Friday, September 30, 2011

MIT OPEN COURSEWARE: A Clinical Approach to the Human Brain


A Clinical Approach to the Human Brain

As taught in: Fall 2006

Image of the brain with key areas highlighted.
Activity in the highlighted areas in the prefrontal cortex may affect the level of dopamine in the mid-brain, in a finding that has implications for schizophrenia. (Image courtesy of the National Institutes of Mental Health.)

Instructors:

Prof. Thomas Byrne

MIT Course Number:

9.22J / HST.422J

Level:

Undergraduate
 

Course Description

This course is designed to provide an understanding of how the human brain works in health and disease, and is intended for both the Brain and Cognitive Sciences major and the non-Brain and Cognitive Sciences major. Knowledge of how the human brain works is important for all citizens, and the lessons to be learned have enormous implications for public policy makers and educators.
The course will cover the regional anatomy of the brain and provide an introduction to the cellular function of neurons, synapses and neurotransmitters. Commonly used drugs that alter brain function can be understood through a knowledge of neurotransmitters. Along similar lines, common diseases that illustrate normal brain function will be discussed. Experimental animal studies that reveal how the brain works will be reviewed.
Throughout the seminar we will discuss clinical cases from Dr. Byrne's experience that illustrate brain function; in addition, articles from the scientific literature will be discussed in each class.

Syllabus

Course Meeting Times

Lectures: 2 sessions / week, 1.5 hours / session

Goals and Overview of Course

Taught by a neurologist, the course is designed to provide an understanding of how the human brain works in health and disease, and is intended for both the Brain and Cognitive Sciences major and the non-Brain and Cognitive Sciences major. Knowledge of how the human brain works is important for all citizens, and the lessons to be learned have enormous implications for public policy makers and educators.
Many new technologies allow us to map brain function. For example, functional magnetic resonance imaging (fMRI) shows brain regions that are active when we see, move a finger, read, experience emotion or perform mental arithmetic. The course will explore how fMRI reveals that visual and spatial information, such as pictures, are stored on the right side of the brain and words are stored on the left. We will study how fMRI is being used in dyslexia and other brain disorders to assess organization of the brain in disease and its reorganization following treatment.
During "critical periods" in development, appropriate activity is required for the acquisition of mature brain circuitry and function. For example, a child born with a "lazy," or strabismic, eye must be forced to use that eye, either by surgical correction of the eye position or by patching the good eye, before about 8 years of age or the strabismic eye will never develop normal vision. Along similar lines, to speak a language with a native accent, the language must be learned before puberty. These examples of how the brain "wires" itself during critical periods of "activity-dependent" development will be discussed as outlined in the syllabus.
Of course, beyond childhood we can still learn new information and skills. The course will review imaging studies that reveal how the organization of the brain is modified by training and rehearsal. For example, we will discuss experiments showing that the area of brain that controls finger movements and sensations is reorganized in musicians who rehearse intensively. Interestingly, even mental rehearsing of keyboard instruments can lead to the reorganization of brain circuits in the premotor area of the brain, which is the site where planning of motor activities are maintained. Such mental rehearsing is routinely done by musicians (and athletes alike) because it can give rise to an improvement in performance.
The course will cover the regional anatomy of the brain and provide an introduction to the cellular function of neurons, synapses and neurotransmitters. Commonly used drugs that alter brain function can be understood through a knowledge of neurotransmitters. Along similar lines, common diseases that illustrate normal brain function will be discussed. Experimental animal studies that reveal how the brain works will be reviewed.
The primary text for the course will be Neuroscience, edited by Dale Purves, et al. Throughout the seminar we will discuss clinical cases from Dr. Byrne's experience that illustrate brain function; in addition, articles from the scientific literature will be discussed in each class.

Course Requirements

Each student is required to present at least one paper to the class. The papers will be selected from the asterisked articles in the lectures.

Grading

ACTIVITIESPERCENTAGES
Two Exams60%
Final Exam30%
Class Participation10%

The class participation portion will be derived as follows: half (5% of final grade) will be determined by the presentation and half (5% of final grade) will be determined by participation in class discussions throughout the term.
 
