Bb1 15 past lecture summaries

Brain and Behavior Lecture #1 - Introduction Page 1 of 4
Announcements:
This is Brain and Behavior. Thanks for showing up.
I hope you guys will come to the lecture. I’d like to keep the other lecturers happy. There is also the benefit to you as future clinicians.
But I do understand that you won’t find all the lecturers equally important.
For the most part, if you have questions, it is easiest to email the individual lecturers. They are very willing to answer emails. You can
also send the emails to me and I can forward them on to the individual lecturers.
Lecture:
WHAT IS THE VALUE OF A COURSE ON CLINICAL NEUROSCIENCE FOR A MEDICAL STUDENT?
ANSWER
Brain disorders are the leading causes of disease and disability, and it is a growing population of chronic patients (e.g. traumatic brain
injury a.k.a. TBI, stroke, and dementia). You will find that there is a correlation between brain diseases and chronic diseases. If you
are not aware of it, you might miss serious consequences for the patients.
So the conclusion is that learning about the brain is good!
GOALS OF BB COURSE
We want to integrate and extend certain information presented in neuroanatomy, as well as develop an understanding of the reciprocal
relationship between body and brain in disease. Also, we want to learn about basic tools of “lab” evaluation in clinical neuroscience
(e.g. neuropsychiatry), such as functional imaging and neuropsychological testing. We also want to learn about basic neurobehavioral
functions e.g. memory, language, executive functions, and aspects of neurochemical and neuoanatomical substrates. So this course
will provide examples of certain disorders that will integrate previous lectures as much as possible.
For example, when we think of schizophrenia -- it is both a psychiatric and neurologic disease.
UNTITLED SLIDE
The final exam focuses primarily on material presented in lectures. I only ask the other lecturers to give one reading each. Some of the
references may be useful to you for future. For example, today’s handout is useful for clinical neuropsychiatric testing.
Please give feedback. If you give feedback, you are encouraged to be constructive and to give specifics and examples. And be
professional. This will help me to understand how to further develop the course. I will keep copies of all comments sent to me for
review purposes. I would appreciate comments e-mailed after lectures or at intervals whenever you can.
READINGS FOR THIS LECTURE
I put the Neuropsychiatric Exam Chapter on Blackboard. It’s a bit lengthy, but a good resource.
In addition, a very good clinical resource book is: The Mental Status Exam in Neurology by Richard Strub and F. William Black --
very practical and portable. I don’t know which edition is the most recent. Good to have, but not required reading.
NEUROBEHAVIORAL FUNCTIONS
This just refers to the entire spectrum of cognitive, mood, and behavioral functions – for example, integrating sensory-motor function.
In terms of neurobehavioral function, the brain is specialized in some ways, but much overlap exists. For example, the frontal cortex
circuitry we will talk about in a later lecture
EXAMPLES OF MECHANISMS OF BRAIN DYSFUNCTION
Brain dysfunction can be due to structural changes including:
Focal lesion-- focal damage or disease such as stroke, bleed, contusion. White or gray matter can be involved.
Diffuse axonal injury ( DAI )-- can be wider spread structural damage to white matter, such as due to trauma.
In addition, you can have:
Electrical abnormalities — seizures and epilepsy. Abnormalities are a spectrum.
Chemical/metabolic abnormalities – disturbances in neurotransmitter systems or metabolism. Such as due to substance use,
medications, systemic illness. This can range from schizophrenia to stroke and brain injury.

The thing to keep in mind is some illness or injury can be due to or result in a combination of the above. Such as TBI, stroke, delirium,
seizures presenting as mental status changes, drug induced dysfunction. For example, degenerative disorders, like Alzheimer’s
disease, can involve several mechanisms. So with many illnesses, several of these processes can be in play. Even in Parkinson’s
disease, a number of things can contribute to the ultimate clinical features of neurobehavioral function.
OVERVIEW: NEUROANATOMY AND FUNCTION
We know that neurobehavioral function is dependent upon specific brain areas, but also networks of areas, and their connections
(white matter tracts). So while we associate the frontal cortex with a certain function, we understand that other parts of the brain serve
as part of the network for those functions. So what that means is you can get dysfunction from direct damage to the frontal lobe or
dysfunction from cortical or subcortical damage. For example, in Parkinson’s disease, the frontal lobe may look fine, if it can’t
connect to the cortical and subcortical areas, you can see frontal lobe dysfunctions.
So functional deficits can result from dysfunction of a specific area of brain (mechanisms we discussed), as well as other parts of a
network, or to the white matter tracts that connect areas of a network.
RELATIONSHIP OF NEUROPATHOLOGY TO CLINICAL EFFECT
The effect of any neurological damage or dysfunction is going to be determined by several factors:
Obviously, size -- in general, greater area means worse deficits. Also keep in mind that location is key -- specific brain region, part of
network or WM tracts involved.
But remember that a strategically located smaller lesion/disease process could cause as many or more problems than a larger area of
damage in another location -- so where is the damage? For example, a range of thalamic lesions can do a lot of damage.
CORTEX
Bottom line is that there is not area of the brain that doesn’t contribute to neurobehavioral function.
CORTEX-OVERVIEW
Cerebral Cortex – damage/dysfunction of different areas of cortex can result in a variety of neurobehavioral deficits: motor sensory,
language, etc. For example, temporal lobe dysfunction can result in memory disorders, language problems, personality and behavior
changes associated with temporal-limbic areas (e.g. types of epilepsy, trauma).
Frontal cortex dysfunction can result in higher level cognitive problems, mood and behavioral disturbances, and language problems.
This is one of the areas that can be a bit of an imposter sometimes. They can present with frontal cortex symptoms, but can really be
due to damage elsewhere.
CORTICAL-SUBCORTICAL CONNECTIONS
Remember that “unplugging” cortex from subcortex can also produce cortical deficits when involving key parts of the network, or the
white matter (the “cables” linking networks). So it’s not that simple in thinking that someone with frontal lobe symptoms has damage
to the frontal lobe. For example, infarct of the inferior genu of the internal capsule, a strategic location, can interrupt the thalamic
peduncles and cause dysfunction of ipsilateral frontal cortex. Confusion, memory loss, apathy and memory loss can result.
Example: Parkinson disease can cause executive dysfunction (frontal cortex) due to disruption of cortical-subcortical connections.
THALAMUS
Anyone who wants to know about the thalamus can ask Dr. Gorelick about the thalamus. That’s his favorite part of the brain.
THALAMUS
The thalamus has multiple functions. It constitutes the main part of the diencephalon. It processes and relays sensory information
(except olfactory) selectively to various parts of the cerebral cortex. Its major role is on motor systems.
Thalamic nuclei have strong reciprocal connections with the cerebral cortex.
Neurobehavioral function: For example, damage to anterior and dorsomedial thalamus can result in wide range of neurobehavioral
dysfunction such as arousal, attention, motivation, executive function, memory deficits e.g. thalamic stroke syndromes. We’re
interested in the dorsal medial thalamus.
BASAL GANGLIA
You don’t have to memorize the chart. The basal ganglia are also a critical part of the network. Strokes and degenerative processes in
that area are not good.
UNTITLED
Basal ganglia are part of many networks. They play a role in movement disorders, psychiatric syndromes and cognitive deficits
(including aspects of learning) e.g. Parkinson Disease, Huntington Disease, Lewy Body Disease, and vascular disease. E.g. caudate
infarcts can result in cognitive and behavioral deficits. There can be impaired problem solving ability, memory problems, attentional
problems, and “frontal” type deficits (remember networks, tracts).

LIMBIC SYSTEM
UNTITLED
The limbic system is a complex network of areas and circuits that includes the hippocampus, cingulate , amygdala, and hypothalamus
as major components. Its role is in arousal, mood, attention, learning, memory, and regulating goal driven behaviors (more in a later
lecture by Dr Herbner). There are major white matter pathways- such as fornix, medial forebrain bundle- that have connections to
prefrontal cortex (PFC). Disruption of either the area or the connections can cause deficits/changes. For example, seizure disorders in
the limbic areas can result in primarily neurobehavioral presentations (Dr. Schrift lecture will cover neuropsychiatry seizures).
So again it is another example of the brain that also has discrete function; it has major connections and damages can result in wide
variety of symptoms. Presentation could be a primary psychiatric disorder, but you don’t want to miss something else medial.
CEREBELLUM
This area is involved in motor coordination and eye movements, but also a role in motor learning, attentional activation and other
aspects of cognition. Be aware of cognitive, affective, and behavioral disturbances in assessing, treating, and rehabilitating patients
with cerebellar illness. Further, it may be important to consider the possibility of cerebellar disease in patients presenting with a new
onset of changes in these behavioral domains. Things to keep in mind when patients present: Think of the possibilities of lesion and
disease processes.
NEUROBEHAVIORAL FUNCTION AND DIAGNOSIS
So all this is to stress that changes in mental function may present symptoms for psychiatric, neurological, or medical disease. Never
just assume a primary psychiatric disorder – e.g. in cognitive, mood, behavioral changes, or psychotic features in delirium, vascular
disease, and stroke. They may be mistaken for a primary psychosis. Particularly in the elderly and very young, delirium can result in
other missed things. You can have very low level delirium. So that’s an instance where you need to have very high level of suspicion.
Inappropriate behavior, poor attention, language problems can present in traumatic brain injury or types of dementia. Vascular disease
may first present as changes in cognition, mood, behavior, with certain tumors or endocrine disorders. Depression or cognitive
changes in cerebral vascular disease, Parkinson’s or Alzheimer’s disease
NEUROPSYCHIATRIC EVALUATION -- GENERAL GUIDELINES
History and exam are key points. Part of the neurologic exam looks at higher cortical functions. You can’t stop at sensory motor
exams. The laboratory tests are obviously driven by the history and exam. Neuropsychological testing will be another lecture. EEG
should be done as necessary, but normal EEG does not always rule out underlying seizure disorder. The same goes for imaging - CT,
MRI (lecture on MRI to come). But you have to be careful because these things are costly. But sometimes you can miss things. So on
EEG, if you see something, great. If you don’t, don’t rule it out. So it’s good not to be too reliant on lab tests and take it as part of the
big picture. Often the clinical exam and history are still primary basis for diagnosis.
MMSE
Example of the Folstein MMSE- Make copies and use this!
It is a good, brief, standardized way of assessing mental state. This is quite sensitive for someone developing delirium. If they get
28/30 on this, it’s likely they know what’s going on. This is a nice standardized way to check patients’ mental status.
CLINICAL NEUROSCIENCE AND NEUROPSYCHIATRY: CASE EXAMPLES TO ILLUSTRATE SOME COMMON
CLINICAL SITUATIONS
Now what I want to do with the time left is talk about why all this matters.
CASE EXAMPLE
You need to ask whether there have been additional changes. If someone is not challenged on a daily basis, it’s difficult for people to
remember exactly when something started. Is there anything that concerns you in this history? Alcoholism. What else? So we get more
history on the next slide.
NEXT SLIDE
So he fell, and now he is poorly orientated and distractible.
So maybe he has a chronic subdural hematoma! Acute subdural hematoma is not hard to diagnose. But chronic ones are difficult
because it’s a low pressure bleed. With alcoholics, they may not remember when they fell. So this can be missed when physicians
aren’t thinking about it. These can present as a mood disturbance.
EXAMPLE OF SUBDURAL HEMATOMA (IMAGING)
This is such a common tool. So you need to understand how to interpret it.

