Wang 1

Eric Wang
Greene
AP Capstone7th
18 November 2016
Cognitive and Behavior Effects as a result of Traumatic Brain Injury
I. Introduction
The brain is the control center of the body and is arguably the most important human
organ. The brain controls motor functions, decision making, and keeps certain bodily functions at
equilibrium. Traumatic brain injuries, often induced by rapid acceleration or deceleration of the
head can damage the brain and negatively affect these bodily functions.
Steve James documentary, Head Games, and Michael Kirks, League of Denial, provides
fresh insight on the problems facing many professional athletes. These athletes put themselves at
risk for severe traumatic brain injury and are constantly exposed to rapid acceleration and
deceleration. These two documentaries along with an intrinsic interest in psychology were the
basis for my journey into the world of neuropsychology.
My interest in this topic was further accelerated by an independent research opportunity
provided by Capstone through the Global Studies Academy. With this opportunity, I focused my
research on how traumatic brain injuries affect a persons personality, behavior, and ability to
perform certain cognitive functions. My research was assisted by a psychology professor at the
University of Houston who provided me with helpful sources and insight on the topic, and my
research experienced was enhanced by constantly attending service learning at Sugar Land
Methodist Hospital. There, I was able to receive firsthand insight about traumatic brain injuries

Wang 2
as I volunteered in the neurology sector. I learned that traumatic brain injuries have long lasting
effects on victims as it prevents many from pursuing a career in their desired fields, whether by
hindering their ability to learn, or the constant need of medical attention.
II. Traumatic Brain Injuries (TBI)
Traumatic Brain Injuries can occur through external blunt force damage or rapid
acceleration or deceleration of the head without direct trauma to the head. These injuries not only
disrupt neuronal activity but changes oxidative metabolism and blood flow to the brain.
White Matter
Named for its pinkish white appearance, white matter serves as the communication
network between various gray matter centers in the brain. Since the white matter areas are
densely myelinated, it allows white matter to quickly relay messages from one section of the
nervous system to another in three ways: it can extend from the cerebrum to the rest of the body
through projection tracts, it can send messages across each brain hemispheres through
commissural tracts, and it can connect various regions in the same hemisphere through
association tracts1. While the white matter areas do not contribute to actual cognition, it affects
information processing and coordination. This means that damage to the white matter structure
can potentially have negative effects on areas associated with information processes such as
learning and memory.
Correlation between TBI and White Matter
It can be said that traumatic brain injuries can cause a change in the structure of white
matter, how it develops, and how it transports messages within the brain.

Wang 3
In recent studies, it was proven that there are correlations between individuals who suffer
from traumatic brain injury and disruption in white matter structure. According to a study
conducted by Doctor Kirsi Kinnunen, comparison of patients with traumatic brain injury and
age-matched controls revealed that the majority of the white matter showed some evidence of
disruption in the traumatic brain injury group.6 This means that people who suffer from
Traumatic Brain Injuries, whether from blunt force trauma or other means, have higher chances
of suffering from white matter disruption. From this, we can conclude that individuals who suffer
from traumatic brain injuries have a decreased ability to process and retain information. In a
further study conducted by Doctor M. F. Kraus, they observed cognitive changes that follow
[traumatic brain injuries] can include decreased mental flexibility, trouble shifting sets, impaired
attention, poor planning, lack of organization, problems with sequencing, impaired judgment,
deficits in verbal fluency, problems with working memory, as well as increased impulsivity.7
This confirms the idea that individuals who suffer from traumatic brain injuries have a tendency
to exhibit a decreased level of learning.
III. Effects of TBI
The effects of traumatic brain injuries can range anywhere from mild to severe. With mild
traumatic brain injuries, the victim often suffers from whiplash, neck pains, and blurry vision
whereas in severe traumatic brain injuries, on the other hand, victims suffer from much more
severe symptoms. These often include cognitive deficits such as a decreased ability to
concentrate, learn, and understand speech.

Wang 4
Executive Function
Executive functions, also called cognitive control and supervisory attentional system, are
processes such as memory, reasoning, problem solving, planning, and attention control. These
functions are vital as they practically control behavior and decision making. Executive functions
develop as people grow and experience new things and learn from the new things, but just as
they can develop with experience, they can also be adversely affected by external injuries or
other events.
As previously mentioned, TBIs can change the white matter structure of our brains. The
shift in white matter structure is the primary cause of the cognitive deficits that result from TBIs.
The change in executive function can be explained by the brain overlapping connectivity. Doctor
K.M Kinnunen states that it is likely to be because damage to brain connectivity is a critical
factor in the development of cognitive impairment after traumatic brain injury. Functions
commonly impaired, such as memory and executive functions, depend on the coherent activity of
widely distributed brain networks.6 What Kinnunen means by this is that executive functions
such as attention control, working memory, and cognitive reasoning require strong connections
between the different areas of the nervous system. As we know, white matter is the primary
pathway for nerve impulses, and with damage to white matter, it can almost be expected that
there would be a change in neurotransmission, and in turn behavior. This also means damage to
white matter changes brain connectivity, potentially affecting cognitive function.
Personality
Personality is often described as the characteristics and qualities that form an individuals
character.