 

Calendar

SES #TOPICS
1Brain Anatomy and Imaging
2Cells and Brain Imaging
3Synaptic Potentials
4fMRI of the Human Brain
Prof. John Gabrieli, MIT
5Seeing and Reading Others
6Cognitive Enhancement through Neuropharmacology
7Oxytocin and Trust, Antidepressants and Neurogenesis
8Neurogenesis: Teaching Old Dogs New Tricks
9Test 1
10Critical Periods: Implications for Education
11Neuroplasticity in the Adult
12Language, Dyslexia and Universal Grammar
13Visual System I
14Visual Neglect and Prosopagnosia
15Rembrandt, Leonardo, Monet: How We See Them
16Sensory System and Pain
17Placebo, Empathy, and Theory of Mind
18Test 2
19Emotions and Feelings: Romantic and Maternal Love
20Neuroscience and Marketing: Hitting the "Sweet Spot"
21Learning and Memory: The Case of HM
22Structure and Function of Brains with Superior Memory
23How Emotion and Antidepressants Affect Memory
24Depression, Anxiety and Psychosis
25Vision, Memory and Feelings: Binding them Together
26Music, Math and the Brain
Additional Topic: Consciousness / Neuroeconomics
Additional Topic: Can Thinking Prevent Dementia?
 
 

Readings

Primary Text

Amazon logo Purves, Dale, et al. Neuroscience. Sunderland, MA: Sinauer Associates, 2004. ISBN: 9780878937257.

Articles

Reading of the abstracts is often sufficient to gain a general understanding of the results and significance of the article. The introduction of the articles usually provide helpful background information which makes the article more understandable. The figures in many of the articles will be discussed when they show functional brain imaging. Since the articles often have technical information which requires specialized knowledge and experience we will not be routinely reading articles cited in the syllabus in their entirety. We will discuss those parts of the article which should be read to prepare for class discussion.

Optional Texts

Amazon logo Kandell, Eric, James Schwartz, and Thomas Jessell. Principles of Neural Science. New York, NY: McGraw-Hill, 2000. ISBN: 9780878937257.
Amazon logo Livingstone, Margaret. Vision and Art: The Biology of Seeing. New York, NY: Abrams, 2002. ISBN: 9780810904064.
Amazon logo Matthews, Paul, and Jeffrey McQuain. The Bard on the Brain: Understanding the Mind through the Art of Shakespeare and the Science of Brain Imaging. New York, NY: Dana Press, 2003. ISBN: 9780972383028.
Amazon logo Zeki, Semir. Inner Vision: An Exploration of Art and the Brain. New York, NY: Oxford University Press, 2000. ISBN: 9780198505198.
Amazon logo Sacks, Oliver. The Man Who Mistook His Wife for a Hat: And Other Clinical Tales. New York, NY: Simon and Schuster, 1998. ISBN: 9780198505198.
Amazon logo Zeman, Adam. Consciousness: A User's Guide. New Haven, CT: Yale University Press, 2004. ISBN: 9780300104974.
Amazon logo Damasio, Antonio. Looking for Spinoza: Joy, Sorrow, and the Feeling Brain. Orlando, FL: Harcourt Brace, 2003. ISBN: 9780156028714.
SES #TOPICSREADINGS
1Brain Anatomy and Imaging

Required Reading

Purves, Dale, et al. Neuroscience. pp. 1-28.
2Cells and Brain Imaging

Required Reading

Purves, Dale, et al. Neuroscience. pp. 1-12, 31-46, and 63-67.
3Synaptic Potentials

Required Reading

Purves, Dale, et al. Neuroscience. pp. 1-12, 31-46, 63-67, 96-127, and 129-147.

Optional Reading

Sacks, Oliver. "The Disembodied Lady," "The Man Who Fell Out of Bed," "Hands," "Phantoms," "On the Level," and "Eyes Right!" In The Man Who Mistook His Wife for a Hat. pp. 43-79.
4fMRI of the Human Brain
Professor John Gabrieli, MIT

Required Reading

Brewer, James B., Zuo Zhao, John E. Desmond, Gary H. Glover, and John D. E. Gabrieli. "Making Memories: Brain Activity that Predicts How Well Visual Experience Will Be Remembered." Science 281, no. 5380 (1998): 1185-1187.
Turhan, Canli, Zuo Zhao, James Brewer, John D. E. Gabrieli, and Larry Cahill. "Event-related Activation in the Human Amygdala Associates with Later Memory for Individual Emotional Experience." Journal of Neuroscience 20 (2000): 1-5.
Turhan, Canli, Heidi Sivers, Susan L. Whitfield, Ian H. Gotlib, and John D. E. Gabrieli. "Amygdala Response to Happy Faces as a Function of Extraversion." Science 296, no. 5576 (2002): 2191.

