[3] It is defined as the part of the prefrontal cortex that receives projections from the medial dorsal nucleus of the thalamus, and is thought to represent emotion, taste, smell and reward in decision making.

[16] These caudal regions, which sometimes include parts of the insular cortex, respond primarily to unprocessed sensory cues.

The caudal OFC is more heavily interconnected with sensory regions, notably receiving direct input from the pyriform cortex.

[18] 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.

[21][23] The orbitofrontal cortex is reciprocally connected with the perirhinal and entorhinal cortices,[23] the amygdala, the hypothalamus, and parts of the medial temporal lobe.

[36] 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.

[39] Activity in the lateral OFC is found, for example, when subjects encode new expectations about punishment and social reprisal.

[43] Neurons in the OFC respond both to primary reinforcers, as well as cues that predict rewards across multiple sensory domains.

In contrast to the medial prefrontal cortex and striatum, OFC neurons do not exhibit firing mediating by movement.

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.

[47] 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.

[50] 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.

OCD has been proposed to reflect a positive feedback loop due to mutual excitation of the OFC and subcortical structures.

[55] Animal models and cell-specific manipulations in relation to drug-seeking behavior implicate dysfunction of the OFC in addiction.

[56] Substance use disorders are associated with a variety of deficits related to flexible goal directed behavior and decision making.

[57] Rodent studies also demonstrate that lOFC to BLA projections are necessary for cue induced reinstatement of self administration.

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.

[16] The OFC is divided into ventrolateral (VLO), lateral (LO), medial (MO) and dorsolateral (DLO) regions.

[19] Using highly specific techniques to manipulate circuitry, such as optogenetics, the OFC has been implicated in OCD like behaviors,[66] and in the ability to use latent variables in decision making task.

[67] Destruction of the OFC through acquired brain injury typically leads to a pattern of disinhibited behaviour.

Research supports that the main disorders associated with dysregulated OFC connectivity/circuitry center around decision-making, emotion regulation, impulsive control, and reward expectation.

[69][70][71][72] 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.

The behavioral variant of frontotemporal dementia[78] is associated with neural atrophy patterns of white and gray matter projection fibers involved with OFC connectivity.

[79] Finally, some research suggests that later stages of Alzheimer's disease can be impacted by altered connectivity of OFC systems.

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.

A simulation of real life decision-making, the Iowa gambling task is widely used in cognition and emotion research.

Although first designed for use in people on the autism spectrum,[85] 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.