{cite journal |last1=Lucantonio |first1=F |last2=Caprioli |first2=D |last3=Schoenbaum |first3=G |title=Transition from 'model-based' to 'model-free' behavioral control in addiction: Involvement of the orbitofrontal cortex and dorsolateral striatum. |journal=Neuropharmacology |date=January 2014 |volume=76 Pt B |pages=407–15 |doi=10.1016/j.neuropharm.2013.05.033 |pmid=23752095 |pmc=3809026}}

Conduct disorder is associated with both structural abnormalities and functional abnormalities during affective tasks.{{cite journal |last1=Rubia |first1=K |title="Cool" inferior frontostriatal dysfunction in attention-deficit/hyperactivity disorder versus "hot" ventromedial orbitofrontal-limbic dysfunction in conduct disorder: a review. |journal=Biological Psychiatry |date=15 June 2011 |volume=69 |issue=12 |pages=e69–87 |doi=10.1016/j.biopsych.2010.09.023 |pmid=21094938|s2cid=14987165 }} Abnormalities in OFC structure, activity, and functional connectivity have all been observed in association with aggression.{{cite journal |last1=Rosell |first1=DR |last2=Siever |first2=LJ |title=The neurobiology of aggression and violence. |journal=CNS Spectrums |date=June 2015 |volume=20 |issue=3 |pages=254–79 |doi=10.1017/S109285291500019X |pmid=25936249 |doi-access=free }}

Neuroimaging studies have found abnormalities in the OFC in MDD and bipolar disorder. Consistent with the medial/reward and lateral/punishment gradient found in neuroimaging studies, some neuroimaging studies have observed elevated lateral OFC activity in depression, as well as reduced interconnectivity of the medial OFC, and enhanced interconnectivity in the lateral OFC.{{cite journal |last1=Rolls |first1=ET |title=A non-reward attractor theory of depression. |journal=Neuroscience and Biobehavioral Reviews |date=September 2016 |volume=68 |pages=47–58 |doi=10.1016/j.neubiorev.2016.05.007 |pmid=27181908|s2cid=8145667 |url=http://wrap.warwick.ac.uk/80548/1/WRAP_Rolls_depression16c.pdf }} Hypoactivity of the lateral OFC has been frequently observed in bipolar disorder, in particular during manic episodes.

Using functional magnetic resonance imaging (fMRI) to image the human OFC is a challenge, because this brain region is in proximity to the air-filled sinuses. This means that artifact errors can occur in the signal processing, causing, for example, geometric distortions that are common when using echo-planar imaging (EPI) at higher magnetic field strengths. Extra care is therefore recommended for obtaining a good signal from the orbitofrontal cortex, and a number of strategies have been devised, such as automatic shimming at high static magnetic field strengths.{{cite journal

| pmid = 12377170

| author = J. Wilson

| author2 = M. Jenkinson

| author3 = I. E. T. de Araujo

| author4 = Morten L. Kringelbach

| author4-link = Morten L. Kringelbach

| author5 = E. T. Rolls

| author5-link = E. T. Rolls

| author6 = Peter Jezzard

| author6-link = Peter Jezzard

| name-list-style = amp

| date = October 2002

| title = Fast, fully automated global and local magnetic field optimization for fMRI of the human brain

