---------- Biological Basis of Behavior ------ ----
---------- SPRING, 2005 ----------

                            
                            
                       BIOLOGICAL BASIS OF BEHAVIOR

Psychology 321                     	                   
Spring, 2005					HGH 225
Dr. John M. Morgan                 	MWF, 8am to 9:00                                                   


Erin Averill 

Prefrontal Cortex-- Neurologists Perspective

Frontal Cortex



	The prefrontal cortex is the most anterior portion of the 
frontal lobe.  It responds mostly to stimuli signaling the need 
for movement, however it is also responsible for many other 
specialized functions.  It receives information from all sensory 
systems and can integrate a large amount of information (Kalat 
2004).

	Studies have shown that the prefrontal cortex is 
responsible for working memory.  Working memory is defined as 
"the information that is currently available in memory for 
working on a problem" (Anderson 2005).  The prefrontal cortex 
(PFC) also controls behaviors that depend on context (Kalat 
2004).  For example, if my cell phone rings when I am at the 
mall or grocery store I would answer it.  If it rings while I am 
at the movies or in class I wouldn't answer it.  People with 
frontal lobe damage often exhibit inappropriate behaviors due to 
the inability to recognize context.

	Other studies indicate that the PFC is also responsible for 
regulating emotions and decision-making.  A study was conducted 
in which participants were presented with three dilemmas.  One 
dilemma was called the Trolley Dilemma: a trolley is headed 
toward five people standing on the track.  You can switch the 
trolley to another track killing only one person instead of 
five.  Subjects were asked to decide between right and wrong.  
Brain scans of the participants show that contemplating the 
dilemmas activates the prefrontal cortex and other areas that 
respond to emotion (Kalat 2004).

	Sustaining a lesion to the prefrontal cortex produces a 
wide variety of side effects.  The effects range from minor to 
severe.  You can get a lesion by head trauma or stroke (CJ Long 
2005).  

Possible deficits associated with minor lesions of the 
prefrontal cortex:
?	Inability to respond quickly to verbal instructions
?	Speech dysfluency
?	Disturbances in understanding complex pictures or words
?	Difficulties with problem-solving
?	Deficits in complex tasks requiring inhibition of habitual 
behavior patterns

	With more extensive lesions the person experiences greater 
behavior deficits.  These deficits include: perseveration, which 
is the inability to make behavioral shifts in attention, 
movement and attitude, decreased creativity, poor recall of 
verbal and nonverbal material, difficulty writing, and deficits 
in comprehension of logical-grammatical constructions (CJ Long 
2005).

Other effects of extensive lesions:
?	easily distracted
?	disturbances in memory
?	defects in time sense
?	decreased anxiety 
?	less critical of oneself
?	difficulty with unfamiliar analogies
?	impulsivity
?	emotional disturbances such as: apathy, withdrawal, euphoria, 
irritability, and obscene language.

	Mah, Arnold, and Grafman (2004) conducted a study about the 
impairment of social perception associated with lesions of the 
prefrontal cortex.  They used the Interpersonal Perception Task, 
which consisted of several videotapes of social interaction.  
For each social interaction participants were asked to judge 
different aspects of behavior such as level of intimacy and 
social status (Mah, Arnold, and Grafman 2004).  The results of 
the judgments were compared between participants with prefrontal 
lesions and healthy participants.  The results showed that 
participants with prefrontal lesions showed poorer performance 
on the Interpersonal Perception Task than the healthy 
individuals.  This means that participants with prefrontal 
cortex lesions were less able to interpret social behavior thus 
implying other cognitive deficits.

	This study also found a strong correlation between 
performance on the Interpersonal Perception Task and other 
cognitive deficits, including deficits in working memory and 
executive function.  These deficits also affect decision-making 
ability, which explains why subjects were having difficulty 
interpreting social situations (Mah, Arnold, and Grafman 2004).  

	The results from this experiment also show deficits in 
theory of mind.  Theory of mind is the "ability to attribute 
mental states to self and others" (Mah, Arnold, and Grafman 
2004).  The task required participants to use nonverbal cues to 
pass judgments about the type of relationships shown between 
individuals.  This requires "accurate perception of social cues 
as well as perspective-taking," which this experiment has shown 
that people with prefrontal cortex lesions have trouble doing.

	Impaired social perception contributes to inappropriate 
responses in subjects with prefrontal lobe damage.  Damage in 
this brain region may also be involved in deficits in perception 
of emotional cues, interpersonal judgments, and self-awareness 
of cognitive ability (Mah, Arnold, Grafman 2004).

	There have been several case studies done on the effects of 
prefrontal lesions on children and how it affects their 
development.  Ackerly and Benton (1948) did a study on JP, which 
is one of the most informative cases available.  He had 
extensive prefrontal lobe damage with a congenital onset. 
However, JP seemed to be developing normally, he learned to walk 
and talk by age 1.  His family didn't notice a problem until he 
was 3 years old when he began to wander long distances without 
fear.   He also had problems in school.  He was boastful, bossy, 
and stole money from other kids.  He also had impairments in 
inhibition, attention, working memory, delay of responding, 
which are all typical characteristics of prefrontal cortex 
damage.  Because of his poor social adjustment he was extremely 
disliked in school.  The authors of the study determined his 
primary social defect as an "immature level of differentiation 
and elaboration of the cognitive and affective processes that 
underlie role-taking, theory of mind, cooperation, and self-
evaluation" (Benton, Eslinger, Flaherty-Craig 2003).