CASE EXAMPLE
So what other type of information would be useful?
NEXT SLIDE
Detailed questions reveal that the family notes personality changes- the patient seems progressively more irritable and impulsive. As
for cognitive changes according to the family – they note that he has been more distractible, more forgetful. Patient has history of
hypertension, hyperlipidemia, and insulin-dependent diabetes.
On exam, you note mild cogwheel rigidity (generally a Parkinson’s symptom), and MMSE is 22/30. What are you considering at this
point? What work-up would you request? So what jumps out at you? This might be a stroke!
Based on results of your exam and history, you may order further tests:
NPT (neuropsych testing) may be first, unless changes are acute.
NPT shows cognitive impairments, with impairments in memory, attention and executive function.
Imaging? This is not an acute problem, so you’re not going to get an emergency scan. But at some point, you might get a scan.
What differential diagnoses would you be considering now? What do you want to do?
NEXT SLIDE
The point here is to make the point that these patients may go to clinic for depression or suffering from a mood disturbance, but there
may be something else going on.
CASE EXAMPLE
Especially with young people, you have to ask about previous head injuries. This person actually has history of significant head injury.
So this type of mood disturbance can look sociopathic.
NEXT SLIDE (IMAGING)
This shows 3 types of MRI structure scans. The FLAIR and GRE show abnormalities in the left frontal lobe area.
CASE EXAMPLE
This is another elderly person with a common problem. You are an intern on the inpatient medicine service, and an 80-year-old
woman is admitted for respiratory problems and fever. She is diagnosed with pneumonia and placed on antibiotics. She seems calm
and cooperative. Her fever comes down, and her infection is responding, but she is tearful at times and seems withdrawn. The family
is concerned she is depressed. What kind of things do we need to worry about? This is another case of low level delirium.
NEXT SLIDE
You perform a detailed mental status exam (MSE), and find the patient is not oriented, is distractible, has poor short term memory,
and cannot copy the picture. She becomes tearful. After you speak with her for awhile longer, she expresses concern that one of the
staff is poisoning her food. She also asks you to do something about the bugs in her room. Family denies any past Psychiatric history.
What’s going on? With the elderly it is not uncommon for there to be lag time between injury and onset of symptoms.
DELIRIUM
Encephalopathy may signal a medical emergency. This may be presentation of a serious illness. It is critical to distinguish from a
diagnosis of depression or psychosis. It may be difficult to do this. The elderly are very prone to delirium, and the deficits often linger
after the medical problem is treated. Serial MMSE can show some resolution of the process. This disorder is excellent example of the
confluence of medicine and psychiatry. Sometimes with only a UTI, the elderly can develop delirium.
CASE EXAMPLE
The patient looks very manic. But what are the odds of developing bipolar after 40 years old? Not very likely.
NEXT SLIDE
You get a complete medical history. The family says she has no history of any psychiatric disorder. She has been relatively healthy in
the past, except for a history of asthma which can be severe at times. She was recently put on a round of corticosteroids. They also
worry she may have been taking more of her asthma medication, theophylline, than she should, as she forgets that she took them
sometimes.
SECONDARY MANIA
To conclude, you just have to keep in mind that neurobehavioral problems can present as psychological problems. If you misdiagnose
a medial/neurological problems as a psych problem, you will do more harm.

Brain and Behavior: MRI in Clinical and Research Neurosciences
Announcements: See Blackboard for schedule changes. Readings for this lecture are not required but are for those who want to
know more about the area.
Lecture Content
Today we are going to talk about MRI and the role it plays in the clinical neurosciences. Let me walk you through the
procedure and process of MRI. This is a big magnet that is on at all times. When you go toward the scanner you will see that there are
markings on the floor so people with pacemakers, metal, etc. shouldn’t go in. The precautions are important because the bigger the
magnet the bigger the risk. So if you’re going in the scanner what happens is you are being put in this large, static, magnetic field
that’s always on.
What we are particularly interested in, in biological systems, is the hydrogen atom because there are a lot of them in biologic
systems. They act like little magnets and have random movement and we can do a lot to them in MRI which allows us to pick up
signal and look at different tissues. Different tissues are going to have different concentrations and locations of hydrogen atoms. They
are positively charged and have a nuclear spin. They normally spin in random directions.
(Slide 5) The idea is that they are random so that you have a net magnetization of zero. The first thing you are trying to do in
an MRI scan is get your hydrogen atoms in a more consistent state. If you want to get a measurement out of them you have to get them
in order first. The hydrogen atoms in a static magnetic field are going to try to line up either parallel or anti-parallel to the field. It is
easier to measure change from a more uniform state so you are setting the stage for the measurements you are going to get.
T1 is the value of time it takes for the hydrogen atoms to line up with the static field. The T1 constant is different for different
tissues and we take advantage of this. When you are put in a scanner a cylindrical coil is placed around your head, the type of coil you
use corresponds with what you look at and the sensitivity of it. The coil can transmit and receive signal. We transmit a radio frequency
pulse to your brain that is strong enough to overcome the static field. This frequency is going to try to make those hydrogen atoms
move again. They will shift and line perpendicular to the static magnetic field. So thus far you have manipulated the protons twice.
Then when you turn the RF off the protons want to go back to where they were in the static field.
The time it takes them to decay (go back to align with the static field) is the constant T2 and it is also going to be different for
different tissues. This is what we want to take advantage of and there are so many different sequences we can use depending on what
we want to look at. Things such as water and lipid content will affect the signal. We scan an area and get a reconstructed picture that
looks a lot like the real thing. In reality it is done many times, we collect the data and it is processed to develop and image.
Slide 10 is a fundamental example of T1. Basically the difference is T1 CFS looks black T2 CFS looks white. That’s just a
generality because it can vary to some degree. This website whole brain atlas is a great resource to use.
Slide 11 is an example of T2, take note of the difference.
Slide 13 is a picture I showed in the first talk. It was a patient we thought to have vascular dementia. Is this T1 or T2? T2.
Again to jog your memory from the first lecture, what structure is this pointing to in slide 13? Hypothalamus.
It is important as a clinician to know something about the technology of MRI to know how serious to take the reports you get
and how to interpret them. A lot is dependent on the scanner that’s used, the skill of the people that set it up, sequences that were used,
size of the magnet, and whoever is doing the post processing. There are more steps that can make it a better tool but also leave a little
more room for mistakes. For the size of the magnet in general, bigger is better but there are limitations because the larger the magnet
the more concerns to worry about. It is usually measured in Tesla units. A lot of clinical scans are 1.5T. We have a 3T as well and it
gives you better sensitivity and resolution.
So how do we use the MRI? First and foremost we can assess structure. We can look at blood plot and get an idea about
perfusion and that is routinely done clinically. It is also used to assess function, a lot of us are doing research on this but it is not yet
used routinely for clinical purposes. It is used in some procedures to help guide neurosurgeons in terms of understand where viable
and nonviable tissue is etc.
CT is similar to an x-ray and is very useful acutely. People that come into the ER with traumatic brain injury first get a CT
scan. It gives you what you need for acute triage but will not give you better sensitivity to look in more detail at more subtle aspects of
injury. MRI has a lot of flexibility, CT does not have setting you can play with to look at more specifics. MRI has a number of
parameters you can adjust to look at different things.
Once you start looking at MRI reports, these are terms you may see. A good report is going to tell you what sequences were
done. A bad report is just going to tell you this MRI is normal. If you need to look at something specific you need to ask what you
should order because they may just do a general scan that won’t be helpful to you. Flair is often used to look at white matter because is
helps eliminate the high signal intensity of CSF which messes up your ability to look at other structures. Gradient-recalled echo (GRE)
is very sensitive to blood product. If anyone has ever had a contusion in the past, blood product never completely goes away so GRE
is more sensitive to identify even a bleed from years ago. Be aware if the different sequences for different things, not all MRIs are the
same and you need to know that clinically and if you go into research.
Slide 18 hopefully looks familiar, this is the example I showed you in the intro lecture of a traumatic brain injury patient that
I actually saw a number of years ago. This gentleman had a pretty significant injury and was comatose for a period of time. We looked
at these three images and as you can tell some of them make the lesion look more identifiable. This gentleman has encephalo
(inaudible) in the left frontal lobes, it is just a fancy term for dead tissue, mush, it’s gone. You can see the tissue loss in the left frontal
area. It’s quite obvious on the flair you also can see some changes her in the white and gray matter. In the GRE you can see it. If you

