Functions of prefrontal cortex, A story of Phineas P. Gage

The anatomical definitions
The prefrontal cortex is part of the frontal lobe, which initially is used to describe the anterior portion of the brain. However, dues to the accumulation of knowledge towards neuroanatomical function of prefrontal cortex, this terminology is leaning forward into a functional term, the executive function. Various definitions exist for prefrontal cortex, but this author preferred the prefrontal cortex to be defined as the frontal cerebral cortex that received projections from mediodorsal nucleus of thalamus, and its correlate to Brodmann’s area predominantly area 9, 44, & 45; and area 10, 11, & 12. It is important to know that mediodorsal thalamus has tremendous projections to various cerebral regions and prefrontal cortex also has a large amount of reciprocal connections with other cerebral region such as the association cortex and other thalamic nucleus. Anterior cingulate cortex, which is part of the limbic system, has been included in the prefrontal cortex. Please refer to the diagrammatic picture below for the location of prefrontal cortex.

prefrontal cortex

Image above shows the location of prefrontal cortex with the darker blue indicating the more predominant part from the mediodorsal thalamic projection.

A story of Phineas P. Gage, and what we have learnt.
A story that almost never missed in any neuroscience textbooks is a story of Phineas Gage. In September 1848, Phineas Gage, a 25 year old railroad construction foreman, has an extensive frontal lobe injury as a pointed tamping iron bar shot through the his skull by an explosion, from his left cheek, through his left orbit, and diagonally exit through his upper center part of his head (shown in picture below). The bar measured at 3.5 feet long and 1.25 inches in its greatest diameter. The remarkable part is that he survived! Although he survived, he has a dramatic change in his personality. A man who was once described as efficient, well-balanced, shrewd, and energetic is now become as described “fitful, irreverent, indulging at times in the grossest profanity, impatient if restraint or advice when it conflicts with his desires, obstinate, devising many plans of operation which are no sooner arranged than they abandoned in turn for others appearing more feasible” by Harlow, 1868. In short, “he is no longer Gage”. His intelligence, however, is salvaged. And this in combination with other observations of frontal lobe injury suggested that frontal lobe has a principle role in personality and emotion. It is not until mid-20th century that “executive function” was labeled into the frontal lobe, for which we now knew to be more specific is the prefrontal cortex.


Image above shows a pictorial representation of Phineas Gage’s rod penetration.
A story of prefrontal leucotomy.
In 1936, Moniz (neuropsychiatrist) and Lima (neurosurgeon) introduced a neurosurgical procedure known as the prefrontal leucotomy to disconnect the prefrontal cortex from the subcortical region (basal ganglia and thalamus) in order to modify the behavior of the psychotic patients. This procedure did in many cases, helps in reduction of anxiety and mania of the patients. However, this leads to a new problem, impairments in emotion and cognition. These patients became impulsive and poor in attention. They are easily distracted, and often unable to control their urge for which they act on instinct regardless of the consequences. They are also poor in judgments and was unable to make plans for future goal.
Prefrontal cortex’s functions: the executive control
As a general rule, the prefrontal cortex is well known for its function in executive control. This encompasses a wide spectrum of processes that include attention, working memory, flexibility of thought, motor sequencing, planning, and the regulation of goal directed behavior. Based on the previous statement, you would have predicted the loss if prefrontal cortex is destroyed. You’re right; one would become rigid in thought, impulsive, poor in planning, lack of emotion self-control, and sometimes, lack of motivation.
In prefrontal cortex, it can be divided into 3 regions, which is the lateral dorsal cortex, the medial, and the orbital. All of these regions are concerned with executive function in general. There are some differences in their functions and is inevitably overlapped. The lateral dorsal cortex is correlated with motor association of executive function, while the medial and orbital correlate with limbic emotional control of executive function. Even more interesting, a tumor that grows underneath the prefrontal cortex, as its progresses upwards, would result not only a personality disturbances but also instinctive tactile grasp reflex, suckling reflex (all these are primitive reflexes that exist in infants and should be absent in older age) and urinary or bowel incontinence.

Breaking down the prefrontal cortex.

The function of prefrontal cortex can be further broken down based on their sub-regions as mentioned previously.
A) Dorsolateral cortex (upper and outer)
In studies of chimpanzees, there is an impairment in working memory (memory that enable you dial the numbers after temporarily memorizing the telephone number you have just listened) if the dorsolateral cortex is damaged. Patients with dorsolateral would shows to be rigid and concrete in thought (lack of flexibility), and also lack of abstract thinking.
B) Lateral orbital (lower and outer)
In humans, one would demonstrate restlessness, hyperkinesis (overactive restlessness with excessive unwanted movement), explosive, and impulsive behavior.
C) Frontal pole and/or medial aspect of both prefrontal cortexes.
A syndrome of pseudo-depression is manifested. They presented with apathy, lack of concern, lack of motivational drive and also lack of emotional activity. Sometimes, it would be more severe and akinetic mutism (they neither move nor do they speak) would occurs.
D) Ventromedial/orbital lesion (lower and inner)
This give us a pseudo-psychopathology syndrome manifest as inability to inhibit facetiousness (treating a serious issues with an inappropriate humors), sexual and personal self-indulgence that is poorly controlled, delusions of grandeur (fantasy believes that oneself is famous, rich or powerful), and lack of concerns for others.
E) Anterior cingulate cortex
This interconnect with orbitofrontal cortex, which is involved in behavioural drive followed by the evaluation of the outcomes dues to that particular behaviour. One important function is to allow a person to infer what the other person might be thinking or feeling in response to a specific events. Damaged to this area will result impairment in this area of functions.


1. Joaquin M. Fuster, ed. The prefrontal cortex. Fourth edition. Elsevier, United Kingdom, UK. 2008.

2. Elliott L. Mancall and David G. Brock, ed. Gray’s clinical neuroanatomy: the anatomical basis for clinical neuroscience. First edition. Elsevier Saunders, Philadelphia. PA. 2011.

3. Stanley Jacobson and Elliott M. Marcus, ed. Neuroanatomy for neuroscience. Springer, Boston. MA. 2008.

4. Eduardo E. Benarroch et al., ed. Mayo Clinic Medical Neurosciences: organized by neurological systems and levels. Fifth edition. Mayo Clinic Scientific Press. Rochester, MN. 2008

5. Bruce L. Miller and Jeffrey L. Cummings, ed. The human frontal lobes: functions and disorders. Second editions. Guilford Press. New York, NY. 2007


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