	Eslinger studied DT, who experienced a left frontal lesion 
at age seven.  She developed pronounced social impairment 
including social alienation and uncooperative behaviors.  She 
was argumentative, did not share, and showed little concern for 
others.  In school she had poor attention control, trouble 
learning, and was disorganized.  Her social ineptness carried on 
throughout her life.  As an adult she continued to show 
immature, impulsive and erratic behaviors.  She could not 
regulate her emotions and could not anticipate the needs of 
others.  She managed to get married and have a child, however 
her extreme deficits seriously compromised her ability as a 
mother and wife.  She could not hold down a job due to 
disorganization and lack of commitment.  She ranked lower than 
average in intelligence, working memory, executive function, and 
problem-solving.  Her moral development was also around that of 
a 10-13 year old.  Her poor regulation of emotion, lack of 
empathy, argumentativeness, and disregard for social boundaries 
led to severe social problems.

	Among all the case studies reviewed in the article 
Developmental Outcomes After Early Prefrontal Cortex Damage, the 
authors noted several distinct characteristics present among all 
the patients:
?	impaired social cognition- uncooperative, limited perspective 
taking skills
?	learning deficits 
?	impaired cognition - decreased intellectual capacities
?	deficits in personality and emotion - impatience, 
irritability, egocentric, and labile moods
?	deficits in moral behavior and empathy 

	The above mentioned deficits are consistent effects 
reported for patients with lesions to the prefrontal cortex.



References

Anderson, John R. (2005) Cognitive Psychology and its 
Implications. Worth Publishers: New York.

Eslinger, Paul J., Flaherty-Craig, Claire V., Benton, Arthur 
L. (2004). Developmental outcomes after early 	prefrontal 
cortex damage. Brain and Cognition, 55, 84-	103.

Kalat, James W. (2004) Biological Psychology. Ontario, Canada: 
Wadsworth.

Long, C.J. Brain-Behavior Relationships: Prefrontal Cortex.
http://neuro.psyc.memphis.edu/NeuroPsyc/np-12-pref.htm.

Mah, Linda, Arnold, Miriam C., Grafman, Jordan. Impairment of 
social perception associated with lesions of the 	prefrontal 
cortex. American Journal of Psychiatry, 161, 	1247-1255.




Holly Young
Psyc 321
Prefrontal Cortex Lesions from Neurosurgeon and Patient 
Perspective
       									