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look at anther type of sequence though, an SPGR, it’s not as easy to see the injury. These are the same level, same patient, same
scanning session.
Let me talk about diffusion tensor imaging (DTI). The grandfather of DTI is diffusion weighted imaging. That has been
around for a little while and has been useful in disorders like stroke. It takes advantage of the fact that water molecules do not diffuse
the same in all directions of brain tissue. It’s going to depend on the tissue structure, how highly structured it is, what gets in the way
of the water. If the molecules are left to their own devices they have random motion and tend to diffuse randomly or spherically. If
there is no obstruction you will see random diffusion equally in all directions. In biologic tissue you know there is going to be
restriction to that movement so we take advantage of that to reconstruct the tissue particularly the microstructure of white matter
which we know is more structured than gray matter.
Isotropy and anisotropy are terms that refer to the diffusion. A good example of isotropic diffusion is dropping ink into a
bowl of water and it diffuses spherically because there is no restriction in any direction. The opposite is that you would have complete
restriction, anisotropic. So in reality you don’t get a 0 or 1 in biologic systems, you get somewhere in the middle. In healthy tracts you
have more limited directionality in healthy white matter than you do in gray matter, in other words there’s more random diffusion in
gray matter. Q: what do you mean by restriction? A: Restriction means the molecule meets barriers like tissue. Diffusion tensor
represents the 3-D image of diffusion in any area of the brain and it is usually elliptical.
One of the measures we use a lot is FA (fractional anisotropy). It gives you a number that tells you how restricted the
diffusion is in that tissue. 1 reflects completely restricted diffusion, 0 for diffusion like ink in water. So again in reality it’s going to
diffuse between 0 and 1. So white matter may be .4 and gray matter .1. There is slight variability so when we do research we use a
control group to compare FA values with. You can get an FA value for a voxel or for the whole brain, which will be more of an
average. It is really nice to use it to look at specific areas and specifics tracts of interest.
Another thing you can do that is sort of the “bling” here with DTI is tractography. If you take the FA values and you
take a seed voxel wherever it is you want to start to look at specific tracts and where they go in the brain, statistical software grows the
white matter tracts for you and you get a visual like this that actually looks very much like the real thing. We don’t really do group
data this way right now, it’s more of something that gives a pretty picture.
There’s a more practical application of DTI is when you are looking at FA maps and this is an example of that. So you have
an anatomical scan here, and here is an FA map. Basically what it is telling you is that the hotter areas are the denser white matter
areas. So as you would expect your corpus callosum is one of your densest white matter tracts. Some of the more slender white matter
tracts may not stand out as much. This is just a map generated by FA values and yet it closely resembles the anatomical scan. For
many more subtle white matter dysfunctions it is not going to be adequate to just inspect the map. You will need something more
quantifiable and that’s why we look at specific regions and do statistics on those and compare them to the health individual data.
So let me give you some examples. This is the paper you had in the additional reading and I want to go over it a little bit to
make sense of how we use it in context. What we did is looked at chronic traumatic brain injury subjects of all severity. We had 18
healthy controls. We obtained DTI levels and neuropsychological testing which will be talked about later. Slide 27 is an example of
region of interest maps. We did this by hand. This gives you an example of how we label the white matter tracts we are interested in.
We color code it so we know what we are looking at. We found the moderate/severe subjects had abnormalities in all 13 regions we
were interested in. They are pretty damaged. The mild traumatic brain injuries including those with concussions with or without
consciousness had abnormal white matter, it was only significant in 3 of the areas we were interested in but the take home message is
even without severe injury there all alterations in white matter. It has consequences and creates vulnerability even if you recover well.
What we did is decide to take those 13 regions of interest and get a number. So for every subject in the study including the healthy
controls we added up the number of areas in that met certain criteria of abnormality of FA (we picked a cut off point). So each person
had a defined number and we called it white matter load. It was a way of getting a global measurement of white matter disorder in that
individual. It was significantly different between the controls, the milds, and the severes.
I wanted to show slide 30 as an example of what we are able to do now with DTI. What we were able to do is not just look at
the white matter tract; we were able to look at the relative contribution of axonal damage vs. myelin damage. This is an incredibly
important tool in studying disorders like MS. The myelin integrity as well as the axonal integrity are going to make up the FA value,
we think we can actually look at them separately. What we found is the moderate/severes both seemed abnormal and with the mild the
myelin seemed relatively intact but there was irreversible axonal damage.
A little bit about Functional MRI. This is more of a research tool as well. The big difference is that structural MRI including
DTI looks at structure vs. fMRI which is an indirect way of looking at activity by looking at changes in blood flow which is affected
by metabolism. Different brain regions and different networks are going to be specialized to perform different functions. When an area
is activated when doing an activity obviously the area is going to have increased blood flow and metabolism. So we are using that to
then end up with the information we get for fMRI. fMRI will help you localize area that are more or less activated during particular
tasks. The basis of this is when neurons become more active obviously they are using more oxygen, there is increased metabolism and
this if followed very quickly by increased blood flow in the area. There is a net decrease in the amount of deoxygenated hemoglobin
present. It changes the magnetic quality.
The BOLD technique is the way we do all of our fMRI studies. This is a schematic to show you that when you are at rest this
is the amount of signal that is going. If you do a task like moving your finger there is an initial dip then a rise, it plateaus, then there’s

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a decay and a bit of an overshoot. This is the model we have and use. So again depending on how much oxygen is in the area at the
time it changes the magnetic quality of that blood and that is what allows us to look at certain areas.
Activation tasks for imaging can be anything you can do in a scanner safely. Obviously you want to choose a task depending
on the area you want to look at specifically. Simple motor tasks are done most often but you can also do more complicated cognitive
tasks depending on what questions you want to ask. You can have a button press and a screen the person can see. One of the tasks we
do is an oculomotor task. Eye movement task are simply having a person follow a target but it is a sensitive indicator of the integrity
of a lot of neural circuits that a lot of us are interested in research.
This is the fMRI testing environment. Essentially we have to set op a mirror, camera, projector, there’s a lot we have to do
and there are limits.
This is what we might see if we had them do a basic visual saccade task. They are simply following a target but they may
activate very differently depending on how their brain is working. The more intense regions are representing more activation.
To end, this is once again our traumatic brain injury patient. We acquired all these different sequences. We saw the structural
scans already. In the FA you can see there is some loss of symmetry and therefore loss of white matter. In the fMRI it may not be as
obvious to you but take my word for it there should be more activity on this side.

Brain and Behavior 3: Prefrontal Cortex Function and Dysfunction
Announcements:
Just a few quick announcement before I forget. Just a reminder to check the schedule. I just had to shift a couple of lectures around to
accommodate the time issue. And the last scheduled lecture, which was originally going to be Dr. Klarity (sp?), who traditionally
gives a lecture in this course, he will be unable to because he will be out of town. Since that’s the last lecture, it’s just going to be
cancelled. So the revised schedule is online now and it reflects that change. For those of you who were very interested in the physics
of MRI and had questions that I could not answer, I did download some notes, completely optional. For some people who had good
questions about T1 and T2, I don’t think I did a very good job explaining that detail. I did add an extra reading to the documents for
anyone who is interested and it’s optional. Also, I just wanted to mention that in the past, some students who were particularly
interested in psychiatry and in seeing some of these patients in a clinical setting, I have had them shadow me during my clinics. My
clinic is mainly traumatic brain injury, the other two psychiatrists do more general practice. Just email me. That’s just extra but I have
had some people ask me that question.
OK, the readings for today’s lecture are again on Blackboard. Since I haven’t heard anything, I am assuming that everything off
blackboard has been downloadable. In the past, it’s been a little shaky but since I haven’t heard anything, I will take it as a sign that
it’s fine. The Cummings article is just a good review article about circuitry, frontal circuitry, it’s kind of based on classic work. I
think it’s a good model for trying to understand the way that the frontal lobe, particularly the pre-frontal lobe, do function. The reality
is that in most diseased states, this is not going to be that clean. But I do think that understanding circuits gives you a better idea of
how things work. It’s a very good article and much of what I talk about is based on circuitry so that reading is directly applicable to
today. I did put an extra reading online. I thought it was very well done and a very good review of frontal type epilepsy. Some of
these, especially behavioral type epilepsies are hard to diagnose and hard to pin down. Sometimes it is very difficult to treat and they
can masquerade as a number of different disorders, particurly other neurobehavioral disorders or psychiatric disorders. So you need to
be aware of them. This is also a very good review article that talks about frontl lobe functions. In general, I think it’s very good, it’s
very readable. I also think it will be very applicable to Dr. Schrift’s lecture because he will talk about the neuropsyhiatric aspects of
epilepsy.
Slide 2
So for today, for those of you who have had neuroanatomy, these first couple slides are just quick review. There are a couple of
anatomical locations when you are just trying to figure out geographically where your frontal lobes are. The central and lateral sulcus,
these are critical landmarks. And essentially, if you remember your neuroanatomy lab, you will remember looking for these
landmarks. Now remember in the frontal cortex, we are looking for a region that is pre-frontal as well as areas that are more involved
in motor, like the supplemental motor area, etc. So for the purpose of our talk, we are more interested in prefrontal cortex.
Slide 3
Another nice picture of your brain, with nice, strange colors. But you can see that it is not very difficult to divide up the lobes. In
terms of functioning, there can be some overlap there. But not very difficult to divide.
Slide 4
The prefrontal cortex, that’s going to be a more anterior section. There are key areas that it’s going to be divided into. Again,
remember that, to some degree, this is our attempt to provide artificial organization to the pre-frontal cortex, it doesn’t always follow
our rules. But in general, we talk about dorsolateral prefrontal section, we talk about orbito-frontal, mesial-prefrontal or cingulate
areas. In terms of circuitry and function, they all have something that is unique from the others. Again in many diseased states, in
trauma, you don’t just affect one circuit or one pre-frontal area. You will see that in some of the examples. But again, it is a good
model to try and understand how this works.
[Inaudible question from the audience, something about the cingulate]
Well they use them interchangeably, when they talk about circuitry. It is not totally the same per se but when you read the Cummings
article, but they will kind of interchangeably talk about it. That’s why this system is useful but if you read other sources, they will
even divide the prefrontal cortex into four areas. It is arbitrary but for our purposes, I am just going by the Cummings article. When
they go through the circuitry, they kind of put those two together. When we talk about the function, hopefully it will hang together
and make some sense.
Slide 5
This is again just putting it on geographic context. The area that we are interested in is the very front area, the anterior pole of the
frontal lobe. Now this is an area, the reason that I am particularly interested in it, is that in traumatic brain injury, my area of
specialty, that is a particularly vulnerable area. Especially acceleration or deceleration incidents because it’s right out there, against
the bone, it is easily contused. It is one of the most commonly contused areas in trauma. We will talk about that more in another
lecture. The reason that it interests neuropsychiatrists is because a lot of modulatio of behavior, mood and cognition take place here.
It’s a pretty critical area. Most of you allegedly have a high-functioning pre-frontal cortex that allows you to do what you do. Don’t
take it for granted when you are playing rugby or butting heads or doing something like that.

