Phineas Gage and the Orbitofrontal Cortex

 

The day of September 13, 1848 marked the beginning of research involving the relationship between the prefrontal lobe and human behavior. Phineas Gage, a railroad foreman, was unearthing rock when a thick piece of iron smashed through the left side of his face. It entered below the cheekbone and came out through his skull. People were shocked when the blow did not kill him, and even more amazed that he was able to speak within a few minutes. Dr. John Martin Harlow, the attending physician, observed the changes in Gage’s personality for the next thirteen years until Gage died from a series of epileptic seizures, and also convinced his family to allow his skull to be exhumed five years later. Before the accident, Gage was known as a competent and adept employee; after the accident, he was rude, impulsive, profane, and negligent. His rational thinking and emotional processing was so impaired that he lost his job. Harlow’s reports, though not readily accepted, were confirmed for the most part by an experiment on monkeys in 1878; thus the analysis of the prefrontal lobes began (Larner & Leach, 2002).

The prefrontal lobe is responsible for formulating plans and strategies, along with a person’s “personality” (Carson, 2004, 84). The orbitofrontal cortex (OFC), part of prefrontal lobes, is located at the base of the frontal lobes right about the eyes. This cortex makes up an important part of who we are by regulating our emotions. The OFC receives input from the dorsomedial thalamus and the temporal cortex (both linked to memory); the ventral tegmental area (associated with the reward system); the olfactory system; and the amygdala, which is tied to anger. It then sends signals to the branches of the limbic system (responsible for moods and emotions) including: the cingulate cortex, the hippocampal formation, the temporal cortex, the lateral hypothalamus, and the amygdala; along with other areas of the frontal lobe. The inputs consist of environmental information, and the outputs regulate one’s behavior and physiological responses, essentially emotion. These inputs and outputs help establish the OFC as an interface between brain mechanisms, such as automatic learned and unlearned emotional reactions, along with complex behaviors (351-352).

Studying primates’ brains and behaviors is a good way to learn about the OFC; unfortunately, rodents’ orbitofrontal cortexes are too small to get significant information from. Some researchers consider the OFC the secondary taste cortex because it receives stimuli from the primary taste cortex in primates. Taste can act as a primary reinforcer; therefore, the OFC taste neurons are controlled by hunger. For instance, a monkey will eat until it is full. Once full, the OFC neurons no longer respond; whereas, the neurons of the primary taste cortex are regulated by the identity of taste, not the reward value. Therefore, the reward value of taste is represented in the OFC. One area of the OFC responds to sweet tastes (those with glucose), while another is activated by the taste of salt. This concept goes for pleasant touch, nice smells, and also foul smells; each works in a different area of OFC. Fatty foods give off a pleasant sensation because the brain knows these foods will probably contain high calories and essential fatty acids. There are even OFC neurons that respond to textures and temperature of food (Rolls, 2004).

It has been shown that smells activate neurons in the OFC of monkeys and in the ventral front region of humans. Thirty-five percent of these neurons are influenced by taste association, while the other sixty-five percent are completely dependent on the odor itself. Just as in taste, the OFC neuron activity decreases when monkeys are full, and the value of odor is represented in this cortex. In addition, the inferior temporal cortex sends visual inputs directly to the OFC. Individuals react differently to items or images depending on their reward association. For example, OFC face-responsive neurons convey signals to one by sending different responses for dissimilar faces and expressions. This is also a method of reinforcement; an area of the OFC responds to face expression by signifying behavior should change. Somatosensory inputs (touch, pain, etc.) are sent from the postcentral gyrus; and the amygdala transmits signals to the caudal (“tail end”) of the OFC. The more pleasure and pain there is, the more OFC activity occurs. Patients with damage to the ventral part of the frontal lobe may feel pain, but report that it does not feel very bad (Rolls, 2004).

As it is clear to see, the OFC takes care of many important functions by combining sensory observations and the reward system, among other things. As a result, when this area of the brain is damaged, many behavioral abnormalities will arise. Inappropriate behavior and emotional changes are imminent, as seen in the Phineas Gage case. Patients will become more impulsive, along with performing worse with stimulus-reinforcement associations. They typically show greater unprovoked emotions of anger and less unwarranted happiness. Also, their sense of time is impaired. In my opinion, the impulsive nature they display may partially be attributed to their belief that time is moving faster (Berline, Rolls, & Kischka, 2004). Misinterpretations of others’ moods, lack of initiative, and unconcern or underestimation of the gravity of a situation are all side effects that hinder patients’ relationships and every day lives. Frontal lobe damage can cause patients to be unable to plan or correct certain behaviors, though they can verbally express the right course of action (Rolls, 2004). Individuals that have lesions on their dorsolateral prefrontal cortex display problems with spatial working memory, unlike people with damage to the OFC (Berline, et al., 2004).