       In this section of the paper, I will discuss lesions of the 
prefrontal cortex from the perspective of the practice of 
neurosurgery (in particular, the sub-field of psychosurgery) and 
then I will consider some studies that look at the implications 
of lesions to the prefrontal cortex to the brain and behavior, 
from the perspective of the patient with the lesion. Initially, 
I will start with the history and explanation of psychosurgery. 
Psychosurgery is the branch of neurosurgery that involves 
severing or otherwise disabling areas of the brain to treat a 
personality disorder, behavior disorder, or other mental illness 
(Rodgers 1992). Modern psychosurgical techniques target the 
pathways between the limbic system (the portion of the brain on 
the inner edge of the cerebral cortex) that is believed to 
regulate emotions, and the frontal cortex, where thought 
processes are seated.				
       The field of neurosurgery as a specialty was not defined 
until the end of the 19th century. In earlier days, surgeries 
had to be tailored to poor lighting and lack of magnification 
(Valenstein 1986). The development and implementation of the 
operating microscope in the 1960s allowed surgeons to operate 
through a narrow tunnel to resect deep-seated lesions 
(Valenstein 1986). Psychosurgery, and lobotomy in particular, 
reached the height of use just after World War II. Between 1946 
and 1949, the use of the lobotomy grew from 500 to 5,000 annual 
procedures in the United States (Valenstein 1986). Lobotomy is a 
psychosurgical procedure involving selective destruction of 
connective nerve fibers or tissue. It is performed on the 
frontal lobe of the brain and its purpose is to alleviate mental 
illness and chronic pain symptoms (Valenstein 1986). At that 
time, the procedure was viewed as a possible solution to the 
overcrowded and understaffed conditions in state-run mental 
hospitals and asylums. Known as prefrontal or transorbital 
lobotomy, depending on the surgical technique used and area of 
the brain targeted, these early operations were performed with 
surgical knives, electrodes, suction, or ice picks, to cut or 
sweep out portions of the frontal lobe.			
       Today's psychosurgical techniques are much more refined. 
These technological advances include the use of computer-
assisted stereotaxis, intra-operative ultrasound, brain mapping 
and endoscopy. Minimally invasive surgery is a major advance in 
neurosurgery and refers not only to a more limited skin incision 
with precise centering of a burr-hole or small craniotomy 
directly over the brain lesion, but also to the planning of a 
precise trajectory to the lesion that will not injure adjacent 
brain (“Minimally” 2005). The least invasive treatment option 
available to neurosurgeons is radiosurgery, which combines 
radiotherapy techniques with sophisticated computer-assisted 
stereotaxis.   
       Instead of going in "blind" to remove large sections on the 
frontal lobe, as in the early operations, neurosurgeons use a 
computer-based process called stereotactic magnetic resonance 
imaging to guide a small electrode to the limbic system (brain 
structures involved in autonomic or automatic body functions and 
some emotion and behavior) (Spangler 1996). There an electrical 
current burns in a small lesion (usually 1/2 inch in size). In a 
bilateral cingulotomy, the cingulate gyrus, a small section of 
brain that connects the limbic region of the brain with the 
frontal lobes, is targeted. Another surgical technique uses a 
non-invasive tool known as a gamma knife to focus beams of 
radiation at the brain (Spangler 1996). A lesion forms at the 
spot where the beams converge in the brain.				
       Psychosurgery is considered only after all other non-
surgical psychiatric therapies have been fully explored. Much is 
still unknown about the biology of the brain and how 
psychosurgery affects brain function; therefore, candidates for 
psychosurgery undergo a rigorous screening process to ensure 
that all possible non-surgical psychiatric treatment options 
have been explored (Rodgers 1992). Psychosurgery is performed 
only with the patient's informed consent. As with any type of 
brain surgery, psychosurgery carries the risk of permanent brain 
damage, though the advent of non-invasive neurosurgical 
techniques, such as the gamma knife, has reduced the risk of 
brain damage significantly. 				
       A neurosurgeon might lesion an area of the prefrontal 
cortex, either to fix a brain deficit or accidentally cause a 
deficit; there are numerous deficits that can result from 
prefrontal lesions. The prefrontal cortex is responsible for 
“executive functions;” planning, structuring, and evaluating 
voluntary goal directed behavior, which are activities requiring 
the constant comparison of planned acts with the effects 
achieved. It is a region of the cerebral cortex thought to be 
unique to primates; the same area in rats, for example, is 
thought to be used for generating movements and processing the 
emotions and rewards associated with them (Rainer 2001). In 
humans, the prefrontal cortex is composed of a number of highly 
interconnected frontal lobe areas (Wood 2003). At the coarsest 
level, researchers have differentiated between dorsolateral, 
ventrolateral, orbitofrontal, and anterior prefrontal cortex. 
Although it is unclear what precise functions these regions 
implement, it is clear that these regions typically work in 
concert to enable goal-directed behavior. The orbitofrontal 
cortex lies just on top of the eyes, and seems to have a role in 
adding an emotional element to planning and decisions. The 
ventrolateral prefrontal cortex lies on the side of the front 
bit of the forehead, and is important in working memory. The 
dorsolateral prefrontal cortex is important in decision making, 
and particularly in switching and maintaining 'attentional set' 
(Wood 2003). Pre-frontal neurons participate in a variety of 
functions, including motor planning (Manes 2003) and the 
processing of auditory (Manes 2003) and somatosensory (Manes 
2003) stimuli. The pre-frontal cortex also contains many neurons 
that respond selectively to complex objects (Wood 2003).     	
       One of the main functions of the prefrontal cortex 
presented through the literature is in working memory. The role 
of working memory seems to be in guiding and adapting behavior 
through its ability to hold information (Bechara 1998). This has 
been demonstrated through the impaired performance of monkeys 
with prefrontal damage on delayed matching to sample, and 
delayed non-matching to sample tasks (Passingham, 1998). Such 
inability to adapt and change behavior is also seen in humans 
with prefrontal lesions. (A lesion is any discontinuity of 
tissue, often a cut or wound) (Rodgers 1992). Patients with 
frontal lesions tend to be absent-minded and very easily 
distracted (Shallice 1991). They do not seem to organize and 
plan actions very well. For instance, patients have been known 
to be completely unable to do shopping efficiently. They might 
go into the shop, purchase just one item, return to their car, 
re-enter the shop, buy one more item, return to their car, and 
so forth (Shallice 1991). Difficulties in such "multiple sub-
goal tasks" are fairly common among frontal patients. Patients 
with frontal lesions also tend to display behavioral responses 
inappropriate to the situation and this can be clearly seen in 
the Wisconsin Card Sort Test (where cards have to be sorted 
according to color, shape, or number, depending on whether the 
experimenter says "right" or "wrong"). Using this apparatus, 
Milner (1963) observed that patients with frontal lesions had 
difficulty in figuring out the first sorting principle, and 
furthermore, were impaired in the ability to shift to a second 
sorting principle when required. Shallice and Burgess (1991) 
account for problems in the performance of multiple sub-goal 
tasks by the lack of a "supervisory system" controlling 
processes such as goal articulation, plan formulation, and the 
creation and triggering of markers (a message that some future 