Wang 5
Since white matter determines a persons personality, it can be safe to say that damage to
white matter will likely result in severe personality changes. Those who suffer from a severe
head injury, where damage to the connectivity of the brain was present, show signs of variations
in personality. In a study published by the Journal of Neurology, Neurosurgery & Psychiatry,
caretakers of patients who suffered from recent blunt force injuries to the head were asked to
document the patients behavior over a span of 12 months. According to McKinlay, the scientist
behind the study, in those patients whom the relatives described as having shown personality
change, the changes were in a negative direction, with reduced self-reliance, reduced sensitivity,
and increased irritability being strikingly evident even at 3 months after injury2, proving that
personality and behavior can, in fact, be changed with external damage to the brain. A more
severe example of personality change is Phineas Gage. In the infamous story of Phineas Gage, a
railroad construction worker, suffered from an accident where a large iron rod was driven
through his head, damaging the majority of his frontal lobe. The fact that he survived was
incredible, but what was more incredible was how his personality changed over time as reported
by his caretaker. In a study conducted on his miraculous case, professor Damasio stated, that it
had damaged the left prefrontal cortex, and that such damage probably explained Gages
behavioral defects, which he aptly described as a mental degradation.4 In a separate journal
published on Phineas Gage, there was a transcript of what Dr. John Harlow, the doctor taking
care of Phineas Gage, witnessed days following the accident. While doing so, he documented all
of Gages behaviors throughout his stay. Included in Harlows research was a chart detailing the
condition of Gage, from the changes in behavior to his delusions.9 The story of Phineas Gage
goes to show that damage to the brain through physical trauma can cause personality change.

Wang 6
IV. Treatment
Traumatic brain injuries often result in noticeable changes in behavior and cognitive
function; while there is a high likelihood that the victim will never be the same, there are
treatments such as hypothermic treatment and CB2 inverse agonists which could lessen some of
the effects
CB2 Inverse Agonist
CB2 Inverse Agonists, in short, are drugs that activate the cannabinoid type-2 (CB2)
receptor. A common CB2 Inverse Agonist, and the one being focused on is a drug called SMM189, which binds to the CB2 receptors and activates certain healing proteins.
When taken, the drug shows a significant decrease in neuron loss after traumatic brain
injuries. Traumatic Brain Injuries results in widespread axonal injury, loss of neurons, and a
variety of functional deficits; furthermore, the functional deficits are reduced by targeting brain
cells through the CB2 receptors using a daily administration of the CB2 inverse agonist known
as SMM-189. According to Doctor Wei Bu, [SMM-189] stabilize the G-protein coupled CB2
receptor in an inactive conformation, leading to increased phosphorylation and nuclear
translocation of the cAMP response element binding protein (CREB), and thus bias activated
microglia from a pro-inflammatory M1 to a pro-healing M2 state.3 Simply put, SMM-189
activates the binding protein, CREB, which activates brain cells from an inflammatory state into
a healing state, aiding in brain development and offsetting many of the minor cognitive effects of
traumatic brain injuries. In a separate experiment conducted by Doctor L Sterin-Borda to test
how the inverse agonist, SMM-189, affected neuron loss, SMM-189 was shown to yield 50
60% rescue of Thy1+ and parvalbuminergic-neuron loss in the basolateral amygdala.11

