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Chapter III. The Neurological Basis of Conscious Experience >> The role of the Prefrontal cortex in mental synthesis

The role of the Prefrontal cortex in mental synthesis

We have already discussed the process of conscious experience in both the physical and imaginary worlds. To a large extent, the conscious experience in the physical world is controlled by external stimuli. The natural question is, what part of the brain is controlling the conscious experience in the imaginary world? For humans, the conscious experience in the imaginary world is inseparable from mental synthesis. Thus, the question is, what part of brain executes mental synthesis?

There are strong indications that mental synthesis is primarily executed by the prefrontal cortex. In a simplistic scenario, the prefrontal cortex synchronizes several ensembles of neurons from memory stored elsewhere in the cortex with the attention rhythm. In this process, the prefrontal cortex synthesizes new mental constructs and allows mental planning and problem solving.

The prefrontal cortex is the very frontal part of the brain: in front of the motor and premotor areas. It is located right beneath the forehead. In terms of its cellular composition, the prefrontal cortex is defined by the presence of an internal granular layer IV (in contrast to the agranular premotor cortex). The prefrontal cortex is responsible for executive functions, which include planning complex cognitive behavior, personality expression and moderating correct social behavior.

In fact, the prefrontal cortex has been implicated in the planning of complex cognitive behaviors. Patients with damage in the prefrontal cortex exhibit a lack of ability to predict outcomes, a reduction in the ability to suppress urges, difficulty in making a determination of whether things are the same or different, and have other deficits in so-called executive functions. These patients pursue behavior that is aimed at immediate gratification despite the fact that longer-term results could be detrimental. Let us begin our introduction to the role of the prefrontal cortex with the seminal case of Phineas Gage.

Changes in Phineas Gage’s character following bilateral damage of frontal lobes

Phineas Gage (1823-1860) was a railroad foreman clearing the roadbed for a new rail-line outside the town of Cavendish, Vermont. To blast the rock, workers had to drill a hole in the rock, fill the hole with gunpowder, add a fuse and sand, and then pack the charge down with a tamping iron. On September 13, 1848, possibly because the sand was omitted, the powder exploded, throwing the tamping iron through Gage’s head. The iron rod, weighing 6 kg (13 lb), was propelled with such force that it landed some 25 meters (80 feet) from Phineas Gage.

The drawing of Phineas Gage’s skull reprinted from Harlow's 1868 paper: "Front and lateral view of the cranium, representing the direction in which the iron traversed its cavity; the present appearance of the line of fracture, and also the large anterior fragment of the frontal bone, which was entirely detached, replaced and partially re-united." The skull and the tamping iron are on display at the Warren Medical Museum of Harvard University, Boston, USA.

Computer generated model shows how the tamping iron may have impacted Phineas Gage's frontal lobes.

The iron rod entered through the side of the face, shattered the upper jaw, passed behind the left eye, partially damaged both frontal lobes and exited at the top of the head. The destruction of brain tissue was likely reduced by the fact that the iron rod was tapered to a 1/4-inch point at the leading end.

To everybody’s surprise, Phineas Gage spoke within minutes and walked with little assistance to a cart that carried him to a physician. Gage recovered nearly completely except for loss of vision in his left eye and some facial paralysis. By May of 1849 he felt strong enough to resume work, but his employers refused to return him to his previous position because of mental changes. Dr. John Martyn Harlow described the pre-accident Gage as having been hard-working, responsible, and popular with the men in his charge, but the post-accident Gage as “fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man. Previous to his injury, although untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage’.”

Although Phineas Gage’s memory, speech and motor skills remained intact, his personality changed radically. As pointed out by Dr. Harlow and several other people, he was "no longer Gage": irritable, quick-tempered, and impatient, with a lack of foresight.

Despite the changes in character, Phineas Gage worked first in a livery stable in New Hampshire and then as a coach driver for seven years in Chile, South America. Due to failing health, he returned to San Francisco to his mother and sister in 1859. He died in May of 1860 following a series of increasingly debilitating convulsions.

The fact that Phineas’ memory, speech and motor skills remained intact following bilateral damage to the prefrontal cortex indicates that areas responsible for those functions are located elsewhere in the cortex. Further, Phineas’ ability to work as a coach driver for seven years indicates that his visual abilities (visual analysis, object identification, and orientation in space) were intact. Phineas’ only problem was changes in his character due to a lack of foresight. Foresight and planning are intricately connected to mental synthesis. Thus, Phineas’ lack of foresight is probably explained by his reduced capacity for execution of mental synthesis. This links the prefrontal cortex to the function of execution of mental synthesis.

Lobotomy

Between the years 1935 and 1986, over 70,000 patients worldwide underwent a surgical operation commonly known as lobotomy, which cuts the connection to the prefrontal cortex. The operation was pioneered by a Portuguese physician, António Egas Moniz, for treating severe mental abnormalities. The procedure was later refined by the American physician Walter Freeman and the neurosurgeon James W. Watts. It involved lifting the upper eyelid and placing the point of a thin stylus under the eyelid and against the top of the eye socket. A hammer was then used to drive the stylus through the thin layer of bone and into the brain. The stylus was then moved from side to side to sever the nerve fibers connecting the prefrontal cortex to the deeper brain structures. The procedure was normally performed on both sides.