behavior or event is significant to current goals). Rolls (1998) 
attributes the problems in performing the Wisconsin Card Sort 
Test, not to working memory problems, but rather to problems in 
altering behavior to changes in stimulus-reinforcement 
associations. Rolls suggests that the "orbitofrontal cortex is 
involved in emotional responses by correcting stimulus-
reinforcement responses when they become inappropriate". 		
				I will not detail emotional deficits 
associated with prefrontal damage in this paper, but I will 
state briefly that emotional disturbances fall under two 
principle reactions: inhibition (apathy, narrowing of interests, 
flattered affect, withdrawal) and disinhibition (euphoria, 
impulsivity, irritability, anxiety, obscene language (Luria 
1969). Decreased spontaneity, decreased rate of behavior, 
decreased range of interests, loss of initiative, and 
impulsiveness without self-corrective action may be early signs 
of a lesion (Davidson 1977). These disturbances are often 
related to decision making, which is another function that has 
been attributed to the prefrontal cortex. A study by Bechara et 
al. (1998) confirms that this process is located in the 
prefrontal region, and in addition, that decision making is a 
distinct process from the working memory processes that are 
known to exist in prefrontal cortex. The experimenters tested 
patients with various frontal lesions with delay tasks that 
assessed working memory and with a gambling task that assessed 
decision making. It was found that among the subjects with 
ventromedial prefrontal lesions, those with more anterior 
lesions had an impaired performance on the gambling, but not the 
delay task, whereas those with more posterior lesions were 
impaired on both tasks. Among the patients with 
dorsolateral/high mesial lesions, those with right hemisphere 
lesions were impaired on the delay task, but not the gambling 
one, whereas those with left hemisphere lesions displayed no 
impairment of either task. This experiment successfully 
demonstrated a cognitive and anatomical double dissociation 
between decision making deficits (localized in anterior 
ventromedial prefrontal cortex) and working memory (localized in 
right dorsolateral/high mesial prefrontal cortex). The authors 
suggest that the decision making impairment, caused by anterior 
vetromedial lesions, is linked to "insensitivity to future 
consequences" (1998). In other words, such patients seem 
oblivious to the future and instead are guided by immediate 
prospects, whether they are positive or not. They specifically 
do not link their results to an explanation by failure to 
inhibit previously rewarded responses (perhaps suggesting that 
Rolls' stimulus-reinforcement ideas are confined to 
orbitofrontal cortex). Nor do they agree with the view that 
there is an impairment in selective attention in that subjects 
are unable to shift their attention to a new and beneficial 
objects in the gambling task.		In another interesting 
experiment, done by Milne and Grafman (2001), patients with 
prefrontal cortex lesions and controls were administered an 
implicit association task (IAT) that measured the degree of 
association between male and female names and their 
stereotypical attributes of strength and weakness. They also 
completed three questionnaires measuring their explicit judgment 
regarding gender-related stereotypical attributes (Milne 2001). 
There were no between-group differences on the explicit 
measures. On the IAT, patients with dorsolateral lesions and 
controls showed a strong association, whereas patients with 
ventromedial prefrontal cortex lesions had a significantly lower 
association, between the stereotypical attributes of men and 
women and their concepts of gender (Milne 2001). This finding 
provides support for the hypothesis that patients with 
ventromedial prefrontal lesions have a deficit in automatically 
accessing certain aspects of overlearned associated social 
knowledge (Milne 2001).		
       After ventromedial frontal lobe brain injury, patients 
often demonstrate acquired social conduct deficits such as an 
inability to respond appropriately to social cues in the 
environment or failure to obey conventional social rules (Milne 
2001). These deficits may be accompanied by a lack of awareness 
of what is socially appropriate (Milne 2001). Because of these 
deficits, the ventromedial sectors of the prefrontal cortex have 
been considered the repository of social knowledge of the brain 
that is required for managing interpersonal interactions 
(Grafman, 1994, 1995). If this knowledge becomes inaccessible or 
degraded, behavior may default to inappropriate social rules for 
the situation or be guided by more instinctive or primitive 
responses induced by the environment (Grafman, 1994, 1995).
       Evidence from previous studies has suggested that despite 
their aberrant real-life behavior, some patients with 
ventromedial frontal lobe lesions do possess, and can access, 
the social knowledge that they appear not to use in everyday 
life. For example, patient E.V.R.-- cited because of a striking 
dissociation between his preserved language, memory, and 
intellectual skills and his profoundly impaired social conduct, 
which developed after bilateral excision of orbital and lower 
mesial cortices-has been tested on several explicit measures of 
social cognition requiring means end problem solving of social 
situations and prediction of social solutions and was found to 
perform at levels equivalent or superior to normal controls 
(Milne 2001). One explanation for his impaired social decision 
making is that ventromedial frontal lobe lesions result in a 
somatic marking deficit (Damasio 1998). Somatic marking is a 
hypothesized mechanism that binds a positive or negative valence 
to a behavioral action that facilitates the decision of what is 
the correct or appropriate response in a given social situation.
       On the other hand, Dimitrov et al. (1998) have demonstrated 
that unlike E.V.R., some patients with ventromedial lesions 
display impaired social knowledge compared with matched controls 
on an inventory designed to measure a person's understanding of 
the relative effectiveness of various solutions to everyday 
social problems (Dimitrov et al., 1999). To further investigate 
the cause of the social conduct disorder frequently observed in 
patients with prefrontal cortex lesions, Milne and Grafman 
(2001) adapted a task from the social cognition literature that 
addresses the nature and organization of stored social 
knowledge. The implicit association task (IAT) is used to 
measure the automatic concept-attribute associations that are 
hypothesized to underlie implicit social attitudes and 
stereotypes (Milne 2001). Normal subjects typically demonstrate 
relatively faster reaction times when they are asked to map 
stereotypically compatible (compared with incompatible) concepts 
onto a single response (known as the IAT effect). Scores on this 
implicit measure are often weakly (if at all) associated with 
explicit scores based on probing of attitudes or stereotypes 
(Milne 2001). Stereotypes can be considered a form of social 
knowledge
       Patients with ventromedial prefrontal cortex lesions showed 
impaired automatic priming of stereotypic social knowledge, 
whereas those with dorsolateral prefrontal cortex lesions 
performed like normal subjects. Social bias, such as a gender 
stereotype, represents social knowledge that is acquired during 
development. The content of the stereotype is dependent on 
cultural factors and the environmental influences to which an 
individual is subjected. Stereotypes reflect an economy of 
thought (Milne 2001), an attempt to organize the world around us 
into groups and categories that have certain perceived 
attributes (2001). Despite the small number of subjects examined 
the Milne (2001) study, the results indicate that patients who 
suffered ventromedial prefrontal cortex lesions have a degraded 
representation of social knowledge that can be demonstrated 
through priming experiments.