Slide 6
So essentially, pre-frontal cortex. Some of this may overlap with neuroanatomy. I know it doesn’t go into a ton of detail but a little
overlap is not so bad, it helps you to remember things. It does play a role in cognition, mood and behavior. The one thing to
remember about the prefrontal cortex (PFC) is that it’s primary role is modulatory. So the functions that it handles also relies on other
areas or circuitry as you will see. But the PFC is very important for modulating, fine-tuning lots of higher functions, particularly
mood and behavior, as well as cognition. So planning complex behaviors, aspects of personality, although it’s not totally seeded
there. We will see that people who have frontal lobes affected by trauma have very significant personality changes. Social behaviors
are modulated here. If you PFC is not working as it should, you might be very inappropriate, even without alcohol. Socially
inappropriate behavior is a common problem if there is injury here. So it has an integrative role, modulating is very important here.
Slide 7
So executive function, I have talked about this term several times already. It really is what it sounds like. This is referring to higher-
order cognitive functions. Now some of this is testable. Dr. Pliskin generally gives you his talk earlier in the year but we had some
scheduling conflicts this year. But he will specifically be covering this and he will be talking about some of the tests that I am going
to mention in this lecture, as well. Some of this execuetive function is directly testable. Some you will acquire by taking a good
history, what a patient is doing in the real world. So for instance, if a patient comes in and there has been some changes that involve
them making poor judgments at work or complaining that they can no longer multi-task at work. So in a sense, what you are getting is
a history of possible execuetive dysfunction. So overall, it’s a lot of factors involved, to have a goal, to work towards it, to show good
judgment in social settings, to account for possible consequences of your actions etc., to predict outcomes, to problem-solve. So all of
these things that we basically take for granted because hopefully, we do these things on a pretty routine basis. All of these things are
pretty heavily seeded in PFC. We rely on it being intact and functioning.
Slide 8
Some of the testable functions, cognitive functions, include working memory. You will hear more about this. This is a very
commonly studied phenomenon in a lot of disorders. This is the analogy that sometimes you are the chalkboard that you have got in
your brain where you might quickly write down phone number and remember it long enough to dial it. Or someone gives you a bunch
of numbers to add up in your head. You need working memory to retain those numbers but you really have no intention of retaining
those numbers in an hour or two. Working memory can provide the template for things to go into longer memory or it can be just
what it sounds like. Working memory, you are just using it like your brain’s blackboard, so to speak, and then you are losing that
information. Again, something that we don’t think about but we have to use all the time. But if you have a mild impairment and you
are an individual in a high functioning position, physician, attorney, somebody who multitasks or manages a business, small
decrements in function here can really impair your ability to do what you need to do. So it’s really very important function because
impairment affects so many broader aspects of function. Verbal and design fluency is also commonly tested and also related to PFC
function. This is the ability to generate a list of words. An example of a task is I am going to give you one minute to think of all the
words that begin with a “f”. Or all the animals that you can think of. This fluency, this ability to generate a list of words based on
some category, is very related to PFC functions. Obviously, other areas of the brain are involved in this because this also involved
language functions. This applies to design as well. They might ask you to draw as many novel designs as you can think of in one
minute. That sort of thing. So maintaining and shifting from one concept to another, let’s see some examples of this, like the strue
(sp?) task where you have to use one concept or idea to solve one problem and then you have to be flexible enough to decide on a new
set of rules. There are examples of these things in the lab, in the neuropsychological test designs. Again, Dr. Plisken will cover that in
more detail. The nice thing about neuropsychological testing is that if there is an impairment in PFC, there is a nice pattern of
impairment that you will see on the testing. In some ways, this makes them more sensitive than some of our images. If testing is done
well, if it is done by someone who is qualified, they can in sum, with pretty good accuracy, this is suggestive of left frontal
dysfunction or right prefrontal dysfunction or there seems to be parietal components etc, there is temporal lobe dysfunction etc. So
they can look at it and give you a pretty good idea of functionally mapping out the brain. Just from these tests, it’s not perfect science
but it’s very good. So the PFC also has a role in focus and attention. To some extent, that’s more of a modulatory role but when your
focus and attention are very impaired, obviously that’s also going to affect working memory and longer term memory etc. None of
these things are very distinct but they are all interrelated and interdependent for you to function all the ways that you do.
Slide 9
Now, frontal lobe syndrome is a term that is still actually used because clinically it is very useful. So they say prefrontal syndrome but
they basically refer to cognition, mood and behavior dysfunction that follow damage to prefrontal cortex. And it is useful, it is a loose
term, not easily quantifiable or qualifiable in some ways. But clinically, it is useful. And if I use it, I can still be more specific in what
I mean. For example, if I say a patient is disinhibited or inappropriate or inattentive, I will say that. I won’t just say frontal lobe
syndrome. Or I might have a patient that’s apathetic and inert, slow to start things. That’s another of PFC dysfunction. I will
describe that.
Slide 10
So a little bit more specific about things that could be impaired. We talked about execuetive dysfunction that you could see, the
functioning that is very reliant upon PFC being intact. Behavior changes, there is quite a range that you can see with PFC dysfunction,
which in some ways, leads to it being misdiagnosed or misunderstood. People can look depressed with PFC dysfunction, they can

look manicky or hypo-manic. From the first lecture, we talked about one of the great pretenders of patients who come in with manic
behavior. It can represent so many different things, not necessarily a primary psychiatric disorder of bipolar. Certainly, in the
differential but there is a number of different things that can masquerade as that. PFC dysfunction is one of those things. But you can
see that there is a range here. You can have someone who is distractable, disinhibited, irritable, manicky but you can also have
someone who is very apathetic, slow to respond, inert. They can almost look depressed, they go so slow. That’s where the different
circuitry comes into the PFC. Mood disorders also. We know that the PFC plays a significant role here. It’s probably not studied as
well as it should be, compared to primary mood disorders. But we do know that there is a strong connection here. We do know that if
there is PFC dysfunction, it can either aggravate or cause a type of mood disturbance or you can see a mood dysregulation, where a
person is almost going back to like when you were two years old, where you react first and you think second. So for instance, you are
not as good at filtering things out. The environment affects you very strongly. Something good happens and you jump up and down.
Something bad happens and you won’t come out of your room for a week. Sometimes, responses can be very extreme with this
dysregulation because all those abilities that we have built up in our frontal lobes that allow us to temper our responses to our
environment. So we don’t have all these extremes, we don’t feel like a human yo-yo. This can happen if we have disruption of
function here.
[inaudible question]
To some degree, yes. That’s usually picked up on the cognitive testing and I am going to get to that. But we are going to focus on
talking more about circuitry right now.
Slide 11
What are the causes of PFC dysfunction? Again, going back to previous lecture. How can you have dysfunction in the brain in
general. You can have direct lesions or indirect dysfunction due to damage in other parts of the circuit. You can also have
dysfunction due to damage in the circuitry itself. In other words, white matter or tracts are damaged. You can have electrical
abnormalities such as seizure disorders. Actually we take it for granted that when we think of seizures, you always think of
convulsive or motor seizures. But if you think about the brain and how much of the brain manages non-motor behavior and how much
of the brain is dedicated to neurobehavioral function. The fact is those areas of the brain also tend to more sensitive to things such as
oxygen deprivation or types of trauma or strokes. Then it starts to make sense. Your seizure disorders could present as
neurobehavioral changes. We are more used to thinking of motor seizures but really not the significant bulk of seizure types that we
see. Neurobehavioral seizures are harder to pin down, harder to diagnose and unfortunately, sometimes harder to treat.
Slide 12
There are certain neurotransmitters (NTs) that we know are key to PFC dysfunction. So this kind of gets into chemical, metabolic
ways that the brain might become dysfunctional. Perhaps, pathologically, it looks intact but if you have disruption of NTs, you will
see certain types of dysfunction. And that’s what we think of in certain types of disorders. There is not only structural damage, there
is also a disruption of NT systems, they don’t function the way that they should. They are either hyperactive or hypoactive. In
different diseased states and in trauma, such as TBI, generally involves several of these mechanisms. There can be structural damage,
there can be dysfunction chemically or neuro-transmitter wise and all of this can be contributing to the clinical picture. And all of
these aspects, understanding all of them, gives you a rationale for where you want to target when you treat the patient. So if you have
an understanding that something looks frontal, and you think about the things that cause that, it’s going to lend itself to making
rational decisions about treatment or give you research ideas about treatment. It’s an intervetion point. So if you think there is a
disruption in a NT system, hypo-dominageric states, at times can lead to symptoms that look rather pre-frontal. You might think why
don’t I enhance dopamine. It’s sort of a simple example but it does lend you to making rational decisions about possible treatments or
interventions that you might want to study. We will talk about this in another lecture as well. But I wanted to talk about it here
because it is a critical component of proper functioning of PFC.
Slide 14
Key points again. Circuitry is a good model for understanding neuroanatomy functional relationships but you have to keep in mind,
it’s a nice model, I think it’s a good way to understand the trees before the forest, so you get a good sense of things. But again, I
always stress that many disorders will affect a number of different aspects, that ultimately show you that the PFC is dysfunctional.
Rarely, do you get a disorder where you can say this is just a dorsolateral PFC dysfunction. We have nothing that specific. But again
it is a good model for understanding how it works and how it overlaps and how all the different subsections complement each other.
Slide 15
So the cummings article. It’s based on work that a number of other authors have contributed to. It’s very elegant work that looked at
all of these circuits. This is relatively new work. It wasn’t that long ago that we used to think that if you damage the cortex, you get
the dysfunction. Before we used to think of the brain as discrete areas and damage in these discrete areas causes dysfunction, which it
can. But now we think more in terms of networks. Much more than we will say this is a parietal function, we will say this is a parieto-
occipital circuit. This is very elegant work that was done. They described essentially five frontal-subcortical circuits. They are
parallel but they are independent and they are closed. They are loops, so to speak. They are named after their function or their site of
origin in the cortex. Two of these are motor circuits that arise from the supplemental motor area. They are heavily involved in
oculomotor testing. And if anyone remembers some of the slides that I showed, fMRI. I showed a fMRI image of using oculomotor