Lobotomy often resulted in major personality changes, mental disabilities, or a complete loss of intellect. Among famous patients who underwent lobotomy was Rosemary Kennedy, the sister of President John F. Kennedy, who was born a year after her brother. In 1941, at the age of 23, she underwent a lobotomy when her father, Joseph Kennedy, complained to doctors about her "mood swings that the family found difficult to handle at home." Reportedly, Joseph Kennedy was also uncomfortable with Rosemary’s low intellectual abilities and promiscuity. Rosemary was apparently very fond of her father. At the age of 16 she wrote to her father: "I would do anything to make you so happy. I hate to disappoint you in any way." That affection may explain why she agreed to undergo the surgery.

Dr. Watts personally performed the procedure with Dr. Freeman observing. Rather than resulting in any improvement, the lobotomy reduced Rosemary to an infantile mentality that left her incontinent and staring blankly at walls for hours. Rosemary became largely detached from the Kennedy clan, and spent most of the time in institutions until her death in 2005.

Dr. Freeman proceeded to personally perform over 3,000 lobotomies. The practice of lobotomy ceased in the 1970s with the introduction of antipsychotic drugs.

Neurological deficits associated with damage to the prefrontal cortex

An excellent analysis of impairment in patients with prefrontal cortex damage is presented by A. R. Luria, an accomplished neuropsychologist: “These patients are unable to systematically analyze the conditions of a problem and to select the important connections within it … The selective system of operations that normally successively leads to the solution of the problem disintegrates and is replaced by a series of isolated, fragmentary connections, not subservient to the general plan and without a clearly defined hierarchical structure. … Complex problems, such as ‘A son is 5 years old; in 15 years his father will be twice as old as he. How old is his father now?’ are completely beyond the grasp of such patients. Without listening to the conditions, they at once begin to make such calculations as 15 × 5 = 75 or 3 × 15 = 45.” (Luria, 1966)

Another example involves the Tower Of London Test, which consists of two boards with pegs and colored beads. The configuration of the beads is different on the two boards. The subjects are asked to move the beads on one board in order to achieve the bead arrangement of the second board (goal position). The subjects are instructed to plan internally and to achieve the goal arrangement in as few moves as possible. Patients with damage to the prefrontal cortex are impaired at this task (Shallice, 1982; Owen, 1990; Owen, 1995).

The Tower Of London Test consists of two boards with pegs and colored beads. The configuration of the beads is different on the two boards. The subjects are asked to move the beads on one board in order to achieve the bead arrangement of the second board (goal position). The subjects are instructed to plan internally and to achieve the goal arrangement in as few moves as possible. Patients with damage to the prefrontal cortex are impaired at this task.

Burgess and colleagues described five patients with damage to the prefrontal cortex. In all five patients, their cognitive deficits included a failure to create and carry out intentions (Burgess, 2000).

In addition, patients with prefrontal cortex damage are significantly impaired in their ability to solve problems that require multi-dimensional integration, that is, mental synthesis of spatially distributed objects (Waltz, 1999; Duncan, 1995).

Thus, damage to the prefrontal cortex is associated with a reduction in the capacity for execution of mental synthesis. Smaller damage can lead to inappropriate social behavior, lack of foresight, and reduced ability to systematically analyze problems. Larger damage or disconnection of the prefrontal cortex from the rest of the brain can lead to a complete inability to perform mental synthesis as exemplified by the case of Rosemary Kennedy.

Functional imaging of the prefrontal cortex in normal subjects

There is a plethora of evidence provided by brain imaging that implicates the prefrontal cortex in tasks that involve mental synthesis:

1. Christoff and Gabrieli evaluated scientific literature and found evidence of significant activity in the prefrontal cortex in studies that involve problem solving (Christoff, 2000).

2. Baker and colleagues asked their subject to perform the Tower Of London Test while measuring brain activity with imaging technique. The scientists reported that the test activated the prefrontal cortex (Baker, 1996; Owen, 1996). This experiment is consistent with the hypothesis that planning (accomplished through mental synthesis) is executed by the prefrontal cortex.

3. Functional MRI data showed bilateral activity in the prefrontal cortex when subjects were asked to keep a main goal in mind while simultaneously performing sub-goals: a process generally required in planning and reasoning (Koechlin, 1999; Koechlin, 2000).

4. Several studies have observed the activity in the prefrontal cortex during the performance of automated, learned actions and compared it to the activity in the prefrontal cortex while the same action is being performed under conscious control (Ramnani, 2001; Sakai, 2002). These experiments found that the prefrontal cortex was activated when the actions (finger sequences) were under conscious control, but that it was not significantly active when the actions were performed automatically.

Dopamine in the prefrontal cortex

Dopamine is one of the major neurotransmitters used for communication between the neurons in the brain. Dopamine-sensitive neurons in the cerebral cortex are found primarily in the prefrontal cortex. The dopamine system is associated with cognition, planning, motivation, reward, and pleasure. Poor regulation of dopamine pathways has been associated with schizophrenia. Dopamine controls the flow of information to the prefrontal cortex from other areas of the brain. Dopamine disorders in the prefrontal cortex can cause a decline in cognitive functions, especially memory, attention, and problem-solving.