       
       References: 

Bechara et al. (1998), Dissociation of working memory from 
decision making within the human prefrontal cortex, Journal of 
Neuroscience 18, 428-37 

Damasio AR  (1995) On some functions of the human prefrontal 
cortex. Ann NY Acad Science    769:241-251.
	
Damasio AR  (1998) Emotion in the perspective of an integrated 
nervous system. Brain Res  Brain Res Rev 26:83-86	

Davidson, L.A. (1977). Syndromes of deficits by area of maximal 
cortical damage. In Reitan, R.M. and Davison, L.A., 
Neuropsychological Procedures and Methods, unpublished manual.

Dimitrov M, Grafman J, Hollnagel C  (1996) The effects of 
frontal 
lobe damage on everyday problem solving. Cortex 32:357-366.

Dimitrov M, Phipps M, Zahn TP, Grafman J  (1999) A thoroughly 
modern gage. Neurocase 5:345-354

Grafman J  (1994) Alternative frameworks for the 
conceptualization of prefrontal lobe functions. Handbook of 
neuropsychology (Boller F, Grafman J,  eds): 187-202. Amsterdam: 
Elsevier.

Grafman J  (1995) Similarities and distinctions among current 
models of prefrontal cortical functions. Ann NY Acad Sci 
769:337-368.

Luria, A.R. (1969). Frontal lobe syndromes. In P.J. Vinken and 
G.W. Bruyn (Eds.), Handbook of Clinical Neurology II. New York: 
Elsevier.

Manes, F. Sahakian, B. Clark, L. Rogers, R. Antoun, N. Aitken, 
M. & Robbins, T. (2002). Decision-making processes following 
damage to the prefrontal cortex. Brain, 125, No. 3: 624-639.

Milner, B. (1963). The effects of different brain lesions on 
card 
sorting. Archaeological Neurology 9, 90-100. 

Milne E. & Grafman J. (2001). Ventromedial Prefrontal Cortex 
Lesions in Humans Eliminate Implicit Gender Stereotyping. The 
Journal of Neuroscience, (21): RC150:1-6

“Minimally Invasive Neurosurgery”: Department of Neurosurgery, 
Singapore General Hospital. Retrieved from 
http://www.sgh.com.sg/MedicalSpecialtiesnServices/ClinicalS
ecialties/Surgical/Neurosurgery/MinimallyInvasiveNeurosurge
y/  (28 April 2005).

Passingham, R.E. (1998), Attention to action. The Prefrontal 
Cortex, Eds. Roberts, Robbins, Weiskrantz, OUP, Oxford. 

Rainer, G. & Ranganath C.  (2001). Coding of Objects in the 
Prefrontal Cortex in Monkeys and Humans. Neuroscientist. 
8(1):6-11.

Rao, S.C., Rainer, G., Miller, E.K. (1997). Integration of what 
and where in the primate prefrontal cortex, Science 1997 May 2: 
276, 821-4 

Rodgers, J.E. (1992). Psychosurgery: Damaging the Brain to Save 
the Mind. New York: HarperCollins. 

Rolls, E.T. (1998), The orbitofrontal cortex, in; The Prefrontal 
Cortex, Eds. Roberts, Robbins, Weiskrantz, OUP, Oxford. 

Shallice, T., and Burgess, P.W. (1991). Deficits in strategy 
application following frontal-lobe damage in man, Brain 114, 
727-41

Valenstein, Elliot S. (1986). Great and Desperate Cures: The 
Rise and Decline of Psychosurgery and Other Radical Treatments 
for Mental Illness. New York: Basic Books.

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Stereotactic Cingulotomy for Intractable Psychiatric Disease." 
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Nature Reviews, 4, 139-147. www.nature.com/reviews/neuro. 




Neuropsychologist
Eric Wilcox
Lesions to the Prefrontal Cortex
Basic anatomy

The prefrontal cortex is the last part of the brain to mature, 
it is considered the latest development in evolution, and it is 
characteristic of the highest thinking animals.  In humans, the 
prefrontal cortex matures in the late teens and early twenties.  
Aspects of memory dependent upon the prefrontal cortex improve 
at maturation.  Increase in white matter occurs while the number 
of neurons decrease in a process called aptosis.  This is the 
maturation of the cortex, the successful connections of neurons, 
and the death of neurons that fail to connect. Children have a
better chance of recovery from lesions than do adults.

There are fundamental differences between the limbic and 
eulaminate cortices of the prefrontal cortex.  The limbic 
cortices have three distinguishable layers, more rarely four.  
The eulaminate areas have six layers.  The differences in these 
areas are their behavioral and physiological aspects.

Projections from the thalamus extend to the prefrontal cortex.  
The thalamus makes connections with all the cerebral cortex, and 
sends signal from the sensory peripheral to the respective 
sensory cortices. Thalamic input, though, is thought to 
contribute to cognitive, mnemonic, and emotional function in the 
prefrontal cortex.  The eulaminate areas receive less than half 
the projections, whereas the limbic cortices receive more 
projections.

The hippocampus and amygdala are two limbic structures that 
project tracts into the medial limbic and orbitofrontal cortices 
of the prefrontal cortex targeting the limbic cortices heavily.  
In general, limbic cortices are more heavily connected with 
other limbic cortices, as in the occipital, temporal, and 
parietal cortices, which have more modalities than the
eulaminate connections.  This is in part the description of the 
executive function of the prefrontal cortex, for it connects 
with many parts of the brain, and is executive in the planning 
with this communication, as well as many other functions.

Lesions and Effects: On Attention and Perception

Depending upon the location of the lesion in the prefrontal 
cortex, there are three categories of disordered functions in 
the behavioral sphere, the cognitive sphere, and the affective 
sphere.

The most common cognitive disorder comes from abnormalities of 
attention.  When damage occurs to the dorsolateral prefrontal 
convexity there is dysfunction with low alertness and low 
awareness to the world around the patient.  There is little 
interest in the environment or the motives and activities of 
other people.  There is less participation in society. 
There seems to be a basic lack of drive.  So, they are less 
spontaneous in their actions.  The low arousal could be 
responsible for attention difficulties.  Sensory neglect is a 
more specific form of attention deficit which is a lack of 
awareness on one side of the body contralateral of a unilateral 
prefrontal lesion.  Neglect also has to do with not attending to 
half the field of vision.