Wang 7
According to both of these studies, it seems by using the CB2 inverse agonist, SMM-189,
scientists are able to prevent or slow down nerve damage resulting from traumatic brain injuries.
Hypothermia Treatment
Scientists have also found that treating traumatic brain injuries with moderate
hypothermia significantly decreased certain effects of traumatic brain injuries. One possible
explanation on why this works, according to Doctor D.W. Marion, is because, traumatic brain
injury initiates several metabolic processes that can exacerbate the injury. There is evidence that
hypothermia may limit some of these deleterious metabolic responses.8 This means that with
damage to certain areas of the brain, several metabolic processes which can worsen the injury are
triggered. By using hypothermic treatments as opposed to normothermic treatments, it could
slow down the metabolic processes and reduce the effects of any brain injuries. In an experiment
conducted by Doctor D.W. Marion, it was shown that the hypothermia group had a lower mean
intracranial pressure, cerebral blood flow, and heart rate and a higher mean cerebral perfusion
pressure.8 By suppressing the brains post traumatic inflammatory response, hypothermia
treatment reduces secondary brain injury and prevents the patient from suffering further brain
damage.
Cytokines are substances that are secreted by the immune system and have effects on
other cells. In this case, the cytokine, interleukin-1 has effects on brain and nerve cells.
According to Doctor Louis E. Penrod Interleukin-1 is one of several cytokines that appear in
the ventricular cerebrospinal fluid soon after traumatic brain injury in humans. Since
[Interleukin-1] promotes the adhesion of leukocytes to endothelium and increases capillary
endothelial permeability, interleukin-1 is undoubtedly important in initiating the post-traumatic

Wang 8
inflammatory response.8 In the same experiment conducted by Doctor D.W. Marion, it was
found that concentrations of interleukin-1 are significantly lower in patients who undergo
hypothermic treatment than in patients who were not administered hypothermic treatment,
essentially proving the effectiveness of hypothermic treatments.
Exercise
Things as simple as exercising are also seen as an important step to cognitive recovery
after facing functional deficits from traumatic brain injuries. Many scientists argue that
pharmacological agents do not help patients with their functional deficits in the long run.
According to the Journal of Neurosurgical Anesthesiology, the evidence for stimulant
medication having a significant or long-lasting impact is limited and this approach also exposes
the patient to adverse or potentially serious side effects.5 They believe in treatments such as
exercise in order to increase neurotransmitters and neuroendocrine activity in the brain, because
according to scientists such as Doctor M.A. Grealy, alterations in neurotransmitter and
neuroendocrine activity in the injured brain have been linked to behavioral changes and underlie
abnormalities in arousal, mood, and cognition.5 From this, we can conclude that exercise could
be an effective method to treat behavioral changes in patients suffering from traumatic brain
injuries.
Personality Treatments
The effects of traumatic brain injuries on personality are incredibly hard to treat. For one,
scientists can treat certain effects only if they know where it originates from, and which parts of
the brain they affect. Personality, on the other hand, is an incredibly complex trait and scientists
have argued for decades on how personality is shaped and formed. What we do know is that

Wang 9
personality is the characteristics and qualities that form an individuals character. Scientists have
come up with various theories to try and understand how personality is shaped such as the nature
theory and the nurture theory. While these theories do point in the direction of uncovering more
about personality, in order to make further advances in neuropsychological studies, scientists
need to take into consideration that personality is too complex of a trait to pinpoint to one
specific area.
When scientists first started to examine personality and behavior, they took a nature
approach to it, studying the biology and genetics that contribute to how an individual behaves.
According to Lars Penke, in the early years of examining personality, scientists studied the link
between genetics and personality through a series of experiments involving twins and siblings.
While blood siblings share roughly 50% of genetics, identical twins share nearly 100%.
According to these studies, there was a much higher correlation between the personalities of the
twins than the siblings. The scientists then concluded that when it comes to personality, genetics
has a huge impact10. The question then arises, is there a personality gene? This is where it gets
difficult. After years of studies, scientists concluded that personality was too complex of a trait
for genetics to be the only factor. In fact, according to Penke, in the subsequent [genetic]
research, many researchers were left disappointed. Specifically, for every breakthrough finding
linking a specific SNP (single nucleotide polymorphisms) to a personality characteristic, there
was a null replication. Several of the most promising candidate genes, such as the MAOA gene
which has been linked to antisocial behavior in past research (Caspi et al., 2002), have failed to
replicate in subsequent work, according to several meta-analyses (De Moor et al., 2010)10.
Many scientists who take a nurture approach to personality use this as evidence that an
individuals personality is shaped by the environment the individual is raised in, but with the