| journal = NeuroImage

| volume = 17

| issue = 2

| pages = 967–976

| doi = 10.1016/S1053-8119(02)91172-9

}}

In rodents, the OFC is entirely agranular or dysgranular. The OFC is divided into ventrolateral (VLO), lateral (LO), medial (MO) and dorsolateral (DLO) regions. Using highly specific techniques to manipulate circuitry, such as optogenetics, the OFC has been implicated in OCD like behaviors,{{cite journal |last1=Ahmari |first1=SE |title=Dissecting Ocd Circuits: From Animal Models to Targeted Treatments |last2=Dougherty |first2=DD |journal=Depression and Anxiety |date=August 2015 |volume=32 |issue=8 |pages=550–62 |doi=10.1002/da.22367 |pmid=25952989 |pmc=4515165}} and in the ability to use latent variables in decision-making task.{{Cite journal|last1=Vertechi|first1=Pietro|last2=Lottem|first2=Eran|last3=Sarra|first3=Dario|last4=Godinho|first4=Beatriz|last5=Treves|first5=Isaac|last6=Quendera|first6=Tiago|last7=Lohuis|first7=Matthijs Nicolai Oude|last8=Mainen|first8=Zachary F.|date=2020-04-08|title=Inference-Based Decisions in a Hidden State Foraging Task: Differential Contributions of Prefrontal Cortical Areas|url= |journal=Neuron|language=en|volume=106|issue=1|pages=166–176.e6|doi=10.1016/j.neuron.2020.01.017|issn=0896-6273|pmid=32048995|pmc=7146546|doi-access=free}}

Destruction of the OFC through acquired brain injury typically leads to a pattern of disinhibited behaviour. Examples include swearing excessively, hypersexuality, poor social interaction, compulsive gambling, drug use (including alcohol and tobacco), and poor empathising ability. Disinhibited behaviour by patients with some forms of frontotemporal dementia is thought to be caused by degeneration of the OFC.{{cite journal |author1=Snowden J. S. |author2=Bathgate D. |author3=Varma A. |author4=Blackshaw A. |author5=Gibbons Z. C. |author6=Neary D. | year = 2001 | title = Distinct behavioural profiles in frontotemporal dementia and semantic dementia | journal = J Neurol Neurosurg Psychiatry | volume = 70 | issue = 3| pages = 323–332 | doi=10.1136/jnnp.70.3.323|pmid=11181853 |pmc=1737271 }}

When OFC connections are disrupted, a number of cognitive, behavioral, and emotional consequences may arise. Research supports that the main disorders associated with dysregulated OFC connectivity/circuitry center around decision-making, emotion regulation, impulsive control, and reward expectation.{{Cite journal|last1=Xiao|first1=Xiong|last2=Deng|first2=Hanfei|last3=Wei|first3=Lei|last4=Huang|first4=Yanwang|last5=Wang|first5=Zuoren|date=September 2016|title=Neural activity of orbitofrontal cortex contributes to control of waiting|url=https://pubmed.ncbi.nlm.nih.gov/27336203/|journal=The European Journal of Neuroscience|volume=44|issue=6|pages=2300–2313|doi=10.1111/ejn.13320|issn=1460-9568|pmid=27336203|s2cid=205105682}}{{cite journal |author1=Paulus M. P. |author2=Hozack N. E. |author3=Zauscher B. E. |author4=Frank L. |author5=Brown G. G. |author6=Braff D. L. |author7=Schuckit M. A. | year = 2002 | title = Behavioral and Functional Neuroimaging Evidence for Prefrontal Dysfunction in Methamphetamine-Dependent Subjects | doi = 10.1016/s0893-133x(01)00334-7 |pmid=11751032 | journal = Neuropsychopharmacology | volume = 26 | issue = 1 | pages = 53–63 |doi-access=free }}{{cite journal |author1=Toplak M. E. |author2=Jain U. |author3=Tannock R. | year = 2005 | title = Executive and motivational processes in adolescents with Attention-Deficit-Hyperactivity Disorder (ADHD) | journal = Behavioral and Brain Functions | volume = 1 | issue = 1| pages = 8–20 |doi=10.1186/1744-9081-1-8 |pmid=15982413 |pmc=1183187 |doi-access=free }}{{cite journal |author1=Verdejo-Garcia A. |author2=Bechara A. |author3=Recknor E. C. |author4=Perez-Garcia M. | year = 2006 | title = Executive dysfunction in substance dependent individuals during drug use and abstinence: An examination of the behavioral, cognitive and emotional correlates of addiction | journal = Journal of the International Neuropsychological Society | volume = 12 | issue = 3| pages = 405–415 | doi=10.1017/s1355617706060486 | pmid=16903133|s2cid=15939155 }} A recent multi-modal human neuroimaging study shows disrupted structural and functional connectivity of the OFC with the subcortical limbic structures (e.g., amygdala or hippocampus) and other frontal regions (e.g., dorsal prefrontal cortex or anterior cingulate cortex) correlates with abnormal OFC affect (e.g., fear) processing in clinically anxious adults.{{Cite journal|title = Circuit-Wide Structural and Functional Measures Predict Ventromedial Prefrontal Cortex Fear Generalization: Implications for Generalized Anxiety Disorder|journal = The Journal of Neuroscience|date = 2014-03-12|issn = 0270-6474|pmid = 24623781|pmc = 6705282|pages = 4043–4053|volume = 34|issue = 11|doi = 10.1523/JNEUROSCI.3372-13.2014|first1 = Jiook|last1 = Cha|first2 = Tsafrir|last2 = Greenberg|first3 = Joshua M.|last3 = Carlson|first4 = Daniel J.|last4 = DeDora|first5 = Greg|last5 = Hajcak|first6 = Lilianne R.|last6 = Mujica-Parodi}}