Distractibility may occur from orbitalfrontal lesions where the 
person is unable to resist interference from stimuli.

Disorder of visual search and gaze control is the loss of 
normal, logical order in the analysis of pictorial detail.  
Visual examination is haphazard and unsystematic.  The person 
may gaze at the expense of gathering pertinent details.

The most consistent trait of these disorders is the difficulty 
in sustaining attention.  The greater the duration and 
complexity of a mental operation, the more evident is the 
deficit.

Internal interference results from impulses that interfere with 
attention. To test function, the Wisconsin Card Sorting Test 
(WCST) uses four “target cards” face up, each with a different 
printed design, number of designs, and color.  The subsequent 
cards are to be placed according to the category principles.  
After reaching ten correct choices, the clinician creates new 
category principles. The patient must discard the
old principles and discover the new; they must keep the shift in 
mind. Poor performance can show internal interference and that 
this may be responsible for poor short-term memory tasks.
Tower of London


On Motility

Defective motor attention (set) may be disrupted.  This can be 
seen in motor tasks that are liable to internal interference 
from impulses that need to be inhibited or suppressed.  Although 
lesions in the prefrontal cortex are not located near the 
premotor or motor cortex, disorders of motility can occur.  
Disorders come in two forms; general spontaneous, and goal-
directed motor behavior.  Hypokinesia seems logical in its 
association with apathy and lack of initiative, and reactivity 
to stimuli involved with attention dysfunction.  Degrees in 
severity range from “aspontaneity” which affects language and 
social behavior, to akinetic-abulic syndrome with mutism.  These 
can result from lesions to the dorsolateral, as well as the 
orbitomedial areas (Fuster,1997 p.155).

Hyperkenisia is excessive motility and is common with 
orbitofrontal lesions.  Hyperactivity, instinctual 
disinhibition, distractibility, hypomania, and irritability are 
some other symptoms.

With goal-driven motor behaviors, motility disorders are more a 
result of cognitive dysfunction which impedes the initiative and 
temporal organization of action.

People show few deliberate acts, and lack initiative whether it 
comes from general motility or goal-directed motility.  However, 
the patient may show an increase in automatic behaviors.  
Repetitious patterns in routine behaviors are resorted to in 
what is called perseveration.  When faced with seemingly 
insurmountable cognitive tasks, the patient regresses to routine 
behavior in an attempt to solve the problem, and may seem 
superstitious.

Long-term memory seems not to be affected, while recent memory 
is.  This is attributed to the low perceptual attention and low 
motivation.  In essence the person forgets to remember.  Also, 
there is impairment to the working short-term memory, or 
provisional memory.  This is needed for all planning of actions, 
mental, motor, or language.  There are batteries of tests for 
this function.  Delay task tests, and the Wisconsin Card Sorting
Task are just a couple of them, and that we as 
neuropsychologists need to know how to apply them.

The WCST tests short-term memory and the ability to withstand 
interference from unimportant memories.  Lesions to the 
dorsolateral and orbitomedial regions affect performance.  
However, people with lesions in some
nonfrontal areas perform poorly, as well.  There is some 
question to the WCST’s validity for testing prefrontal patients.  
There are difficulties in controlling for attention or deficit 
factors, and attributing memory deficit to interference.  
Frontal lesions can impair suppression of interference as well 
as memory.  Testing is difficult.

Planning

Faulty short-term memory affects a person’s ability to use their
experience of the recent past, whereas faulty foresight impairs 
the ability to plan for the future.  These two deficits are a 
“mirror image” of each other, one being retrospective, the other 
is prospective.  A lesion to the dorsolateral prefrontal 
convexity produces deficits in both. The inability to plan is 
the most consistently recorded dysfunction. 
Unlike the memory deficit, which arouses controversy, the 
deficit in prospective memory is strictly associated with the 
prefrontal cortex.

This is also known as executive function, and it depends upon 
the ability to plan.  To test this, one test called the Tower of 
London consists of three wooden pegs, and three wooden rings of 
different colors. One peg holds three rings, the second can hold 
two, the third, one. The rings are placed one on each peg to 
start.  The patient must move the rings to a desired 
configuration in a minimal amount of moves.  This test requires 
planning a series of sub-goals to reach the final goal.  This 
requires anticipation and visualization of the goal, and to 
internally arrange the proper sequence.  Lesions to the left 
hemisphere perform poorly.  Maze tests prove difficult as well, 
probably due to poor planning.

Intelligence

It has been argued that evolution has developed the frontal lobe 
last and is characteristic of the higher intelligent animals.  
However, people have tested normal to above average on I.Q. 
tests with prefrontal lesions.  Logic dictates that deficits in 
verbal expression, memory, abstraction, and the ability to 
formulate behavioral plans and to pursue them to their goal 
(Fuster, 1997 p.163), are components of intelligence needed for 
temporal integration of behavior which is complex, original, and 
creative. Therefore, a couple of I.Q. tests should be able to 
determine frontal lobe damage.  The Weschsler Adult Intelligence 
Test is more sensitive than the Stanford-Binet Test, especially 
with left lobe damage.  The Spearman’s G Test tests fluid 
intelligence, or the capacity to solve new problems, and is also 
sensitive to goal neglect.

Language
Broca’s area


Language is a form of sequential behavior based on the exercise 
of temporal function, and the cognitive functions that support 
it (Fuster, 1997 p.166).  Temporal integration is similar to 
executive function in organizing temporally separate items, 
except it does not need a central executive.  The most well 
known disorder is Broca’s aphagia, this is slow and effortful 
speech lacking fluidity and continuity.  Lesions to Broadman’s 
area 44 and 45 produce this effect.  Broca’s area is responsible 
for the most elementary combination of morphemes, which are the 
simplest units of language.  The most anterior prefrontal cortex 
mediates the elaborate structures of spoken language.  For 
prefrontals, difficulty exists in accessing verbs over nouns, as 
well.