Optional Reading

DeCharms, R. Christopher, Fumiko Maeda, Gary H. Glover, David Ludlow, John M. Pauly, Deepak Soneji, John D. E. Gabrieli, and Sean C. Mackey. "Control over Brain Activation and Pain Learned by Using Real-time Functional MRI." Proceedings of the National Academy of Sciences 102, no. 5 (2005): 18626-18631.
Poldrack, Russell A., John E. Desmond, Gary H. Glover, and John D. E. Gabrieli. "The Neural Basis of Visual Skill Learning: An FMRI Study of Mirror Reading." Cerebral Cortex 8 (1998): 1-10.
Heeger, David J., and David Ress. "What Does FMRI Tell Us about Neuronal Activity?" Nature Reviews Neuroscience 3 (2002): 142-141.
5Seeing and Reading Others

Required Reading

Adolphs, Ralph. "Neural Systems for Recognizing Emotion." Current Opinion in Neurobiology 12, no. 2 (2002): 169-177.
Sanfey, Alan G., James K. Rilling, Jessica A. Aronson, Leigh E. Nystrom, and Jonathan D. Cohen. "The Neural Basis of Economic Decision-making in the Ultimatum Game." Science 300, no. 5626 (2003): 1765-1758.
Adolphs, Ralph, Hanna Damasio, Daniel Tranel, Greg Cooper, and Antonio R. Damasio. "A Role for Somatosensory Cortices in the Visual Recognition of Emotion as Revealed by Three-dimensional Lesion Mapping." Journal of Neuroscience 20, no. 7 (2000): 2683-2690.
Iacoboni, Marco, Roger P. Woods, Marcel Brass, Harold Bekkering, John C. Mazziotta, and Giacomo Rizzolatti. "Cortical Mechanisms of Human Imitation." Science 286, no. 5449 (1999): 2526-2528.

Optional Reading

Camerer, Colin F. "Psychology and Economics: Strategizing in the Brain." Science 300, no. 5626 (2003): 1673-1675.
Gallese, Vittorio, and Alvin Goldman. "Mirror Neurons and the Simulation Theory of Mind-reading." Trends in Cognitive Science 2, no. 12 (1998): 493-501.
6Cognitive Enhancement through Neuropharmacology

Required Reading

Knecht, Stefan, Caterina Breitenstein, Stefan Bushuven, Stefanie Wailke, Sandra Kamping, Agnes Floel, Pienie Zwitserlood, and E. Bernd Ringelstein. "Levodopa: Faster and Better Word Learning in Normal Humans." Annals of Neurology 56, no. 1 (2004): 20-26.
Butefisch, Cathrin M., Benjamin C. Davis, Lurny Sawaki, Daniel Waldvogel, Joseph Classen, Leonid Kopylev, and Leonardo G. Cohen. "Modulation of Use-dependent Plasticity by D-amphetamine." Annals of Neurology 51, no. 1 (2001): 59-68.
Hall, Stephen S. "The Quest for a Smart Pill." Scientific American 289, no. 33 (2003): 36-45.
Caplan, Arthur. "Is Better Best?" Scientific American 289, no. 33 (2003): 104.
Yesavage, J. A., M. S. Mumenthaler, J. L. Taylor, L. Friedman, R. O'Hara, J. Sheikh, J. Tinklenberg, and P. J. Whitehouse. "Donepezil and Flight Simulator Performance: Effects on Retention of Complex Skills." Neurology 59 (2002): 125.