testing as a way of probing PFC. We are not going talk about the motor circuits but just be aware of them. We are going to focus on
the neurobehavior circuits. Basically, there are three, the dorsolateral prefrontal, orbital frontal and the medial frontal circuit, which is
also interchangeable with anterior cingulate. You will see how they have some commonalities and some differences.
Slide 16
The common features of these circuits. So for all of these circuits, damaging common areas can damage circuits in all of them.
Basically all these circuits originate in the frontal lobe area. They have specific projections to striatal areas, from there to globus
pallidus, to the thalamus and then back to the prefrontal area of origin. This creates a closed loop. There are also open loops that we
are not going to talk about in great detail. But these are other types of pathways or circuits that modulate these systems that are open.
In other words, they are not closed systems.
Slide 17
This is a schematic for these common model, these closed circuits. Frontal cortex, striatum, globus pallidus, substantia nigra in that
area, the thalamus, back to the frontal cortex. So again back to what I mentioned in an earlier lecture. Remember I talked about
strategic placed lesions. Location, location, location. So if you have a lesion in a certain area of the thalamus, like the dorsomedial
thalamus, for example, because that has a lot of connections to the pre-frontal cortex, you will see frontal cortex like symptoms. There
doesn’t have to be direct damage to PFC but if you have damage or dysfunction in a key area, the patient can have that type of
presentation.
Slide 18
We won’t spend a lot of time here. I just want to make the point here that there are some open connections. For instance, dorso-
lateral PFC has some connections with the parietal lobe etc. , things that moderate the function. These things work together and they
allow proper functioning of that circuit.
Slide 19
So here are the circuits for our purposes. Dorsolateral prefrontal cotex, this circuit is one that we classically refer to as being
cognitive. None of these circuits are exclusively cognition, exclusively mood or exclusively behavior. So This is very easily tested,
as someone like Dr. Plisken will do. Very heavily cognitive, you can see some behavioral and mood changes here. In contrast to that,
lateral orbital or orbitofrontal cortex, we think of this as having more behavioral or mood consequences when there is damage or
dysfunction here. The model that is often used or the expression often used is that you will talk about patients who are
pseudopsychopathic or psychopathic or look anti-social. A number of terms apply. The reason that is used is that these are patients
that seem to have significant changes in personality and behavior, inappropriate social behavior, difficulty understanding
consequences for their actions. So they look a bit sociopathic. But it is due to some lesion or dysfunction as opposed to someone who
have might have been like this their whole life, which in psychiatry, they refer to this as character disorder. And it’s hard to know
what the involvement of this is, in long term character disorders because there are so many similarities to people with acquired lesions
here. It can look like these long-standing anti-social personality types. You just wonder how people developed those character
disorders in the first place. So lesion models, at least allow you to pinpoint if the person was functioning fine beforehand. It allows
you to make some assumptions about neuroanatomy functional relationships. The other circuit, medial frontal, or sometimes referred
to as anterior cingulate cortex circuit, is more involved with apathy, motivation and drive. So patients with damage or dysfunction
here can look very apathetic and amotivational. At the most extreme, patients seem akinetic or mute, waking and alert but not really
responding well, not doing too much, sometimes referred to pseudo-depression. These patients can seem very slow, psycho-motor
retarded and they will look depressed. But interestingly, they may not report depressed mood. They may not feel sad but they have all
the other features that can make them appear depressed. And the treatment can be different so it might be difficult, not to be confused
with the fact that young patients and elderly patients sometimes don’t acknowledge that primary depression is a sad mood. That just
makes things a little complex. So sometimes, this can get a little tricky. People with genuine depression may not acknowledge sad
mood. But all these other features are here to suggest depression. For young children who are depressed, not uncommonly instead of
crying and telling you that they are sad, they will act out. So if you are going into child psychiatry, you will have your hands full
trying to figure that business out. And sometimes, I think medically ill or elderly patients, there can be a depression that they may not
acknowledge as a sad mood. So, it can get a little difficult to sort out.
Slide 20
So, dorsolateral PFC syndrome. What would you expect to see if your primary dysfunction is in this area. Based on what I have said,
you would see a lot of cognitive execuetive dysfunction, that is usually very testable. So these people are not very hard to sort out, to
get the appropriate evaluation. A lot of problems with impaired reasoning, mental flexibility, maintaining and redirecting attention.
You can see attentional problems with PFC dysfunction. Examples of tests that test classic PFC tasks are Wisconsin Card Sorting,
you will hear more about it, and Trail B, again you will hear more about it. It is not so important to rememeber how you do these tests
or how to score these but just to remember that these are classic tests that are generally associated with PFC function. But the reality
is that it can get a little dirty. There is really no such thing as as a pure PFC test. However, we know from studies that have been done,
lesions, model etc., that the PFC is very heavily involved in these tests. So when there is an impairment here, we are relatively safe in
saying that there is a PFC dysfunction. Other parts of the brain may be involved. The bottom line is these tests are very heavily