One clear extension of problems with decision-making is drug addiction/substance dependence, which can result from disruption of the striato-thalamo-orbitofrontal circuit.{{cite journal |author1=Volkow N.D. |author2=Fowler J.S. | year = 2000 | title = Addiction a disease of compulsion and drive: involvement of the orbitofrontal cortex | journal = Cerebral Cortex | volume = 10 | issue = 3| pages = 318–325 | doi=10.1093/cercor/10.3.318|pmid=10731226 | doi-access = free }} Attention deficit hyperactivity disorder (ADHD) have also been implicated in dysfunction of neural reward circuitry controlling motivation, reward, and impulsivity, including OFC systems. Other disorders of executive functioning and impulse control may be affected by OFC circuitry dysregulation, such as obsessive–compulsive disorder and trichotillomania{{cite journal |author1=Chamberlain S. R. |author2=Odlaug B. L. |author3=Boulougouris V. |author4=Fineberg N. A. |author5=Grant J. E. | year = 2009 | title = Trichotillomania: Neurobiology and treatment | doi = 10.1016/j.neubiorev.2009.02.002 |pmid=19428495 | journal = Neuroscience and Biobehavioral Reviews | volume = 33 | issue = 6| pages = 831–842 |s2cid=6956143 }}{{cite journal | author = Menzies L. | year = 2008 | title = Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited | journal = Neuroscience and Biobehavioral Reviews | volume = 32 | issue = 3| pages = 525–549 | doi=10.1016/j.neubiorev.2007.09.005| pmid = 18061263 | pmc = 2889493}}{{cite journal |author1=Tekin S. |author2=Cummings J. L. | year = 2002 | title = Frontal-subcortical neuronal circuits and clinical neuropsychiatry: An update | journal = Journal of Psychosomatic Research | volume = 53 | issue = 2| pages = 647–654 | doi=10.1016/s0022-3999(02)00428-2|pmid=12169339 }}

Some dementias are also associated with OFC connectivity disruptions. The behavioral variant of frontotemporal dementia{{cite journal |author1=Rahman S. |author2=Sahakian B. J. |author3=Hodges J. R. |author4=Rogers R. D. |author5=Robbins T. W. | year = 1999 | title = Specific cognitive deficits in early behavioural variant frontotemporal dementia | journal = Brain | volume = 122 | issue = 8| pages = 1469–1493 | doi=10.1093/brain/122.8.1469 | pmid=10430832| doi-access=free }} is associated with neural atrophy patterns of white and gray matter projection fibers involved with OFC connectivity.{{cite journal |author1=Seeley W. W. |author2=Crawford R. |author3=Rascovsky K. |author4=Kramer J. H. |author5=Weiner M. |author6=Miller B. L. |author7=Gorno-Tempini L. | year = 2008 | title = Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia | journal = Archives of Neurology | volume = 65 | issue = 2| pages = 249–255 | doi=10.1001/archneurol.2007.38 | pmid=18268196 | pmc=2544627}} Finally, some research suggests that later stages of Alzheimer's disease can be impacted by altered connectivity of OFC systems.

