Lesson 3: The Brain

Several years ago the Brain Injury Association of America announced the development of a blood test that could be used in cases of suspected brain injury. Military researchers used knowledge of the chemicals released by damaged brain cells to develop a non-invasive test that would help diagnose someone with suspected brain injury promptly. This test could be extremely useful for athletes suspected of concussion as well. * Update: https://www.aarp.org/health/brain-health/info-2018/concussion-blood-test-fd.html

In this lesson, the brain will be investigated from many different perspectives. It might seem that brain anatomy is all about memorizing lots of vocabulary. Indeed there are a lot of terms for this lesson. But we’re just as concerned about WHY we understand the function for these brain regions and how these brain regions work TOGETHER to help with functions. In this lesson, you’ll have the opportunity to learn about brain form and function using your first laboratory activity – the dissection of a sheep brain. While we are not examining the response of sheep to drugs () we do learn a lot about brain anatomy using this model organism. With regard to drugs, different drugs will cause different symptoms. Some might make a user euphoric. Others might make a user wakeful. Understanding which brain areas are responsible for pleasure and sleepiness will help you understand how and where these drugs act.

Objectives

to understand regions of the brain, what they are called and what they do to understand the methods used to determine the relationship between brain form

and function to understands elements of how structures are organized into the brain to understand the coordinated functions of connected brain areas (pathways) to understand why we feel rewarded with some activities and choose to repeat them

Before you begin! Pretest See how many you can figure out. This is not turned in!

1. A drug binds to receptors in the hippocampus. We might expect which of the following symptoms in a user of this drug? Circle ALL that are correct based ONLY on this information.

Exhaustion, Forgetfulness, Irritability, Nausea, relief from pain, hallucination

2. What did Phineas Gage tell us about brain organization?

3. Adenosine is a brain chemical that makes feel sleepy and which inhibits the reticular pathway. Based on this, which is true about how caffeine works.

Caffeine is an adenosine agonist that stimulates the reticular pathwayCaffeine is an adenosine agonist that inhibits the reticular pathway Caffeine binds outside the reticular pathway and stimulates adenosine releaseCaffeine is an adenosine antagonist that inhibits the reticular pathway Caffeine is an adenosine antagonist that stimulates the reticular pathway

4. Where is gray matter relative to white matter?Gray matter is found in the cerebellum while white matter is found in the cerebrumGray matter is found on the outside of both cerebrum and cerebellum, white matter is

on the insideWhite and gray matter are sprinkled about randomly in the brain

Guiding Questions

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1. Which brain regions are important for particular functions?2. How do we know about the relationship between brain structure and functions?3. How is the brain organized?4. How do brain regions integrate with others to enable different functions?

 Key Terms Gray matter vs. White matter Cerebrum Cerebellum Brain stem Meninges Thalamus Hypothalamus Hippocampus Corpus Callosum

Amygdala Insula Hemisphere PET and MRI scans Limbic Pathway Reticular Pathway Reward Pathway Nucleus accumbens Ventral tegmental area

Activity One: Learning About the Brain from Brain Damage

In this activity, we’ll ask you to consider HOW we know that a particular brain area is responsible for the function we associate with that region. To study this, we’ll use case studies, each showing how patients with specific symptoms were also found to have specific brain injuries. For each case, please keep in mind this guiding question: how does brain damage help us correlate brain anatomy with brain function. The cases are:

o Phineas Gageo Von Economoo H.M. (Henry Gustav Molaisen)

To learn about these famous people in neuroscience, follow this link to the presentation “Brain Damage”. https://canvas.uw.edu/courses/1014586/pages/activity-3-1-learning-about-the-brain-from-brain-damage?module_item_id=6054381 We will watch this together in class. This may or may not be allowed on your own computers.

You'll learn more these famous people in neuroscience in the following presentation.

Presentation: Brain Damage  by Dr. Linda Martin-Morris (9:12)

Click http://uweoconnect.extn.washington.edu/public_brain_damage/ link to open resource. Again- I’m not sure if these are available to students on the new computers but I will show it during class and have it available during anchor and before school if you miss it.

One more fascinating story of brain damage. Imagine this. Your grandfather has a stroke. He is a nicotine addict and so while in the hospital (he can't smoke in the hospital!) the nurses offer him a nicotine patch.  Your grandfather, who never had any success quitting before, now says, "no thanks, I no longer crave nicotine"! How could this be? Nicotine is one of the hardest drugs to stop using. But in one instant, your grandfather's addiction is cured. 