weighed towards PFC function. Verbal and design fluency, again this is something that is not too difficult to test, and it reflects
dysfunction here.
Slide 21
Conversely, orbitofrontal syndrome patients may not look so bad on cognitive testing. That’s one of the key things to keep in mind
here. PFC syndromes don’t look all the same and you don’t evaluate them all the same. So some of these patients may not show
deficits on some of these classical tests that we do. Their behavioral disturbances are the key features here. Disinhibition, for
example. Emotional disability. The classic case of Phineas Gage is an example. We will talk about that a little bit later. Damage here
can cause significant personality changes. And if you didn’t know how a person was originally, you might assume that they are very
difficult and annoying and irritating. Since these are being videotapes or audiotaped, I have to be very careful of what I am saying.
But very difficult people here, if you didn’t know how they were functioning before the injury or the diseased state. So unlike
dorsolateral lesions, they may be able to do the card sorting, they may be able to do the Wisconsin card sorting. So these are the
patients that I think can be mistakenly diagnosed with other disorders, like primary psych disorders. Because they can look
disinhibited, they can look hypo-manic. But if you take a good history, you are not going to make a mistake. But I have seen some of
my head patients mislabelled as bipolar. The problem is that if they get mislabelled, sometimes the treatment is not appropriate. So
they may have features in common with it but it’s not the same thing. And you have to be careful to make that distinction. Or at least,
know when to consult someone who can tell the difference. So if you have a high index of suspicion and you are looking at other
possibilities, you are going to pursue other avenues. You are not just going to accept that if a patient comes to the emergency room,
they are psychiatric when they are not.
Slide 22
Anterior cingulate are the mesial type syndrome. The cingulate has been studied a lot in regards to apathy and motivation, that sort of
thing. This is an important part of the PFC circuitry here. One of the primary behavior manifestations is lack of motivation. Patients
that have dysfunction here can look very amotivated. And everything exists on a spectrum, from mildly impaired to greatly impaired.
In this syndrome, the extreme version is the akinetic mute. This is rare in reality, you would need bilateral lesions of the system. They
can look wakeful but they are indifferent, apathetic, they are not very responsive. The milder version of this, what I often see with my
TBI patients, is they don’t care about things too much anymore, they will tell you that. Again, you need to be careful here because
you might think they are depressed. They might be but we also know that PFC dysfunction will cause them to lose motivation and
drive in varying degrees while at work or school, they might just be labeled as being difficult or not trying hard enough. You might
see how on the mild end of the spectrum, we might just brush this off as and think that the patient has more control over it than they
actually do. Neuroyschological deficits you may see here. They are more subtle as well. I am going to defer to Dr. Plisken and ask
him to make sure and cover this. But again, history and behavioral and mood disturbances will help you to make the diagnosis. These
patients can show some impairment under psych testing but again not going to be the classic signs that you see with dorsolateral PFC.
There are go/no-go tests that test response inhibition. They may do poorly on those. Overall, broad difficulty understanding new
thoughts, participating in creatve thought processes. This is not very easily testable. Again, you might get in the history that this
person had a change in function that is consistent with this. You might have family members or someone else to tell you how they
were like before. Very important that you get this history beforehand to make sure that you are not missing anything. And apathy
does occur in wide variety of disorders. By itself, it doesn’t help you to localize the lesion. People have tried to work directly with
apathy. My feeling is that is too broad. Because you can have apathy with somebody being primarily depressed, someone with PFC
dysfunction, they can look apathetic. There are certain subcortical diseases that make people seem apathetic, again because of that
construction of cortical-subcortical circuitry. Parkinson’s, Huntington’s Disease, diseases that we think of as subcortical processes,
can look frontal because these circuits depend on various subcortical aras of the brain.
Slide 23
So some specific causes, to make this clinically practical. Stroke, either directly involved in the PFC or indirectly by involving the
circuitry. Examples we use are basal ganglia or thalamic infarct and cause certain types of cognitive impairments and they can look
prefrontal. But the good news about these thalamic cognitive syndromes is that there is often very good recovery, if that is the only
area involved. Tumors and AVMs, depending on where they are located and where they are impairing structurally, can present this
way. Degnerative diseases, we will talk about these a little more because I think they are a good example of someone presenting
clinically where you may make mistakes about what is initially going on with them. TBIs, another good example of patients who can
look personality altered, mood dysregulated etc. so that unless you have a good history of the injury, you can miss. We will go over
that more in another lecture. [inaudible question]. Oh, I am sorry, arterio-venous malformations, just so you see some abbreviations.
Also, PFC dysfunction is studied in regards to its role in primary psychiatric disorders. That makes a lot of sense right? It makes sense
that people with schizophrenia, obsessive-compulsive disorder may have some dysfunction in these regions, in these circuits, although
it may be because of developmental or genetic reasons. These areas make sense as targets for a number of different disorders. These
acquired disorders actually allow us to study them more clearly. People who were functioning fine getting strokes ot traumas in these
regions and then you can kind of look at before and after and say this makes sense in light of the regions where we the lesion or the
dysfunction. And seizure disorders, last but not least, the great imitators in the way that they present. And Dr. Schrift will talk about
those in greater detail.
Slide 24

Brain injury in general can disrupt circuits. Brain injury can be due to a number of causes, that’s just a loose term. Stroke is a type of
brain injury, right? TBI, usually from an external source such as you are struck in head with bat or during car accident.
Slide 25
Let me talk a little bit about dementia. Extremely common disorder. You will see this unless you go into Peds and then you will see
parents or grandparents with this. Very hard to avoid this. These are patients that you are going to see clinically, in a variety of
different settings. Primarily for a dementia work-up or they are being seen for other medical problems or surgeries and they have an
early type or already diagnosed type of early dementia. And depending on how these things present, they can represent different
degnerative processes. It can show you clinically how it looks to have varying degrees of PFC involvement. Alzheimer’s disease,
Fronto-temporal dementias, there are different classification systems for those. For fronto-temporal dementias, we don’t need to go
into great detail but I think the primary concept is that this is a group of dementias where the primary feature is that the frontal cortex
is more involved or where the fronto-temporal cortex is more involved. Vascular dementia, that’s going to have a variable presentation
depending on where the primary location is. If it is a multi-infarct dementia, it’s going to depend on where the infarct is. The more
gradual type of vascular dementia, that is going to occur over time if you have hypertension or diabetes and you don’t have an
identified stroke but you have an ischemic changes over time. As a result, there can be mood or behavioral changes. We used an
example in a past lecture where someone may present looking weepy, depressed and distractable as a manifestation of them having a
type of vascular dementia.
Slide 26
Subcortical dementia. We think of Parkinson’s Disease or Huntington’s Disease as primarily subcortical diseases. Certainly, motor
manifestations are subcortical. But these patietnts, either early on or eventually, will show some degree of PFC dysfunction. It is not
unusual for Parkinson to have as one its earlier presentations either a mood disorder or some mild behavioral changes etc. And you
have to be an alert clinician as you examine your patients. You might miss the early cogwheeling if you see the mood disorder or
depression present. For a number of these neurodegenerative processes, they can present neuro-behaviorally. You need to think of it
as all part of a neurological exam and you have to consider all of this when you are localizing the lesion. It just gets more difficult as
you talk about higher functions, like neurobehavioral functions. But it’s no less important than demonstrating that they have right side
hemiparesis, that’s just easier. You are not going to miss that but people are going to miss the neurobehavioral manifestations of these
disorders.
Slide 28
So let me give you some case examples. The classic case, the one that everyone has heard of, is Gage. The interesting thing about this
case is that allowed scientists, at that time, to study a discrete lesion that was more mesial and orbito-frontal of the PFC, that
behavioral and personality part that I talked about. The guy lived, God knows how, with the instances of infection. This was a rod that
went through his head and he was completely different afterwards. We don’t see these projectile lesions very much these days, it’s
very rare. With all of our TBIs now, most of them are very diffuse or dirty injuries, acceleration, deceleration accidents, motor vehicle
accidents, falls etc., the occasional gunshot wound. Very rarely, do we actually see a projectory so that we can actually look at the
path of whatever damaged the brain and make some conclusions. So, Gage inadvertently became a type of case report but people
learned a lot from studying him. It’s just really amazing that he lived. But his primary features were his behavioral and personality
changes. He became very difficult. I have heard different stories about what happened long term. He was no longer Gage. One of the
things that you will hear from family members of patients who have this type of PFC involvement, irregardless of whether it’s due to
dementia or TBI or tumor or AVM, is that they will tell you that the patient is no longer the same person. I hear this so often in my
TBI clinic, even with post-concussive syndromes, allegedly mild injuries. So you see again that with strategic lesions, it doesn’t have
to be a big or grand lesion, but when you disrupt key functions of PFC, you can alter the basics, the way that some people come across
to other people, personality. These families will say, “they don’t seem like the same person” and that’s always a red flag. Of course,
they could be sustance abusing as well. You don’t rule out other things that alter presentation and behavior but that’s really one of the
things that you hear and it clues you into the things that could be going on.
Slide 29
Here is a picture that I found of the trajectory. And the rod that was driven through his skull came out clean the other side. And the
guy lived. But like I said, given the area, there was more of a behavioral and personality presentation. This was a historic case
example.
Slide 30
Now what we see are usually diffuse injuries of the PFC and also in other areas of the brain. So it’s never this neat. So here is an
example that should sound a little similar to some the ones that we have talked about. A 60 year old gentleman comes in, he has a
history of progressive change over several years, we are not talking about anything abrupt. But the family has noticed that he has
become more disinhibited, he swears now, he throws things and they say, the classic thing, “he is not like how he used to be, he is
different now”. And at times, he is socially inappropriate, sometimes he seems apathetic and unmotivated. Very significant mood and
behavioral changes are the family’s key concerns here. They are not coming in and saying: “Gee, his working memory doesn’t seem
like how it was before”.