Orbitofrontal epilepsy is rare, but does occur. The presentation of OFC epilepsy is fairly diverse, although common characteristics include sleep-related symptoms, automatisms, and hypermotor symptoms. One review reported that auras were generally not common or nonspecific, while another reported that OFC epilepsy was associated with auras involving somatosensory phenomena and fear.{{cite journal |last1=Chibane |first1=IS |last2=Boucher |first2=O |last3=Dubeau |first3=F |last4=Tran |first4=TPY |last5=Mohamed |first5=I |last6=McLachlan |first6=R |last7=Sadler |first7=RM |last8=Desbiens |first8=R |last9=Carmant |first9=L |last10=Nguyen |first10=DK |title=Orbitofrontal epilepsy: Case series and review of literature. |journal=Epilepsy & Behavior |date=November 2017 |volume=76 |pages=32–38 |doi=10.1016/j.yebeh.2017.08.038 |pmid=28928072|s2cid=13656956 }}{{cite journal |last1=Gold |first1=JA |last2=Sher |first2=Y |last3=Maldonado |first3=JR |title=Frontal Lobe Epilepsy: A Primer for Psychiatrists and a Systematic Review of Psychiatric Manifestations. |journal=Psychosomatics |date=2016 |volume=57 |issue=5 |pages=445–64 |doi=10.1016/j.psym.2016.05.005 |pmid=27494984}}{{cite journal |last1=Smith |first1=JR |last2=Sillay |first2=K |last3=Winkler |first3=P |last4=King |first4=DW |last5=Loring |first5=DW |title=Orbitofrontal epilepsy: electroclinical analysis of surgical cases and literature review. |journal=Stereotactic and Functional Neurosurgery |date=2004 |volume=82 |issue=1 |pages=20–5 |doi=10.1159/000076656 |pmid=15007215|s2cid=18811550 |url=https://epub.ub.uni-muenchen.de/16334/ }}

The visual discrimination test has two components. In the first component, "reversal learning", participants are presented with one of two pictures, A and B. They learn that they will be rewarded if they press a button when picture A is displayed, but punished if they press the button when picture B is displayed. Once this rule has been established, the rule swaps. In other words, it is now correct to press the button for picture B, not picture A. Most healthy participants pick up on this rule reversal almost immediately, but patients with OFC damage continue to respond to the original pattern of reinforcement, although they are now being punished for persevering with it. Rolls et al.{{cite journal |author1=Rolls E. T. |author2=Hornak J. |author3=Wade D. |author4=McGrath J. | year = 1994 | title = Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage | journal = J Neurol Neurosurg Psychiatry | volume = 57 | issue = 12| pages = 1518–1524 | doi=10.1136/jnnp.57.12.1518|pmid=7798983 |pmc=1073235 }} noted that this pattern of behaviour is particularly unusual given that the patients reported that they understood the rule.

The second component of the test is "extinction". Again, participants learn to press the button for picture A, but not for picture B. However, this time, instead of the rules reversing, the rule changes altogether. Now the participant will be punished for pressing the button in response to either picture. The correct response is not to press the button at all, but people with OFC dysfunction find it difficult to resist the temptation to press the button despite being punished for it.

