What Is The Orbitofrontal Cortex

The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 and 13; in humans it consists of Brodmann area 10, 11 and 47.

The orbitofrontal cortex (OFC) is considered anatomically synonymous with the ventromedial prefrontal cortex. Therefore, the region is distinguished due to the distinct neural connections and the distinct functions it performs.

It is defined as the part of the prefrontal cortex that receives projections from the magnocellular, medial nucleus of the mediodorsal thalamus, and is thought to represent emotion and reward in decision making.

It gets its name from its position immediately above the orbits in which the eyes are located.

Function Of The Orbitofrontal Cortex

It is suggested that the medial OFC is involved in making stimulus-reward associations and with the reinforcement of behavior, while the lateral OFC is involved in stimulus-outcome associations and the evaluation and possibly reversal of behavior. Activity in the lateral OFC is found, for example, when subjects encode new expectations about punishment and social reprisal. It is also found when suppressing negative emotions, especially in approach-avoidance situations, such as the game of chicken.

The lateral OFC plays an important role in conflict resolution and damage to this area results in both inappropriate displays of anger and inappropriate responses to the anger of others. For example, subjects with damage to the left lateral OFC have been found to be defensive and to present themselves in an “angelic light”. Low volume in this area has also been correlated with experiencing “fear of God”.

On the other hand, subjects with greater volume in this area have been found to score higher on the Mach IV test measuring Machiavellian personality traits and activity in this region has generally been connected with Machiavellian thinking .

In one study, adults who were classified as “high-reactive” as children, meaning shy and inhibited, were found to have greater cortical thickness in the right ventromedial prefrontal cortex, while adults who were classified as “low-reactive”, meaning outgoing and uninhibited, were found to have greater thickness in the left lateral orbitofrontal cortex.

In Humans

The human OFC is among the least-understood regions of the human brain; but 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. 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.

Human research has focused on neuroimaging research in healthy participants and neuropsychology research in patients with damage to discrete parts of the OFC. Research at the University of Leipzig shows that the human OFC is activated during intuitive coherence judgements.

Structure Of The Orbitofrontal Cortex

The OFC has been divided by structure and connections into a medial and a lateral part. The medial part is most strongly connected with the hippocampus and associated areas of the cingulate, retrosplenial and entorhinal cortices, anterior thalamus and septal diagonal band.

The lateral part can be further subdivided into three sectors. The most caudal sector is characterized by strong connections with the amygdala, midline thalamus, non-isocortical insula and temporal pole. The most anterior sector has more pronounced connections with the granular insula, association cortex, mediodorsal thalamus, inferior parietal lobule and dorsolateral PFC.

Connections

Tracer studies in monkeys have shown that the orbitofrontal cortex shares extensive connections with other association cortices, primary sensory and association cortices, limbic systems, and other subcortical areas. Corticocortical connections include extensive local projections to and from other prefrontal regions, as well as with motor, limbic, and sensory cortices. Areas projecting to motor areas are densely interconnected with other prefrontal cortical regions, reflecting integration for executive motor control.

Sensory cortices additionally share highly complex reciprocal connections with the orbitofrontal cortex. All sensory modalities are represented in connections with the orbitofrontal cortex, including extensive innervation from areas associated with olfaction and gustatory somatic responses.

Somatosensory cortices including primary areas 1 and 2, particularly in areas associated with innervation of the hand and trigeminal complex, indicating the importance of the orbitofrontal cortex in face and hand sensation.

Functionally distinct pathways for auditory processing in the orbitofrontal cortex include a rostral stream associated with phonetic processing, and a more caudal stream terminating just posterior to the orbitofrontal cortex in the periarcuate prefrontal cortex associated with auditory-spatial processing, though these connections share extensive overlap.

Both ventral and dorsal visual streams share connections with orbitofrontal cortical areas, including rich projections to and from the superior temporal pole, important for integration of spatial processing and object processing.