Slide 31
So you send them to someone like Dr. Plisken, who does cognitive testing and it shows that he is relatively intact, in terms of his
memory. Visual and spatial abilities seem OK but he is kind of slow, he is kind of perserverative. This is very common in the
presentation of some prefrontal patients, they get very stuck in set, very perserverative, have difficulty getting off or letting go of
things, getting stuck on things. Perserveration, although it can be due to a number of things, is not uncommon in PFC dysfunction. He
also has a short fuse, gets very impatient when you try and test him. This is a patient that you would expect to be very difficult after
four or five hours of testing. …
Slide 32
This can be a case of fronto-temporal dementia [49:44]. These are people who present with more than behavioral mood alterations. So
you might be thinking, this is an older gentleman, he is getting difficult, maybe he is just depressed. And he might get better with
medication, he might look better. Maybe you sprinkled a little water on the fire but you didn’t make the correct diagnosis. This is
pretty classic and very extreme where there is this selective fronto-temporal involvement on this MRI where this is getting back to
your normal aging brain. And the asymmetry here, almost nobody looks really straight. There is almost always a little tilt, you will
see a little asymmetry. So this normal person really doesn’t these terribly asymmetric ventricles, they are just a little rotated. This is
classic, it is relatively extreme but it’s classic. It shows you that there is clearly this predilection for involvement in the fronto-
temporal area, as opposed to other areas of the brain. Is this T1 or T2? T2.
Slide 33
So as I mentioned, in fronto-temporal dementia, there is a lot of different sub-categories of people to look at. So in the olden days, we
used to just talk about Pick’s Disease, because there were certain types of inclusion bodies that you were able to see. But for our
purposes, it is just important to know that this is a type of dementia and once you have identified it, you can figure out which one it is,
whether it is fronto-temporal dementia or something else. Many of the specific diagnoses can’t be made until you do a pathological
exam. But you can diagnose a fronto-temporal or frontal type of dementia. And this is probably estimated to upwards of 20% of
degenerative dementias. Maybe more, because as I said, these patients can be misdiagnosed initially, it’s not always pickes up on.
Slide 35
And this is just re-iterating what we covered. And just to make the point again that neuropsychological testing results in fronto-
temporal dementia are going to be variable. If you catch someone early on, they might not look so bad on testing but their behavior
during the testing may be more obvious. You know, they are irritable, they are impatient, they are amotivational, they don’t do what
you want them to do. For example, if they show some memory problems but you cue them by giving them a list of words that they
can recognize, they may do better with that. Whereas in an Alzheimer’s patient, they just don’t remember it, they don’t store it. So
even if you cue them, theoretically it shouldn’t help them that much. Frontal-type or these subcortical type dementias, sometimes will
show these modifications of memory impairment, something Dr. Plisken will talk about a little more.
Slide 36/37/38
Let me just move through some of these other examples. 72 year old woman with relatively negative past medical history, she is
pretty healthy. The family brings her in and the primary complaint is gradual onset of problems with memory. Again, these are
examples that are relatively clean and obvious. If you are lucky in your clinical careers, you will see one or two classic cases.
Everything is usually complicated by so many other things. But again, she has this gradual onset of memory problems, trouble with
names, where she put things etc. So this wouldn’t be so hard if this person was brought in. So the primary complaint is that she has
memory problems so lots of people will be thinking, “oh she has alzheimer’s”. But they are denying that she has changed in other
ways, she might be a little sad, she is really still herself. So relatively classic Alzheimer’s. If you look at the parietal sulci, they look
widened. But here is the point that I am making, the PFC doesn’t look so bad. There is some atrophy there but as opposed to the
fronto-temporal dementia slide that I showed you earlier, the pathology here involves more other areas. So this is a relative sparing of
the frontal areas and it’s more this inferior parietal lobule, which you will see in the imaging of some Alzheimer’s patients. Now when
this disorder progresses far enough, everything gets involved. As the disease spreads, it is going to affect circuits. But early on,
relative sparing of frontal type features. So this is the type of dementia that you are not going to be so suspicious that it’s there because
they present with memory complaints. So two examples of degenerative diseases, both involve PFC but at different points in the
disease process, which makes it important to be aware of this, so you don’t miss early manifestations of frontal type dementias. Also
be aware that Alzheimer’s, at certain points, can look relatively frontal when it’s more impaired.
Slide 39
This is another case that I mentioned before. Remember the young man with the TBI and remember that I showed you that MRI scan.
He nearly had some left frontal involvement. I will talk about it later. But again, a good example to keep in mind because these
patients are going to come to the ER or they are going to wind up in a neurology or psychology clinic because of behavioral and mood
changes.

Brain and Behavior: Traumatic Brain Injury
Announcements:
Lecture Content
So today we get to talk about the topic that is nearest and dearest to my heart. It has been my area of expertise for at least 20 years
now, traumatic brain injury. There are a couple reasons why it is useful for you to know about this, not only is it a very common
problem it is also a good model for understanding neuroanatomy functional relationships. Much of what we talk about in terms of
treatment in chronic TBI and behavioral disorders will also generalize to patients with disorders due to stroke, other types of trauma,
and even some disease states. The reading I suggest for this is a book chapter so it is pretty thick but it is very good and very up to
date. Also some of these slides have been updated since yesterday so make sure you have the updated ones. When I talk about
traumatic brain injury I’m talking about a non-degenerative, non-congenital injury that’s due to external force. Classic example would
be a motor vehicle accident or a baseball bat to the head. There’s different categories like closed head injury and penetrating head
injuries. Most cases are closed head injury; even severe injuries can still be closed head. There is no breech of the skull and the injury
occurs from the mechanical trauma that occurs.
Clinical severity of TBI. This is what you will see being used in an acute triage situation to discern which injuries are most
important early on. You want to sort out who is a medical and neurological emergency. If it is followed by a decreased loss of
consciousness, decreased respirations or a bleed then it is more of an emergency. Very few mild head injuries are emergencies, it
doesn’t mean they don’t have consequence but we just don’t treat them as emergencies. The rough scale that is used is based on
several factors. You will see the Glascow coma scale (GCS) in all trauma patients when you rotate through the emergency room. It is
just a rough scale designed to measure level of alertness, so if they are in a coma, how deep is the coma. There is a copy of the scale
on the next slide if you're interested but the general take home from this is that it is a scale up to 15 with 15 being most of us in this
room, fully conscious. Then depending on certain tests of eye opening, motor response, response to verbal cues, if you call their name
do they respond etc. It is a nice scale to use acutely and also to monitor someone's progression overtime. It really isn't used for
chronic patients obviously. There is a general breakdown, most of the time they consider milder injuries those where the GCS is 13 to
15. The trouble with the GCS is it depends on who administers it and when they administer it. Early on it if you get to someone in the
field who has a traumatic brain injury they may not have become unconscious yet; similarly, if you don't measure them until they
come into the emergency room they could be worse or better than they were initially. It is still good for acute patients. Posttraumatic
amnesia is a bit tricky because most clinical settings don't do a formal measurement and what they're talking about for PTA is
anterograde amnesia, so if you got knocked on the head and you were out of it for 15 minutes and you look back and you don't
remember much from the 15 minutes, and during the 15 minutes you may have been repeating yourself and asking where you are etc.
You were in posttraumatic amnesia. So you are awake but you're not able to store new memories. Or you are just not able to keep
track of things. So the rough guideline is when somebody comes out of that state PTA is resolved. Obviously if someone is comatose
you can’t really include that in the duration of PTA, and that is where it becomes a little tricky. Also in hindsight with most mild
injuries nobody was around you can't get an estimate of PTA, they may not even be able to tell you if they lost consciousness or not.
If you are off by yourself riding a bike on a trail and go over the handlebars and you come to you have fallen and you hit your head,
you might not be sure if you were really knocked out or just dazed etc. So these measurements are good but they're not always perfect
and they are difficult to obtain. In general the old rule of thumb was that a mild injury did not have findings on a standard clinical
imaging exam. When they did CT scans acutely in an emergency room and they saw something on CT a mild head injury was
bumped up a grade. They were trying to base severity on acute image findings. Now we know imaging varies so much from center to
center. But in general the rule of thumb is if you find something on a scan acutely it is more severe than just an uncomplicated mild
injury. This modifies overtime as imaging does improve. If you remember from previous lecture of DTI, even mild head injuries
showed decrease in white matter. So it is not that they don't have changes it is just that imaging used in emergency protocol may not
pick up these changes. So this is just a copy of the GCS for your own reference.
What is a mild DTI? This is one of the areas that I think is most tricky. This is by far the most common group, it accounts
for 80% of all traumatic brain injuries. It is probably under reported because a lot of people in sports or other activities can actually be
concussed but they think they are ok so it never gets reported. Even if you’ve had an uncomplicated mild head injury you probably
recovered very well with no residual effects, but like I said that doesn’t mean there weren’t changes. So this makes it difficult to
diagnose because if you look at this criteria it actually sort of fits everyone here because you are basically saying it is manifested by
any period of loss of consciousness, any loss of memory of events, any alteration of mental status, you can have a normal neurological
exam with a mild injury, etc. There’s other criterion for mild head injury. Some research studies will require a documented loss of
consciousness just to have some kind of clear cut off but if you remember what I said some times it is difficult to determine if there
was a loss of consciousness and how long it was. So these papers that I read look at chronic TBI subjects and report that they know the
average loss of consciousness, my question is always where they get this info. That’s something to keep in mind. So this is why
clinically mild head injury has been difficult. We don’t know where the cut off for no head injury and enough head injury to sustain
change and enough head injury to sustain clinically observable change is. You can have neuropathology with no loss of consciousness.
We are trying to sort out where the threshold is when that neuropathology can be clinically observed.