Emotions and Affect

Apathy, depression, and euphoria are associated with lesions.  
Apathy results from extensive lesions to the prefrontal 
convexity, and the medial area, as well as blunting of affect.  
Depression results in damage to the anterior frontal lobe 
(left), but depression could be secondary to awareness of loss 
of cognition.  Those who have achieved intellectual achievement 
may be vulnerable, as well as those with family history. 
Euphoria occurs from lesions to the orbital prefrontal cortex, 
occurring sporadically, and resembling hypomania with 
nervousness, irritability, and some paranoia.  It is accompanied 
by a childish, compulsive, shallow humor called moria, or 
Witzelsucht.

Social and Emotional Behavior

Apathy and depression will adversely affect social contact with 
isolation. On the other hand, euphoria can result in 
disinhibition of instinctual drives, a loosening of moral 
restraints, and a loss of capacity to gauge the effects of one’s 
own behavior.  This is similar to criminal sociopathy.

References:
Fuster, Joaquin, M.(1997). Human Neuropsychology.(3rd Ed.), The 
Prefrontal Cortex Anatomy, Physiology, and Neuropsychology of 
the Frontal Love.(pp.150-184). Philadelphia, NY: Lippincott-
Raven.

Levin, Harry, S. & Grafman, J.(2000).  Neuroanatomic Basis for
Reorganization of Function After Prefrontal Damage in Primates.  
(1st Ed). Cerebral Reorganization of Function After Brain Damage 
(pp. 84-90). Oxford, NY: Oxford Press.

Kalat, James, W. (2004).  Development of the Brain. (8th Ed.)  
Biological
Psychology (pp. 111).  Belmont, Ca: Thomas Learning, Inc.

Ruth, Ronald, M. and Barth, Jeffrey, T.(2000). Behavioral 
Neuropsychology
Executive Function.  Retrieved April 20, 2004 from Google:
http://nanonline.org/nandistance/mtbi/ClinNeuro/
executive.html




Shawnee Thayer
Psych 321
Lesions of the Prefrontal Cortex-
Perspective of a family member and employer

       The prefrontal cortex is involved in a wide variety of 
functions.  It is known as the area of the brain which has 
“executive control”, taking input from other areas of the brain 
and combining and applying those functions (Kalat 2004).  
Lesions to the prefrontal area can greatly impair overt behavior 
of an inflicted individual.  These deficits are dependent upon 
the severity of the lesion and the specific region of the 
prefrontal cortex in which the lesion resides (ventrolateral, 
dorsolateral,  orbitofrontal, and anterior prefrontal)(Eslinger 
2003).
       
       Individuals with prefrontal lesions usually display 
emotional, social and moral deficits (Elinger 2003).  Social 
learning is impaired and adaptive learning does not appear to 
extend beyond avoidance of punishment in most cases(Anderson 
1999).  Personality is marked by poor judgment, minimal insight 
into/slight anticipation of consequence, a desire for autonomy 
but a lack of self- initiation, lack of sense of competency, 
lack of identity, a lack of relationship between self and others 
and self and environment, and a deficit in motivation and goal 
directed behavior(Eslinger 2003).  Most cases do not appear to 
experience anxiety or fear.  These persons tend to be 
egocentric, easily irritated, impatient, and display “shallow” 
emotions(Trauner 2001).  They cannot harness their emotions to 
use in an adaptive manner regarding learning from experience, 
and developing and maintaining relationships.  Empathy, moral 
decision making and comprehension are usually erratically rule-
based and self-serving.  There is an inability to demonstrate 
perspective taking and limited to no perception of social cues 
and rules(Mah 2004).  
       
       People who suffer right hemisphere strokes can develop 
difficulty comprehending or expressing emotional cues, such as 
facial expressions, gestures, vocal intonation, and may be 
indifferent to their disability (Trauner 2001).  Persons with 
left hemisphere lesions are often depressed and display 
inhibition which includes apathy, flattened affect, withdrawal, 
narrowing of interests(Trauner 2001).  Patients with right or 
left hemispheric lesions may experience disinhibition which 
includes euphoria, impulsivity, and irritability, inappropriate 
emotional responses and impaired judgment (Trauner 2001).
        
	Intellectual capacities can remain preserved, and 
individuals with prefrontal damage can score normal-average 
intelligence on standard IQ tests (Eslinger 2003).  Cognitive 
deficits which do appear relate to attention, self-regulation, 
inhibition, planning, problem solving, critical thinking, 
organization, working memory, self-awareness and self-
monitoring, and goal-directed behavior (Eslinger 2003).  

       Available cases of early prefrontal cortex damage provide 
evidence for the importance of this region in psychological 
development (Eslinger 2003).  Anderson (1999) discussed the 
important cognitive and behavioral deficit differences between 
childhood onset of prefrontal cortex lesions and adult onset 
lesions to the prefrontal cortex.  Adults who experience a 
lesion to the prefrontal cortex have had years of normal 
cognitive and social behavior development.  A lesion to certain 
regions of the prefrontal cortex will cause severe damage in 
decision making abilities and social behavior, but patients tend 
to retain intellectual abilities and preserve factual social 
knowledge of relevant social conventions, rules and cues, even 
if they find themselves unable to act on them (Anderson 1999).  
       