The ability to respond to social reinforcers and the reward system are an essential part of any primate’s life. Not knowing how to respond to facial expressions on someone can be hazardous. What an OFC patient might consider to be a joking expression may be anything but that. Some patients also have problems with voice recognition, but both face and voice recognition problems do not always occur together. “Bilateral surgically circumscribed (but not usually unilateral) lesions of the human orbitofrontal cortex produce deficits in a probabilistic version of a visual discrimination reversal task with monetary reward (Rolls, 2004). For instance, when a person is gambling and receives money, the medial OFC is activated; when a person loses money, the lateral OFC is activated. In a person with normal OFC activity, a person will have better control when gambling because his or her OFC alerts the individual to be aware of the dangers of losing. Someone with damage to this cortex may not have any apprehensions when betting and any bad feelings when losing (Rolls, 2004). Believe it or not, even bladder control is related to the OFC. Patients with bladder control problems show little activity in this area when their bladders are full, compared to individuals with normal activity (Swyers, 2006).

Many patients with mental disorders have abnormal activity in their OFC. Unsurprisingly, research has revealed that patients with bipolar disorder, which has characteristics of extreme mood swings, have abnormalities in several brain areas that control emotion. The amygdala and hippocampus are smaller in both children and adults, which suggests that even though symptoms may not progress until a later time, brain changes are an early feature in this disorder. Frontal areas of the brain, such as the OFC and anterior cingulate also show abnormalities. These irregularities may be caused by a gene known as BDNF, which produces a factor involved in the development of brain structures. When bipolar patients were depressed, the activity in the OFC was extremely high; when the patients were manic, the activity was very low. This occurrence makes sense because patients with OFC damage are impulsive and easily agitated, much like manic bipolar patients; whereas, people that had an overly active OFC would most likely be overly emotional (Bipolar 2003). Another great reference site for this phenomenon is located at http://www.neurotransmitter.net/bipolarpfc.html; it reports many studies dealing with the aforementioned topic. In post traumatic stress disorder, the amygdala and associated areas are activated by traumatic stimuli. The OFC is less capable of inhibiting the activation; and the activation of the amygdala, along with neurotransmitter and endocrine activity, produce many of the symptoms in PTSD (Excerpt, 2005). Patients with obsessive compulsive disorder show heightened activity in the OFC and anterior cingulate gyrus. The hyperactivity of these areas cause excessive signals to be sent to the basal ganglia; which in turn, causes patients to report a feeling that something is wrong (Gladding, 1999).

In conclusion, the orbitofrontal cortex and frontal lobes play a vital part in regulating our emotions and behaviors. Though unfortunate, the accident that Phineas Gage was involved in provided an important building block for research of this brain area. Many disorders show abnormal orbitofrontal activity, and further research is sure to explore this fascinating structure.
References:

1. Berlin, H.A., Rolls, E.T., Kischka, U. (2004). Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions [electronic source]. Oxford Journals, 127, 1108-1126.

2. Bipolar Disorder and the Brain. (2003). Society for Neuroscience. Retrieved February 5, 2006, from http://apu.sfn.org/content/Publications/BrainBriefings/bipolar_disorder.htm

3. Excerpt from Posttraumatic Stress Disorder. (2005). Emedicine. Retrieved February 7, 2006, from http://www.emedicine.com/med/byname/posttraumatic-stress-disorder.htm

4. Carlson, Neil R. (2004). Physiology of Behavior, 8.

5. Gladding, Becky. (1999). Neurobiology for Obsessive-Compulsive Disorder (OCD). Westwood Institute for Anxiety Disorders. Retrieved February 7, 2006, from http://www.hope4ocd.com/research/schwartz1299.html

6. Larner, AJ & Leach, JP. (2002). Phineas Gage and the beginnings of neuropsychology [Electronic Source]. History of Neurology & Neuroscience. ACNR, Vol. 2, No. 3, 26.

7. Rolls, Edmund. (2004). Convergence of Sensory Systems in the Orbitofrontal Cortex in Primates and Brain Design for Emotion [Electronic Version]. The Anatomical Record Part A, 281A, 1212-1225.

8. Swyers, Jim. (2006). Overactive Bladder Related To Orbitofrontal Cortex Activity. Retrieved February 7, 2006 from http://www.medicalnewstoday.com/medicalnews.php?newsid=36593