Optional Reading

Gron, Georg, Matthias Kirstein, Axel Thielscher, Matthias W. Riepe, and Manfred Spitzer. "Cholinergic Enhancement of Episodic Memory in Healthy Young Adults." Psychopharmacology 182, no. 1 (2005): 170-179.
Santarelli, Luca, et al. "Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants." Science 301, no. 5634 (2003): 805-809.
D'Sa, Carrol, and Ronald S. Duman. "Antidepressants and Neuroplasticity." Bipolar Disorders 4, no. 3 (2002): 183-194.
Floel, Agnes, et al. "Dopaminergic Influences on Formation of a Motor Memory." Annals of Neurology 58, no. 1 (2005): 121-130.
7Oxytocin and Trust, Antidepressants and Neurogenesis

Required Reading

Damasio, Antonio. "Human Behaviour: Brain Trust." Nature 435 (2005): 571-572.
Kosfeld, Michael, Markus Heinrichs, Paul J. Zak, Urs Fischbacher, and Ernst Fehr. "Oxytocin Increases Trust in Humans." Nature 435 (2005): 673-676.
Harmer, Catherine J., Nicholas C. Shelley, Philip J. Cowen, and Guy M. Goodwin. "Increased Positive versus Negative Affective Perception and Memory in Healthy Volunteers Following Selective Serotonin and Norepinephrine Reuptake Inhibition." American Journal of Psychiatry 161 (2004): 1256-1263.
Santarelli, Luca, et al. "Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants." Science 301, no. 5634 (2003): 805-809.
Vogel, Gretchen. "Depression Drugs' Powers May Rest on New Neurons." Science 301, no. 5634 (2003): 757.
Eriksson, Peter S., et al. "Neurogenesis in the Adult Human Hippocampus." Nature Medicine 4 (1998): 1313-1317.
Wilson, Robert S., et al. "Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease." Journal of the American Medical Association 287, no. 6 (2002): 742-748.
Ball, Karlene, et al. "Effects of Cognitive Training Interventions with Older Adults: A Randomized Controlled Trial." Journal of the American Medical Association 288, no. 18 (2002): 2271-2281.

Optional Reading

Miller, Greg. "Economic Game Shows How the Brain Builds Trust." Science 308, no. 5718 (2005): 36.
King-Casas, Brooks, et al. "Getting to Know You: Reputation and Trust in a Two-person Economic Exchange." Science 308, no. 5718 (2005): 78-83.
8Neurogenesis: Teaching Old Dogs New Tricks

Required Reading

Shors, Tracey J., et al. "Neurogenesis in the Adult Is Involved in the Formation of Trace Memories." Nature 410 (2001): 372-376.
Drapeau, Elodie, et al. "Spatial Memory Performances of Aged Rats in the Water Maze Predict Levels of Hippocampal Neurogenesis." Proceedings of the National Academy of Sciences 100, no. 24 (2003): 14385-14390.
Gould, Elizabeth, Anna Beylin, Patima Tanapat, Alison Reeves, and Tracey J. Shors. "Learning Enhances Adult Neurogenesis in the Hippocampal Formation." Nature Neuroscience 2 (1999): 260-265.
Verghese, Joe, et al. "Leisure Activities and the Risk of Dementia in the Elderly." New England Journal of Medicine 348, no. 25 (2003): 2508-2516.

Optional Reading

Kempermann, Gerd, and Fred H. Gage. "New Nerve Cells for the Adult Brain." Scientific American 280, no. 5 (1999): 48-53.
Gage, Fred H. "Brain, Repair Yourself." Scientific American 289, no. 3 (2003): 47-54.
Coyle, Joseph T. "Use It or Lose It - Do Effortful Mental Activities Protect against Dementia?" New England Journal of Medicine 348, no. 25 (2003): 2489-2490.
Van Praag, Henriette, Gerd Kempermann, and Fred H. Gage. "Running Increases Cell Proliferation and Neurogenesis in the Adult Mouse Dentate Gyrus." Nature Neuroscience 2 (1999): 266-270.
Van Praag, Henriette, Brian R. Christie, Terrence J. Sejnowski, and Fred H. Gage. "Running Enhances Neurogenesis, Learning, and Long-term Potentiation in Mice." Proceedings of the National Academy of Sciences 96, no. 23 (1999): 13427-13431.
Greenough, William T., Neal J. Cohen, and Janice M. Juraska. "New Neurons in Old Brains: Learning to Survive?" Nature Neuroscience 2 (1999): 203-205.
D'Sa, Carrol and Ronald S. Duman. "Antidepressants and Neuroplasticity." Bipolar Disorders 4, no. 3 (2002): 183-194.
Vogel, Gretchen. "Depression Drugs' Powers May Rest on New Neurons." Science 301, no. 5634 (2003): 757.
9Test 1 
10Critical Periods: Implications for Education