       Individuals with childhood-onset lesions show a degree of 
cognitive alteration, ranging from moderate to severe (Trauner 
2001).  A child who has a lesion to the prefrontal cortex may be 
unable to obtain the needed decision making abilities and social 
knowledge because the region of the brain which helps them to 
process that information is damaged (Anderson 1999).  Because 
damage to the prefrontal area impairs the ability for a person 
to learn from experience, many children afflicted have developed 
behavioral deficits despite a stable home life, family and 
school peers to model appropriate behavior and behavior 
modification programs aimed at correcting the “problem” behavior 
in childhood and adolescence(Anderon 1999).
       
       The behavioral deficits experienced by adult-onset and 
child-onset prefrontal lesion patients appear similar, but 
child-onset deficits are more severe.  These individuals have a 
greater tendency to display antisocial behavior like stealing 
and violence (Anderson 1999).  Without the years of socially 
relevant knowledge to recall, child-onset patients are less 
likely to experience any form of remorse. Adult-onset behavior 
is more constrained, although acting impulsively and the 
susceptibility to act on immediate cues leaves them at risk to 
harm others (Anderson 1999).  
       
       Two “case histories” of fictional characters will 
illustrate the behavioral deficits experienced by individuals 
with prefrontal cortex lesions.  The first history is told from 
the perspective of a female sibling of a 15 year old female who 
has a childhood onset prefrontal cortex lesion.  The second 
“case history” is told from the perspective of a social worker 
who works with a 44 year old male with an adult onset prefrontal 
cortex lesion.  All the behaviors described follow closely 
actual case histories of individuals with prefrontal lesions 
found in research literature.

Case History #1

       “CC is my 15 year old sister.  When she was 15 months old 
she was run over by a car but everyone thought she was ok.  When 
she was a toddler our parents had her checked out by doctors 
because no matter how much they punished her, she didn’t seem to 
care.  When she was in middle school she was way unpopular.  She 
didn’t ever pay attention in class and would talk back to the 
teacher when she was told to do something so she got in trouble 
a lot.  She would interrupt kid’s conversations a lot and 
sometimes she would get too close to people when she talked.  
When she got mad she would throw a tantrum.  A few times when 
she got mad she hit someone or broke something of theirs but she 
was never sorry. She didn’t care.  She was selfish and always 
wanted things her way, or only saw things her way.  Our mom told 
me that she didn’t understand how other people felt and that’s 
why she acts like that.  She never cared whether or not she was 
going to get in trouble.  She didn’t even think about it.  She 
always just does what she wants at that second.  A couple of 
years ago she got caught stealing stuff from a couple of kids, 
but she didn’t care.  She just “wanted” what they had.  She has 
no idea when someone wants her to leave or when she hurts 
someone’s feelings.  It’s like she just doesn’t get it.  She has 
no friends and still gets into fights with adults.  She lies a 
lot, but a lot of times she is like bragging so I know she is 
lying.”

Case History #2

       “DT is a 44 year old male who obtained a MA in English and 
Communication and before the lesion taught students full time at 
a community college.  Two years prior to illness he and his wife 
agreed to a divorce so he moved into a villa. Until his illness 
he was in good health.  He told me that after his operation, 
everything seemed fine for a while, and then he began to notice 
changes in his personality.  He told me that he couldn’t 
concentrate and had depressive thoughts.  He didn’t feel like he 
had any initiative to accomplish anything, and felt generally 
apathetic. He returned to his job part-time. He would “forget” 
to prepare his lectures for class and began to “lose control” of 
the teaching process and consequently lost his students 
attention.  He failed to perform his share of duties at the 
villa and was asked to leave, so he moved into a one bedroom 
apartment.  He soon after had to leave his job because he was 
unable to teach and was given disability for a while but due to 
budget cuts he was forced to come to me in help finding work.  I 
was able to find him a job at an office but he was chronically 
late and would “let down” appointments.  He says he is aware of 
missing appointments and being late and is ashamed of it, but he 
“just doesn’t do it”.  An increasingly sarcastic sense of humor 
that was frequently ill-timed made him unpopular around the 
office.  He also has a habit of making other “inappropriate” 
comments, but cannot seem to regulate himself from saying them.  
His personal hygiene was and is below standards which he is 
aware of but does not improve (he “just doesn’t”).  He was soon 
asked to leave that position.  He has no plans of any kind for 
the future, and doesn’t seem to think out any decisions.  He 
tells me he spends his time in his apartment, not doing much of 
anything except watching TV.”
       
       
       
References


Anderson, Stephen W., Antoine B., Damasio H., Tranel D., Damasio 
Antonio R. (1999). Impairment of social and moral behavior 
related to early damage in human prefrontal cortex. Nature 
Neuroscience,2(11),1032-1036.
	
Eslinger, Paul J., Flaherty-Craig, Claire V., Benton, Arthur 
L. (2004). Developmental outcomes after early 	prefrontal 
cortex damage. Brain and Cognition, 55, 84-	103.

Kalat, James W. (2004) Biological Psychology. Ontario, Canada: 
Wadsworth.

Lawson, C. “Social Skills and School” 
www.cdl.org/resources/reading_room/social_skills.html. May 3, 
2005.

Mah, Linda, Arnold, Miriam C., Grafman, Jordan. Impairment of 
social perception associated with lesions of the 	prefrontal 
cortex. American Journal of Psychiatry, 161, 	1247-1255.

Thimble, Michael.H. (1990). Psychopathology of frontal lobe 
syndromes. Seminars in Neurology, 10(3).

Trauner, Doris A., Nass R., Ballantyne A.(2001) Behavioural 
profiles of children and adolescents after pre- or perinatal 
unilateral brain damage. Brain, Vol. 124(5), 995-1002.


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