A number of these cases arose recently and Dr. Naqvi and colleagues published their findings in Science in 2006. The abstract to that article is found here: http://www.sciencemag.org/content/315/5811/531.abstract. Read it if you are interested.

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If you are interested in a 3-D, spinning image of the brain that includes brain parts, functions and fun facts consider downloading the 3-D brain app onto your phone. Its free! http://www.g2conline.org/ As of now, the computer version requires a program that I cannot seem to get on our new school devices.

Activity Two: Mapping Brain Regions by ImagingAnother way to associate brain anatomy and brain function is to use imaging, or brain scans. Two types of neuroimaging are regularly used, and an understanding of each will allow you to better understand how the technique helps us map the brain. The techniques are Positron Emission Tomography or PET scan and Magnetic Resonance Imaging, or MRI analysis. Start by visiting In class we will play the video that shows a methamphetamine user getting a brain scan to look at his brain before and after methamphetamine use. Don’t get bogged down in worrying about what dopamine and the reward pathway are yet.

PET scans are very specific in that they use a particular, radioactively labeled molecule and examine where that molecule localizes in the brain. Frequently, the molecule examined is glucose. Glucose utilization helps us know which areas of the brain are most active (active cells metabolize glucose efficiently). The PET scan shown (source nida.nih.gov) of two brains, one the brain of a cocaine user shows the difference seen in a brain exposed to cocaine. Red in this scan indicates areas of intense glucose utilization. Examine the photos and express both what you see in terms of differences between the control and the cocaine brain as well as what you can interpret from what you see. Image citation – nida.nih.gov

Test of content

In the PET scan, I see:

This observation means that:

MRI scans are specific for a very different reason. Rather than using radioactively labeled tracer molecules, the MRI relies on the fact that different tissue types in different states of activity will respond differently to a magnetic field. The magnets are used to alter the alignment of subatomic particles. When the magnet is switched off, the electrons return to their normal state at different rates. Thus some tissues will remain aligned while others do not. Alignment will vary based on cell types in the region as well as cell activity. In the MRI shown (source http://drugabuse.com) subjects who were cocaine abusers have been scanned when they are exposed to neutral stimuli, unrelated to drug use (on the left) or drug-related cues, such as images of someone smoking a crack-pipe. The scan highlights in white areas that are active in response to these cures. Drug related cues elicits more activity in some brain areas and less in others. These studies are being used to better understand relapse – why addicts are still very tempted to resume drug use.

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Activity Three: Brain Dissection Study the areas of the brain shown in Figures 1 and 2 at this

site: http://teens.drugabuse.gov/mom/tg_brain.php For more detailed illustrations:

Study the brain images at the following. In particular, click on cerebellum, corpus callosum, thalamus, and hypothalamus.http://www.mhhe.com/socscience/intro/inpsych/sylvius_brain/sylvius.swf

Review the interactive Human Brain Map athttp://www.bbc.co.uk/science/humanbody/body/interactives/organs/brainmap/, by clicking on "Structure" and then cerebrum, brain stem, and cerebellum. After clicking on limbic system, you can locate corpus callosum, hypothalamus, and thalamus.

Review the description of meninges at http://faculty.washington.edu/chudler/cover.html. Obtain the laboratory manual write up (Big Beautiful Brains) for the brain dissection (sheep) as well as the

tools and tissue needed to dissect a sheep's brain. Most laboratory activities require 1–1.5 hours to complete. So ensure that you have the time available to devote to this activity before beginning! At the end of the activity, you will be required to complete a lab homework assignment (Brain Lab Homework).

Test of content

What do you notice about the relative positions of gray and white matter in the brain?

Use the diagram given to apply labels to the human brain. In addition to labeling brain regions, apply descriptions to these labels for the function of these brain areas. You should be able to label the cerebrum, cerebellum, brain stem, corpus callosum, thalamus, hypothalamus, and meninges. Image copyright protected – Audesirk and Audesirk – any unlabeled midline will do.