Required Reading

Purves, Dale, et al. Neuroscience. pp. 557-574.
Kim, Karl H. S., Norman R. Relkin, Kyoung-Min Lee, and Joy Hirsch. "Distinct Cortical Areas Associated with Native and Second Languages." Nature 388 (1997): 171-174.
Christakis, Dimitri A., Frederick J. Zimmerman, David L. DiGiuseppe, and Carolyn A. McCarty. "Early Television Exposure and Subsequent Attentional Problems in Children." Pediatrics 113 (2004): 708-713.

Optional Reading

Penn, Anna A., and Carla J. Shatz. "Brain Waves and Brain Wiring: The Role of Endogenous and Sensory-driven Neural Activity in Development." Pediatric Research 45, no. 4 (1999): 447-458.
Buffelli, Mario, et al. "Genetic Evidence that Relative Synaptic Efficacy Biases the Outcome of Synaptic Competition." Nature 424 (2003): 430-434.
Thompson, Paul M., et al. "Genetic Influences on Brain Structure." Nature Neuroscience 4, no. 12 (2001): 1-6.
Amazon logo Curtiss, Susan. Genie: A Psycholinguistic Study of a Modern-day "Wild Child". New York, NY: Academic Press, 1977. ISBN: 9780121963507.
Kuhl, Patricia K., Karen A. Williams, Francisco Lacerda, Kenneth N. Stevens, and Bjorn Lindblom. "Linguistic Experience Alters Phonetic Perception in Infants by Six Months of Age." Science 255, no. 5044 (1992): 606-608.
Gogtay, Nitin, et al. "Dynamic Mapping of Human Cortical Development during Childhood through Early Adulthood." Proceedings of the National Academy of Sciences 101, no. 21 (2004): 8174-8179.
11Neuroplasticity in the Adult

Required Reading

Purves, Dale, et al. Neuroscience. pp. 402-12, 599-602.
Gaser, Christian, and Gottfriend Schlaug. "Gray Matter Differences between Musicians and Nonmusicians." Annals of the New York Academy of Sciences 999 (2003): 514-517.
Elbert, Thomas, Christo Pantev, Christian Wienbruch, Brigitte Rockstroh, and Edward Taub. "Increased Cortical Representation of the Fingers of the Left Hand in String Players." Science 270, no. 5234 (1995): 305-307.
Holloway, Marguerite. "The Mutable Brain." Scientific American 289, no. 3 (2003): 78-84.
Ball, Karlene. "Effects of Cognitive Training Interventions with Older Adults: A Randomized Controlled Trial." Journal of the American Medical Association 288, no. 18 (2002): 2271-2281.

Optional Reading

Wilson, Robert S., et al. "Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease." Journal of the American Medical Association 287, no. 6 (2002): 742-748.
Verghese, Joe, et al. "Leisure Activities and the Risk of Dementia in the Elderly." New England Journal of Medicine 348, no. 25 (2003): 2508-2516.
Coyle, Joseph T. "Use It or Lose It - Do Effortful Mental Activities Protect against Dementia?" New England Journal of Medicine 348, no. 25 (2003): 2489-2490.
D'Sa, Carrol, and Ronald S. Duman. "Antidepressants and Neuroplasticity." Bipolar Disorders 4, no. 3 (2002): 183-194.
12Language, Dyslexia and Universal GrammarRequired Reading
Purves, Dale, et al. Neuroscience. pp. 637-657.
Simos, P. G., et al. "Dyslexia-specific Brain Activation Profile Becomes Normal Following Successful Remedial Training." Neurology 58 (2002): 1203-1213.
Shaywitz, Sally E., and Bennett A. Shaywitz. "Dyslexia (Specific Reading Disability)." Pediatrics in Review 24 (2003): 147-153.