Connectivity of the orbitofrontal cortex with limbic areas includes reciprocal projections to granular, dysgranular, and agranular insular cortex, parahippocampal regions, and the hippocampus, particularly CA1 regions in a rostral-to caudal gradient. The orbitofrontal cortex additionally shares extensive reciprocal connections with the amygdala, and direct and indirect connections to the hypothalamus.

Additional subcortical projections are shared between the striatum, particularly ventral reward-related areas. Connectivity with thalamic and periaqueductal grey areas further suggests a role for the orbitofrontal cortex in both inhibitory and excitatory regulation of autonomic function.

Parallel processing loops in connectivity between cortico-striatal networks seem to be involved in the processing of goal-directed and habitual action, whereas cortico-limbic connectivity seems to be of prime importance for action selection, implicating the basolateral amygdala, and the integration of information into behavioral output.

The connections between orbitofrontal cortex and amygdala play a notable role in emotional decision making process. These connections contribute in modulating the associative learning process and emotion regulation in the amygdala.

Though invasive tracer studies are largely not possible in humans, diffusion tensor imaging (DTI) tractography studies have also been used to map the connectivity of the orbitofrontal cortex to cortical and subcortical brain structures. Connections in the human orbitofrontal cortex follow a conserved pattern, similar to what is shown in tracer studies in rhesus macaques, but with a distinct pattern of connectivity with regions of the striatum.

OFC Clinical Significance

Addiction

Involvement of the OFC is often implicated in addictive behavior in addition to the nucleus accumbens and amygdala. The striato-thalamo-orbitofrontal circuit of the OFC has been implicated in the development of addictive behavior via dopaminergic activation of reward circuits as supported by brain imaging studies.

The OFC has been associated with compulsive behavior and repetitive behavior, as well as with drive; in drug dependent individuals, disruption of the striato-thalamo- orbitofrontal circuit leads to compulsive behavior and increased motivation to take the drug.

Addicted individuals show deficits in orbitofrontal, striatal, and thalamic regions. Conscious and unconscious components are hypothesized to serve as mechanisms responsible for the maintenance of drug addiction: conscious mechanisms involve craving associated with loss of control and unconscious elements include anticipated conditioned responses to a drug and impulsivity.

Brain imaging studies show that during cocaine withdrawal, metabolism is increased in the OFC and that this is proportional to drug craving. In contrast, during protracted (up to 3–4 months) withdrawal cocaine abusers show reduced activity in the OFC compared to healthy controls.

Similarly, in alcoholics, during withdrawal there is decreased activity in the OFC (compared to the OFCs of healthy controls) but, in addition, detoxified alcoholics have significantly lower levels of benzodiazepine receptors in the OFC (compared with healthy controls). Hypoactivity in the OFC of alcoholics is also supported by blunted metabolism in the OFC to response to both serotonogenic and GABA– ergic agents.

However, in heroin addiction, a neuroimaging study shows that brain resting-state functional connectivity in the OFC is enhanced in heroin-dependent individuals during abstinence.

Damage

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.

Disruption

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, and reward expectation.

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.

One clear extension of problems with decision-making is drug addiction/substance dependence, which can result from disruption of the striato-thalamo-orbitofrontal circuit. Attention deficit hyperactivity disorder (ADHD) has 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

Some dementias are also associated with OFC connectivity disruptions. The behavioral variant of frontotemporal dementia is associated with neural atrophy patterns of white and gray matter projection fibers involved with OFC connectivity. Finally, some research suggests that later stages of Alzheimer’s Disease be impacted by altered connectivity of OFC systems.

Barbas H, Ghashghaei H, Rempel-Clower N, Xiao D (2002)
Anatomic basis of functional specialization in prefrontal cortices in primates.
Handbook of Neuropsychology (Grafman J, ed), Amsterdam: Elsevier Science B.V.

Top Image: MRI region highlighted shows approximate location of the orbitofrontal cortex. By Paul Wicks via Wikimedia Commons.