Reduced dopamine concentration in the prefrontal cortex is thought to contribute to attention deficit hyperactivity disorder (ADHD). A dopamine neurotransmitter released during neural signaling is normally removed from the synaptic cleft and recycled by the transporter. Inhibition of the dopamine transporter increases the level of the dopamine neurotransmitter in the synapse and prolongs dopamine effect on the postsynaptic neuron. Both Ritalin, prescribed for ADHD, and cocaine block the dopamine transporter. In children, Ritalin improves attention and mental synthesis. In adults, the drugs stimulate mental synthesis and amplify sexual interest and pleasure.

Psychotic diseases, such as schizophrenia, bipolar disorder, mania, and delusional disorder have all been linked to a dysfunction of the prefrontal cortex. Anti-psychotic medications, which block dopamine action, are used in the treatment of delusions, auditory hallucinations, and thought disorder in schizophrenia. On the positive side, anti-psychotic medications reduce super-active mental synthesis and therefore alleviate psychotic symptoms such as hallucinations. On the negative side, the reduction of mental synthesis by anti-psychotic medications can interfere with a patient’s intelligence. The Nobel Prize winning American mathematician, John Nash, depicted in the movie “A Beautiful Mind”, famously abstained from anti-psychotic medications because the drug interfered with his intellectual abilities.

Cognitive maturity and the prefrontal cortex

Cognitive maturity is strongly associated with maturation of neuronal connections in the prefrontal cortex. The team headed by Arthur Toga reported increased myelin in the prefrontal cortex of young adults compared to that of teenagers. Myelin electrically insulates axons (the long branches of neurons). This insulation is essential for fast and reliable transmission of signals between neurons. Incomplete myelination of axons may explain the lower ability of teenagers and children to recognize future consequences resulting from current actions, to choose between good and bad actions, and to override and suppress unacceptable social responses: all processes that depend on mental synthesis.

Cellular composition of the prefrontal cortex

The prefrontal cortex is distinguished from other comparable areas of the cortex by a higher number of connections between the neurons, and a considerably lower density of neurons (Jacobs, 2001). A significantly greater number of inputs received by each neuron in the prefrontal cortex indicates that these neurons are involved in integration of more information than the neurons in any other comparable area of the cortex.

Summary of the role of the prefrontal cortex in mental synthesis

In summary, people with a damaged prefrontal cortex are often impaired in their ability to plan complex sequences of actions, suggesting a reduction in the capacity for mental synthesis. After all, the only way to mentally plan an action is by using the process of mental synthesis.

The patients with a damaged prefrontal cortex often act impulsively (as we have seen in the case of Phineas Gage), not being able to predict the consequence of their actions. This observation is again suggestive of the role of the prefrontal cortex in mental synthesis. Without mental synthesis, a person is limited to act upon reflexes, without any planning or foresight. Patients are also unable to solve complex arithmetical problems such as: “A son is 5 years old; in 15 years his father will be twice as old as he. How old is his father now?” This again suggests the role of the prefrontal cortex in mental synthesis, since solving such problems often involves visualization and planning.

Brain imaging in healthy subjects also implicates the prefrontal cortex in tasks that require mental planning and problem solving.

The prefrontal cortex has rich neuronal input from both the alert centers in the brain-stem, and from the limbic regions. If a person’s arousal circuits are silent, which happens when one is in deep sleep or under anesthesia, the person is incapable of mental synthesis. In other words, mental synthesis depends on the active arousal of circuits in the brain stem and thalamus that exercise their control primarily via connections to the prefrontal cortex.

The importance of the prefrontal cortex for higher-order cognitive functions is largely undisputed. However, the mechanism of execution of these functions is fundamentally unclear. The model in which the prefrontal cortex is an organizer of mental synthesis can explain the mechanism of higher-order cognitive functions and lack of these functions in patients with damage to the prefrontal cortex. In the model proposed in this book, the prefrontal cortex is an executive that synchronizes the activity of its employees (neuronal ensembles). Each ensemble of neurons encodes memories of events and objects. The memories are stored throughout the cortex. The prefrontal cortex controls the activation and timing of neuronal ensembles’ activity. By shifting the activity of neuronal ensembles in- and out-of-phase with the attention rhythm, the prefrontal cortex can synthesize new, never-before-seen images and create new conscious experiences. When you thought of a cup standing on a keyboard, the word “cup” registered by the visual system induced the neuronal ensemble encoding a cup to fire synchronously; then the word “keyboard” induced the neuronal ensemble encoding a keyboard to fire synchronously; finally, the frontal lobe synchronized the activity of both ensembles of neurons with the attention rhythm, thus synthesizing a new mental image of a cup on top of a keyboard. Once the two neuronal ensembles were synchronized with each other and with the attention rhythm, they formed a new neuronal ensemble that was stored in memory and could be reactivated at a later time as one unit.