Cerebrum – enabling rational thought, decision making, impulse control, perceptionCerebellum – enabling balance and coordinationBrain stem – connecting the brain to the spinal cord and controlling rate of breathingCorpus callosum – connecting the left and right hemispheresThalamus – relaying sensory information to the right area of the cerebrum depending upon the senseHypothalamus – homeostasis – keeping body temperature and hunger, for instance, balancedMeninges – protecting the brain, providing a fluid-filled enclosure

Activity Four: Brain Organization

Early in the 20th century, it was thought that the brain was so complex, and thus we would never understand how it was organized. While it is true that the brain is complex, there are still many features of that organization that we do understand. To consider the human brain and its organization, start by viewing a presentation in class. The brains used were provided by the University of Washington Hospital from patients’ families – patients who died from illness or injury that was not related to brain dysfunction.

TEST OF CONTENT

In what ways were the human brain and sheep brain similar? Select ALL answers that are correct.

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Both are roughly the same sizeBoth have large olfactory bulbsBoth have cerebellum positioned right above the brain stemBoth are wrinkly, although the human brain is more wrinklyBoth organize their cerebrum into left and right hemispheres

Activity Five: Brain Pathways – Introduction and Learning Pathway

While it might be tempting to think about particular brain areas, for instance, the hypothalamus, and imagine that homeostasis relies only on that region. However, brain regions are connected to each other and typically the entire network of interconnected regions is responsible for the function under investigation.

Consider first how we learn. The “learning pathway” is a connected network of brain cells that starts with cells in sensory organs (ears and eyes for instance) which acquire information. They transmit that information from sensory organ to thalamus. The thalamus determines where the information needs to go in order to perceive that information (see below) and also sends this information to the hippocampus (image citation georg@ucsb.edu) . In the hippocampus, the momentary awareness of the sensory input is translated into memory. The hippocampus corresponds about that memory with the cerebral cortex, primarily the frontal cortex. Thus learning involves sensory organ thalamus hippocampus frontal cortex.

Recall patient H.M.? (I hope you remember him – if not – consider what brain area might be functioning poorly ). The brain area his neurosurgeon damaged in an attempt to cure his epilepsy was the hippocampus.

Activity Six: Brain Pathways – Sensing Pathway

In order to know about the world around us, our sensory organs (for instance eyes and ears) are not enough. There are many blind people who have eyes that work just fine. But information from the eyes needs to arrive at and be interpreted by the brain. Information flow in the sensory pathway depends upon sensory organ. The following pathway corresponds to all senses with the exception of the nose. Sensory organ thalamus appropriate portion of the cerebral cortex. What is the appropriate portion of the cerebral cortex? Recall that the thalamus’ job is to

relay information depending upon origin. Visual information arrives in the cerebrum in an area just above the cerebellum. Auditory information completes its journey in the Wernicke’s area (image citation http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=neurosci&part=A1891 ) .

Perhaps the most striking example of brain organization comes from the somatosensory cortex. Our sense of touch is

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perceived by a brain region located above the ears called the somatosensory cortex. This image of a portion of the somatosensory cortex in human and sheep color codes the portions of the brain which are responsible for detecting touch by each of the five digits on the hand. This color code corresponds to the colors of the digits which are transmitting sensory information.

TEST OF CONTENT Cross two of your fingers so that you can put some thin object between them. For

instance, if you cross your index and middle fingers, the object will be touching the thumb-side of the index finger and the ring-finger side of the middle finger. Close your eyes so you can focus on this experiment. How many objects do you think you detect? Explain this in terms of the somatosensory cortex.

Activity Seven: Brain Pathways – Limbic Pathway

The story of Phineas Gage helps us understand the importance of the limbic pathway in regulating emotion. Destruction of the frontal lobe and connected areas of the brain took a mild-mannered and proud employee and tenant and turned him into an angry and profane individual. (Image citation – Audesirk and Audesirk – copyright protected)The limbic pathway includes the hippocampus, the hypothalamus, and the amygdala, all of which integrate the story to be told to the frontal lobe. Thus these structures coordinate information and give the complete analysis to the frontal lobes for appropriate response. Keep in mind, we tend to want these pathways to move in one direction only. But this is not the case. Information goes from the limbic system to the frontal cortex, informing us on how we feel and subsequently will behave depending on the circumstances. But the frontal cortex also feeds back to the limbic system. This feedback will help to reinforce the emotional learning we are participating in and in the case of drug use, reinforces drug-seeking behaviors.