Traumatic brain injury is a huge public heath problem and very common. It can be a problem in how it is approached
medically because it falls in so many different domains. The majority of these injuries falls in the mild category and is often
overlooked. It is a significant cause of long term disability because the population most affected is generally younger people,
otherwise healthy. If you suffer a head injury you can go living a long life but with persistent disability. There are of lot of specialties
that deal with TBI, I’m a little bit rare in that I am a neuropsychiatrist who focuses on traumatic brain injury, but it tends to be a bit
scattered. When an individual wants to seek treatment for consistent problems, they are not sure where to go initially.
Again mild head injury is by far the most common problem. Even though it is called mild it can leave you with some
permanent neuropathic changes that can predispose you to future difficulties or problems. Repeat head injuries, like in a number of
athletes who have just been “dinged”, but a number of times to point where they don’t remember their wife’s name or they have to
become sports broadcasters because they can’t play ball anymore. It’s very common and this is the first time I have seen where
athletes will actually admit to that. As an athlete you are not going to say you felt funny after an injury, you are going to say you are
fine because your goal is to get back into the game, they have anti-malingering problems so the bias is the other way. But sports
injuries are coming to the forefront now and are given more importance as they should be.
Also another problem we have now that we have completely created is blast injuries. It is something that would not occur in
nature unless you were near a volcano that erupted, so they are sadly a human created form of injury and it is causing a huge problem.
Mostly what I see are motor vehicle accidents but I am getting more calls and emails from family and from veterans that are coming
back and have persistent problems consistent with head injury. Be aware of these because this is something that I think is going to be
persistent, long-term residual because blast injuries can be more severe. So they feel that 25% of bomb blast survivors are suffering
from TBI, it is not well studied so this is probably the tip of the iceberg. These IEDs are to blame and part of the issue now is body
armor is much improved so rather than dying from blast injuries you can protect the body but not the brain. They are trying to study
this in animal research because it seems to have things in common with civilian head injuries like motor vehicle accidents, but there
are some differences that will need to be considered with treatment. It is this primary blast injury that seems to be the difference, that’s
the injury that seems to be the direct result of this wave induced change in atmospheric pressure, we are just starting to understand and
do research on that. Secondary and tertiary blast injuries are when something flies and hits your head or you are tossed and you hit
your head. That type is the type you see similar to motor vehicle accidents. It has been something newer in the news, but that’s sad
because it has been around for a while. You’d be surprised how much media and popularity plays in getting funding for research. So
Bob Woodruff suffered a blast injury and now there is a Bob Woodruff family traumatic brain injury fund.
Another case that probably helped get exposure was probably Andre Waters, former pro football player, had multiple head
injuries. In his forties he had a lot of problems with depression and probably other problems as well. He was having a lot of difficulties
and he ended up committing suicide. I don’t think at the time anyone really related it to the injuries but Chris Nowinski who was a
former Harvard football player and had a number of concussions went on to do wrestling and he understood very well the issue of
sports concussions went under recognized. He had himself had problems from his injuries. He went to the family of Waters and asked
that an autopsy be done. He looked at Andre Waters’s brain and it did not look like the brain of a 40yr old man, it had significant
evidence and pathology of multiple past brain injuries. They also saw the same type of plaques from Alzheimer’s in Waters brain from
TBI. This is one of the reasons they talk about brain injury being a risk factor for degenerative diseases. So it was seen as an important
problem and now there are requests for research proposals to fund this.
When we talk about the neuropathology of TBI we talk about primary and secondary injuries. Primary injuries are as a direct
result of mechanical trauma like if you contuse an area of your brain. Diffuse neuronal injury like I showed you in the DTI lecture is a
very common finding in TBI. That is also considered a primary injury because it is a process initiated by the injury or mechanical
trauma. The part of the brain most vulnerable is the anterior frontal lobes of the brain and the anterior temporal cortex. Those two
areas of the brain are sitting against bony prominences so if there is an acceleration/deceleration course they are very likely to strike
the skull. If you remember the last lecture where I talk about neurobehavioral problems, dysfunction of prefrontal cortex and anterior
temporal lobes underlie a lot of disturbances in mood, behavior, cognition, regulation of mood, features of temperament, personality,
etc. Often these patients are ok and walking around with no observable lesion but the primary problems are the neurobehavioral
deficits.
Just to clarify a couple definitions. A concussion is a physiologic process that occurs with the blow that produces this
observable altered level of consciousness. This is a physiologic, metabolic type disturbance, it can be transient, and it is due to the
blow. It is an event that produces something observable. So it’s not a lesion you see. The contusion is something you can
pathologically see, like a bruise of the brain. You can get coup and contrecoup-contusions. What it is saying is that you don’t just get a
contusion at the site of impact; you can get a contusion opposite that. It has to do with the biomechanics of the injury.
Just to reinforce this, this is what an acute contusion looks like and obviously this person didn’t do so well. As you can see
there’s blood and a lesion, so it is observable damage. Although significant, what is more significant as far as I am concerned, or can
be more overlooked is the effect of diffuse axonal injury on a person’s outcome after TBI. It is also called traumatic axonal injury. It’s
talking about the mechanical force from the impact setting up a process in the bundles of white matter that leads to degeneration and
destruction that translates into abnormalities we can pick up on DTI from the previous lecture. You don’t need direct impact to the

head; for example shaken baby syndrome. If severe enough it can result in death. In general the model that is used is with severity the
involvement gets deeper. So we expect more superficial or more cortical effects with milder injury. We think severer injuries involve
structures as deep as brain stem, in general. It’s a result of a progressive process and less likely to be a mechanical sheering of the
white matter. This acceleration/deceleration process on the axon actually induces a number of changes to disturb it metabolically,
there’s calcium influx etc. this process can occur over short or long periods of time and the final result can take some time to
complete. What this tells us is there are a number of points where we can potentially intervene. In terms of research we can use this.
It’s a process.
The disturbance is set up by the initial trauma but it can take hours to days for the damage to occur. Not all the white matter
tracts respond the same; some will degenerate and become dysfunctional others will actually show some repair processes. Different
axons are at different stages of this process. One of the basic things we know about cell death is that calcium influx is bad and this can
occur secondary to mechanical trauma. Again diffuse axonal injury is important because it may be one of the few pathological
findings in mild head injury. It also may not be visible in standard scanning may need to use something like DTI to really assess white
matter changes. Like I said if you interrupt the cables and connections you can have problems even if the primary areas aren't
damaged or contused.
Secondary mechanisms are possible if injury is at a point where we may be able to intervene. Once someone has had the
trauma you can’t go back and reverse that, but the trauma sets up a number of events. So in some ways the axonal injury gives you a
cascade of events and therefore an opportunity to intervene. There are also things set in place secondary to the trauma that also
contribute to the amount of injury you end up with, so if you intervene you can stop some damage. One of the better studied aspects of
this is excitatory amino acids. Glutamate and Aspartate serve a normal role under normal circumstances, but in trauma for whatever
reason, they are released in excess and become neurotoxic producing damage. This occurs in stroke as well. Also they think low level
excitatory levels play a role in neurodegenerative damage like Alzheimer's. I won't talk about all of these but again there is a variety of
events that still occur so it's not a done deal with the trauma itself. Acetylcholine seems to be elevated after trauma and appears to be
neurotoxic as well. You can have intercranial pressure and edema that causes secondary tissue damage. Also bleeds, subdural
hematomas are not uncommon in TBI.
I sort of covered this but again this area is of interest because it is a potential step we can intervene at. There has been a lot of
work trying to look at the possibility of using glutamate type receptors to use agents that might block of modify, thinking that it may
reduce secondary causes of damage
I’ve mentioned that these bleeds can be a significant source of the trauma before. Subdural hematomas can either be acute
and be a medical emergency, or not noticed early and gradual, and even some cases a chronic subdural hematoma. Here is picture
showing you a very obvious subdural hematoma and pointing out where that occurs.
Let me spend a little time talking about the neurobehavioral sequelae of TBI. There is the issue of acute treatment. If
someone comes in they are going to need to be evaluated to see if they need acute care. More of the severe injuries are going to need
to be admitted to the hospital and can be very complicated. Milder injuries, if they come to the emergency room are rarely kept in the
emergency room. We are more interested in what happens after the acute event and the problems that arise. We talked about the
changes with disturbances in frontal and temporal lobes but also white matter disruption can aggregate frontal dysfunction. That’s why
the disabilities you see after TBI are not going to be the motor complaints like after stoke. Very often the complaints are going to be
from the neurobehavioral sequelae. TBI is very weighted on the side of prefrontal cortex function. Memory and attention can also be
affected and the more severe the injury the more global the cognitive deficits. In the milder injury there is more selectivity across
cognitive domains and more equal deficit in severe injury. Behavioral changes can often be devastating. Mood disorders are common,
there’s a lot of vulnerability for depression and mood disregulation. Somatic symptoms and disorders are very critical in this
population. These patients often have chronic pain issues like head ache, back and neck pain. Chronic pain in itself becomes an
overriding factor in itself. All of these things have to be addressed. Seizure disorders are more common than we think in TBI and can
present more as neurobehavioral defects. He brain can be disrupted structurally, chemically, electrically, etc. Most people come in
with more that one impairment.
It can be complicated because a lot of symptoms of PTSD (post traumatic stress disorder) look like TBI. People often refer to
the effects of litigation and malingering in TBI. I have a clinic full of patients who I don’t think are faking but I think are made worse
because they’ve had years of litigation and people looking at them and saying “you’re malingering aren’t you?” So the natural
response of people feeling like they are not being listened to is to embellish and get worse.
Mood disorders generally respond well to treatment, cognitive disorders only do so so. Bottom line is what ever they come in
for you have to assess everything not just their chief complaint. You need to get the full picture to get the appropriate treatment plan
.Depression after TBI is probably underestimated and it is probably due to its presentation. Sometimes the depression results in
difficult behavior, poor ability to respond to rehabilitation, apathetic, non compliant, etc.

Evaluate everything. Neuropsych testing can be invaluable. If someone comes in complaining of neurobehavioral problems
your history should include questions about past TBI. Someone with past injuries may be more likely to show psychiatric type
disturbances. It is important to know that even milder injuries can present with problems unseen so that you can give the right
treatment and not tell the patient they are malingering or something. Lab workup for this is as needed. Imaging is going to be used in a
severe patients based on what you suspect could be wrong.
We use a lot of medications to treat these patients like antidepressants, psycho stimulants, pain medications, epileptic
medications and mood stabilizers. They are not FDA approved for TBI but it is ok to use medications off label as long as you
document it, the proof is in the research. It has been suggested that the Alzheimer’s medications (cholinesterase inhibitors) can be
good for brain disorders that have cognitive problems. Based on the etiology of TBI choosing those drugs makes sense. Two areas are
important. Acute treatments geared toward the secondary injuries. I see acute patients who are more chronic. Even patients years out
from injury can get help. Even if this is not the field you want to go into, knowing when to consult is the key. Rational pharmacology
means we treat patients based on what we think needs to be addressed. For example if we think prefrontal cortex is dysfunctional we
think dopamine. There is also a symptom approach for example if they look depressed or irritable putting them on an SSRI. So it is not
all etiologically driven. Brain injury patients of any cause are more sensitive to side effects and you have to be extremely cautious no
matter what you give them especially those that might effect their mood or cognition. Remember the somatic symptoms; you can’t just
treat one thing you have to treat all symptoms. If they are in pain or not sleeping it worsens everything. Consider a sleep study. This is
a list of different medications we may use with TBI. Each clinician tends to have his/her own library.
Let me just end on an interesting story. Someone did a post mortem assessment of the Red Baron. Turns out he had a very
significant brain injury and part of the reason he went down behind enemy lines may be because he had poor judgment and showed
symptoms of TBI which altered his ability and put him at harm. So being whacked in the head is not good.

Bb1 15 past lecture summaries

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