Optional Reading

Simos, Panagiotis G., et al. "Brain Activation Profiles during the Early Stages of Reading Acquisition." Journal of Child Neurology 17, no. 3 (2002): 159-163.
Sacks, Oliver. "The President's Speech." In The Man Who Mistook His Wife for a Hat. pp. 80-84.
Musso, Mariacristina, et al. "Broca's Area and the Language Instinct." Nature Neuroscience 6 (2003): 774-781.
Marcus, Gary F., Athena Vouloumanos, and Ivan A. Sag. "Does Broca's Play by the Rules?" Nature Neuroscience 6 (2003): 651-652.
13Visual System I

Required Reading

Purves, Dale, et al. Neuroscience. pp. 259-263, 278-281, and 619-623.
Phelps, Elizabeth A., et al. "Activation of the Left Amygdala to a Cognitive Representation of Fear." Nature Neuroscience 4 (2001): 437-441.
Phillips, M. L., et al. "A Specific Neural Substrate for Perceiving Facial Expressions of Disgust." Nature 389 (1997): 495-498.

Optional Reading

Sacks, Oliver. "Visions of Hildegard," and "The Man Who Mistook His Wife for a Hat." In The Man Who Mistook His Wife for a Hat. pp. 166-70, 8-22.
14Visual Neglect and Prosopagnosia

Required Reading

Purves, Dale, et al. Neuroscience. pp. 259-263, 278-281, and 619-623.
Barton, Jason J. S., Daniel Z. Press, Julian P. Keenan, and Margaret O'Connor. "Lesions of the Fusiform Face Area Impair Perception of Facial Configuration in Prosopagnosia." Neurology 58 (2002): 71-78.
Bisiach, Edoardo, and Claudio Luzzatti. "Unilateral Neglect of Representational Space." Cortex 14 (1978): 129-133.
A fascinating study of patients from Milan with injury to the right parietal lobe reveals that such patients are not aware of the left visual world. (It is illustrated and discussed in Kandel, Schwartz, Jessell, eds. Principles of Neural Science. pp. 398-9.)

Optional Reading

Husain, Masud, and Chris Rorden. "Non-spatially Lateralized Mechanisms in Hemispatial Neglect." Nature Reviews Neuroscience 4 (2003): 26-36.
Fink, G. R., et al. "Where in the Brain Does Visual Attention Select the Forest and the Trees?" Nature 382 (1996): 626-628.
15Rembrandt, Leonardo, Monet: How We See Them

Required Reading

Bisiach, Edoardo, and Claudio Luzzatti. "Unilateral Neglect of Representational Space." Cortex 14 (1978): 129-133.
Wicker, Bruno, et al. "Both of Us Disgusted in My Insula: The Common Neural Basis of Seeing and Feeling Disgust." Neuron 40, no. 3 (2003): 655-664.

Optional Reading

Sacks, Oliver. "The Disembodied Lady," "The Man Who Fell Out of Bed," "Hands," "Phantoms," "On the Level," and "Eyes Right." In The Man Who Mistook His Wife for a Hat. pp. 43-79
Livingstone, Margaret. Vision and Art: The Biology of Seeing.
Zeki, Semir. Inner Vision.
16Sensory System and Pain

Required Reading

Purves, Dale, et al. Neuroscience. pp. 209-227.
Rainville, Pierre, Gary H. Duncan, Donald D. Price, Benoit Carrier, and M. Catherine Bushnell. "Pain Affect Encoded in Human Anterior Cingulate but Not Somatosensory Cortex." Science 277, no. 5328 (1997): 968-971.
Ploghaus, Alexander, et al. "Dissociating Pain from Its Anticipation in the Human Brain." Science 284, no. 5422 (1999): 1979-1981.

Optional Reading

Mogilner, Alon, et al. "Somatosensory Cortical Plasticity in Adult Humans Revealed by Magnetoencephalography." Proceedings of the National Academy of Sciences 90 (1993): 3593-3597.
Ramachandran, V. S. "Behavioral and Magnetoencephalographic Correlates of Plasticity in the Adult Human Brain." Proceedings of the National Academy of Sciences 90 (1993): 10413-10420.
Fink, G. R., et al. "Where in the Brain Does Visual Attention Select the Forest and the Trees?" Nature 382 (1996): 626-628.
Husain, Masud, and Chris Rorden. "Non-spatially Lateralized Mechanisms in Hemispatial Neglect." Nature Reviews Neuroscience 4 (2003): 26-36.
17Placebo, Empathy, and Theory of Mind