TEST OF CONTENT The sense of smell bypasses the thalamus. In fact, networks from nose to brain are

contained within the limbic system. Walk into a house in which you smell bread baking and you often feel a strong sense of comfort and “home coming”. People report feeling calm and happy when they smell freshly baked products. How does this observation help you integrate what you learned about learning, sensing, and limbic pathways? We have an emotional response to smells because the circuitry of smell perception is integrated with the circuitry of emotion.

Activity Eight: Brain Pathways – Reticular Pathway

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The reticular pathway allows us to feel sleepy or wakeful. Reticular pathway information comes from our senses through the brain stem and arrives at the thalamus (as with sensory information). But upon arrival, in addition to determining how we perceive these incoming stimuli, the thalamus-to-cerebrum connection also determines how we respond to them. If we’re sound asleep, some sound will rouse us and others will not. The reticular pathway serves the purpose of enabling sleep when we are in need of sleep. It helps us feel sleepy and helps us keep our sleep from being interrupted if we have not satisfied our sleep quotient. The reticular system uses electrical inputs from the thalaums and chemical inputs in the form of adenosine (a brain chemical whose concentration is directly correlated with the need for sleep). If we have a lot of adenosine, not only will we feel sleepy, but inputs from the thalamus will be easier to ignore. (image citation – benbest.com – we could hand draw just as well)

TEST OF CONTENT * just for practice. Likely to be on a real test.Which person helped us learn more about the anatomy involved in differentiating

between wakefulness and sleepiness?Phineas GageVon EconomoPatient H.M.

Activity Nine: Brain Pathways – Reward Pathway

Our final pathway is the one we visited earlier in the video clip pertaining to brain scans. Recall that the methamphetamine user showed changes in a brain region when using methamphetamine. These changes were present in a region of the midbrain near to the limbic pathway.

Our brains have can prepare us for survival both for ourselves and for our species. We therefore have a pleasure center that is stimulated when we engage in activities that promote our survival like eating and promote the survival of humans generally (like mating). This pleasure center can also be stimulated by activities that do not relate to survival like gambling and video games. It is likely that these activities are addictive for some in part BECAUSE they stimulate our pleasure center, our reward pathway.

We understood that this region of the brain was involved in pleasure as far back as 1950. Electrical stimulation of the reward pathway was tested 50 years ago as a mechanism of treating depression. Depressed patients testified that they felt “sexy” and giggled foolishly when their reward system was stimulated. Additionally, when allowed to administer the electrical stimulation on their own, they continued to stimulate the nucleus accumbens without interruption.

Similarly, mice will go to great lengths to stimulate their reward pathway. By training mice that the press of a lever will result in stimulation of the reward pathway, it was observed that mice would press the lever to obsession. Some have been observed to press the lever without bothering to stop for food or water. Move the needle that administers stimulation just a bit to one side and the mouse will stop pressing the lever.

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The site of stimulation that caused people and rodents to self-stimulate repeatedly is called the nucleus accumbens (NA). The reward pathway centers on the NA. Inputs regulate the release of a neurochemical called dopamine in the NA. Release of dopamine here sends a message to the frontal cortex that you have engaged in something highly pleasurable (and important for your survival). Drugs that cause an increase in dopamine release here also reward you with pleasure and stimulate your desire to repeat that experience. These drugs may work directly on the NA, or on a brain region nearby that regulates the NA. This area, the ventral tegmental area (VTA), communicates to the NA which communicates to the frontal cortex. But the frontal cortex also feeds back, reinforcing drug seeking behaviors.

TEST OF CONTENTNicotine binds to receptors in the ventral tegmental area. Nicotine also results in

dopamine release and pleasure. Which of these statements describes how nicotine is related to dopamine?

Nicotine turns off VTA neurons that turn on dopamine releaseNicotine turns on VTA neurons that turn on dopamine releaseNicotine turns on NA neurons that stimulate dopamine release in the frontal

cortexNicotine turns off NA neurons which inhibits dopamine release in the frontal

cortexNicotine promotes prefrontal cortex function, bypassing the reward pathway.

Some people have “reward deficiency syndrome”. If dopamine is the reward chemical, which of these scenarios might explain a person who has reward deficiency syndrome?

Their dopamine receptors are very sensitive to dopamineTheir dopamine gets metabolized abnormally slowlyTheir dopamine receptors poorly bind to dopamineThey make an excess amount of dopamine

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