Wang 10
twin studies, this only proves that personality is simply too complex of a trait to be one or the
other, and is instead, a combination of both environment and genetics.
Research suggests that the influences genetics have on personality are ubiquitous,
however, the effects that childhood development and environment have on an individual often go
unlooked. As scientists were studying personality for the first time, they viewed it as any other
character trait, claiming that many of Darwins evolution theory can be applied to personality.
According to Darwin, traits that help increase survival are likely to be passed down generations.
If this were the case, why is there such a genetic variance on personality traits? Well, according
to psychology professor Lars Penke, it is not enough for a trait to be neutral in some
environments or during some periods, because selection is very efficient at favoring
polymorphism with higher average fitness outcomes across all relevant environments. Only a
fully balanced effect of different alleles across space and time will work to maintain genetic
variations.10 What Penke means by this is natural selection does not apply to personality if there
is no environmental heterogeneity. In short, environment plays a huge role in shaping an
individuals personality. Furthermore, according to the American Psychological Association,
childhood trauma, and the influence of peers greatly affect a childs personality. This can be
explained by the fact that the frontal lobe of the brain, the part that controls emotions and
personality, continues to develop as a child ages so that external influences changes how the
frontal lobe forms. With this in mind, it seems obvious that personality is influenced by the
environment; however, the years and years of twin studies and genetic research seem to prove
otherwise, pointing only in the direction that some areas of personality area shaped by the
environment and human experiences, while others are due to genetics.

Wang 11
As of now, the only way to treat personality disorders or personality onsets as a result of
TBIs, is with drugs that only suppress the change of personality, but does not treat it completely.
By altering neurotransmitters, medical professionals are able to change a patients mood and
behavior, but only for a limited amount of time. The extent of personality treatment are short
term neurotransmitter drugs, and rehabilitation, are not the most effective form of treatment.
V. Conclusion
White matter serves as the primary communication network between various centers of
the nervous system. We can conclude that since both cognitive and behavior function stem from
the connectivity of the various regions of the brain, and white matter serves as the neural
pathway of our body, change in white matter structure could result in changes in behavioral and
cognitive functions.
There are several factors that play into how or what causes the various effects of
traumatic brain injuries. While there is currently no way to permanently reverse the damages
from these injuries, there are several ways to suppress many of the negative effects these injuries
bring. From the experiments mentioned, we can conclude that exercise, hypothermic treatment,
and CB2 Inverse agonists all play a role in suppressing certain aspects of traumatic brain injuries
and serve as viable rehabilitation methods.
However, treatments that treat personality disorders have not made much progress in the
past few decades. There are drugs that suppress personality disorders, but none that completely
cures them. This can partly be attributed to the fact that scientists cannot seem to agree on what
personality is and how personality develops. In order to make advances in personality treatments,
scientists need to first establish what personality is.

Wang 12
Works Cited
&na; &na; Definition of mild traumatic brain injury. Journal of Head Trauma Rehabilitation.
1993;8(3):86-87. doi:10.1097/00001199-199309000-00010.
Brooks DN, Mckinlay W. Personality and behavioural change after severe blunt head injury--a
relative's view. Journal of Neurology, Neurosurgery & Psychiatry. 1983;46(4):336-344.
doi:10.1136/jnnp.46.4.336.
Bu W, Ren H, Deng Y, et al. Mild Traumatic Brain Injury Produces Neuron Loss That Can Be
Rescued by Modulating Microglial Activation Using a CB2 Receptor Inverse Agonist.
Frontiers in Neuroscience. 2016;10. doi:10.3389/fnins.2016.00449.
Damasio H, Grabowski T, Frank R, Galaburda A, Damasio A. The return of Phineas Gage: clues
about the brain from the skull of a famous patient. Science. 1994;264(5162):1102-1105.
doi:10.1126/science.8178168.
Grealy MA, Johnson DA, Rushton SK. Improving cognitive function after brain injury: The use
of exercise and virtual reality. Archives of Physical Medicine and Rehabilitation.
1999;80(6):661-667. doi:10.1016/s0003-9993(99)90169-7.
Kinnunen KM, Greenwood R, Powell JH, et al. White matter damage and cognitive impairment
after traumatic brain injury. Brain. 2010;134(2):449-463. doi:10.1093/brain/awq347.

Wang 13
Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM. White matter
integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging
study. Brain. 2007;130(10):2508-2519. doi:10.1093/brain/awm216.
Marion DW. Treatment of Traumatic Brain Injury With Moderate Hypothermia. Journal of
Neurosurgical Anesthesiology. 1998;10(1):55-56. doi:10.1097/00008506-19980100000013.
Neylan TC. Frontal Lobe Function. JNP The Journal of Neuropsychiatry and Clinical
Neurosciences. 1999;11(2):280-281. doi:10.1176/jnp.11.2.280.
Penke L, Denissen JJA, Miller GF. Erratum: The evolutionary genetics of personality. Eur J Pers
European Journal of Personality. 2007;21(5):i-i. doi:10.1002/per.656.
Sterin-Borda L, Zar CFD, Borda E. Differential CB1 and CB2 cannabinoid receptor-inotropic
response of rat isolated atria: Endogenous signal transduction pathways. Biochemical
Pharmacology. 2005;69(12):1705-1713. doi:10.1016/j.bcp.2005.03.027.