A simulation of real-life decision-making, the Iowa gambling task is widely used in cognition and emotion research.{{cite journal |author1=Bechara A. |author2=Damasio A. R. |author3=Damasio H. |author4=Anderson S.W. | year = 1994 | title = Insensitivity to future consequences following damage to human prefrontal cortex | journal = Cognition | volume = 50 | issue = 1–3| pages = 7–15 | doi=10.1016/0010-0277(94)90018-3 | pmid=8039375|s2cid=204981454 }} Participants are presented with four virtual decks of cards on a computer screen. They are told that each time they choose a card they stand to win some game money. They are told that the aim of the game is to win as much money as possible. Every so often, however, when they choose a card they will lose some money. The task is meant to be opaque. That is, participants are not meant to consciously work out the rule, and they are supposed to choose cards based on their "gut reaction." Two of the decks are "bad decks", which means that, over a long enough time, they will make a net loss; the other two decks are "good decks" and will make a net gain over time.

Most healthy participants sample cards from each deck, and after about 40 or 50 selections are fairly good at sticking to the good decks. Patients with OFC dysfunction, however, continue to perseverate with the bad decks, sometimes even though they know that they are losing money overall. Concurrent measurement of galvanic skin response shows that healthy participants show a "stress" reaction to hovering over the bad decks after only 10 trials, long before the conscious sensation that the decks are bad. By contrast, patients with OFC dysfunction never develop this physiological reaction to impending punishment. Bechara and his colleagues explain this in terms of the somatic marker hypothesis. The Iowa gambling task is currently being used by a number of research groups using fMRI to investigate which brain regions are activated by the task in healthy volunteers as well as clinical groups with conditions such as schizophrenia and obsessive compulsive disorder.

The faux pas test is a series of vignettes recounting a social occasion during which someone said something that should not have been said, or an awkward occurrence. The participant's task is to identify what was said that was awkward, why it was awkward, how people would have felt in reaction to the faux pas and to a factual control question. Although first designed for use in people on the autism spectrum,{{cite journal |author1=Stone V.E. |author2=Baron-Cohen S. |author3=Knight R. T. | year = 1998a | title = Frontal Lobe Contributions to Theory of Mind | journal = Journal of Medical Investigation | volume = 10 | issue = 5| pages = 640–656 | doi=10.1162/089892998562942 | pmid=9802997|citeseerx=10.1.1.330.1488 |s2cid=207724498 }} the test is also sensitive to patients with OFC dysfunction, who cannot judge when something socially awkward has happened despite appearing to understand the story perfectly well.

File:Orbital gyrus animation small2.gif|Orbital gyrus shown in red

File:Medial surface of cerebral cortex - gyri.png|Medial surface of cerebral cortex - gyri

File:Orbital gyrus viewed from bottom.png|Basal surface of cerebrum. Orbital gyrus shown in red.

Lateral Orbitofrontal - DK ATLAS.png|Lateral orbitofrontal cortex

Medial Orbitofrontal - DK ATLAS.png|Medial orbitofrontal cortex, inner slice view

File:Orbitofrontal cortex.gif|3D visualization of the orbitofrontal cortex in an average human brain

File:Orbitofrontal cortex coronal sections.gif|Orbitofrontal cortex highlighted in green on coronal T1 MRI images

File:Orbitofrontal cortex sagittal sections.gif|Orbitofrontal cortex highlighted in green on sagittal T1 MRI images

File:Orbitofrontal cortex transversal sections.gif|Orbitofrontal cortex highlighted in green on transversal T1 MRI images

• Reward system
• Witzelsucht

{{Reflist|30em}}

{{Commons category|Orbitofrontal cortex}}

• [https://web.archive.org/web/20051215175757/http://cercor.oxfordjournals.org/cgi/content/full/10/3/205 Cerebral Cortex special issue on orbitofrontal cortex]
• [https://web.archive.org/web/20070221124515/http://www.econ-pol.unisi.it/pubdocenti/coricellig/regret_science.pdf Camille et al. (2004) The Involvement of the Orbitofrontal Cortex in the Experience of Regret]

{{Prosencephalon}}

{{Obsessive–compulsive disorder}}

Category:Cerebral cortex

Category:Limbic system

Category:Frontal lobe