Required Reading

Holden, Constance. "Imaging Studies Show How Brain Thinks about Pain." Science 303, no. 5661 (2004): 1121.
Wager, Tor D., et al. "Placebo-induced Changes in FMRI in the Anticipation and Experience of Pain." Science 303, no. 5661 (2004): 1162-1167.
Singer, Tania, et al. "Empathy for Pain Involves the Affective but Not Sensory Components of Pain." Science 303, no. 5661 (2004): 1157-1162.
Kosfeld, Michael, Markus Heinrichs, Paul J. Zak, Urs Fischbacher, and Ernst Fehr. "Oxytocin Increases Trust in Humans." Nature 435 (2005): 673-676.
Optional Reading
Zubieta, Jon-Kar, et al. "Placebo Effects Mediated by Endogenous Opioid Activity on Mu-opioid Receptors." Journal of Neuroscience 25, no. 34 (2005): 7754-7762.
Saxe, R., S. Carey, and N. Kanwisher. "Understanding Other Minds: Linking Developmental Psychology and Functional Neuroimaging." Annual Review of Psychology 55 (2004): 87-124.
Carr, Laurie, Marco Iacoboni, Marie-Charlotte Dubeau, John C. Mazziotta, and Gian Luigi Lenzi. "Neural Mechanisms of Empathy in Humans: A Relay from Neural Systems for Imitation to Limbic Areas." Proceedings of the National Academy of Sciences 100, no. 9 (2003): 5497-5502.
Purves, Dale, et al. Neuroscience, pp. 388-391.
18Test 2 
19Emotions and Feelings: Romantic and Maternal Love

Required Reading

Purves, Dale, et al. Neuroscience, pp. 687-710.
Bartels, Andreas, and Semir Zeki. "The Neural Basis of Romantic Love." NeuroReport 11, no. 17 (2000): 3829-3834.
Nitschke, Jack B., et al. "Orbitofrontal Cortex Tracks Positive Mood in Mothers Viewing Pictures of Their Newborn Infants." NeuroImage 21, no. 2 (2004): 583-592.
Dolan, R. J. "Emotion, Cognition, and Behavior." Science 298, no. 5596 (2002): 1191-1194.

Optional Reading

Bartels, Andreas, and Semir Zeki. "The Neural Correlates of Maternal and Romantic Love." NeuroImage 21, no. 3 (2004): 1155-1166.
Amazon logo Damasio, Antonio. Looking for Spinoza: Joy, Sorrow, and the Feeling Brain. Orlando, FL: Harcourt Brace, 2003. ISBN: 9780156028714.
Cahill, Larry. "Sex-related Influences on the Neurobiology of Emotionally Influenced Memory." Annals of the New York Academy of Sciences 985 (2003): 163-173.
Kandell, Eric, et al. Principles of Neural Science, pp. 982-997.
Phelps, Elizabeth A., et al. "Activation of the Left Amygdala to a Cognitive Representation of Fear." Nature Neuroscience 4 (2001): 437-441.
Thompson, Clive. "There's a Sucker Born in Every Medial Prefrontal Cortex." New York Times Magazine, October 26, 2003, pp. 54-57.
Mobbs, Dean, Michael D. Greicius, Eiman Abdel-Azim, Vinod Menon, and Allen L. Reiss. "Humor Modulates the Mesolimbic Reward Centers." Neuron 40 (2003): 1041-1048.
Damasio, Antonio R., et al. "Subcortical and Cortical Brain Activity during the Feeling of Self-generated Emotions." Nature Neuroscience 3 (2000): 1049-1056.
Amaral, David G. "The Primate Amygdala and the Neurobiology of Social Behavior Implications for Understanding Social Anxiety." Biological Psychiatry 51 (2002): 11-17.
20Neuroscience and Marketing: Hitting the "Sweet Spot"Required Reading
Bartels, Andreas, and Semir Zeki. "The Neural Correlates of Maternal and Romantic Love." NeuroImage 21, no. 3 (2004): 1155-1166.
McClure, Samuel M., et al. "Neural Correlates of Behavioral Preferences for Culturally Familiar Drinks." Neuron 44 (2004): 379-387.
Erk, Susanne, Manfred Spitzer, Arthur P. Wunderlich, Lars Galley, and Henrik Walter. "Cultural Objects Modulate Reward Circuitry." NeuroReport 13, no. 18 (2002): 2499-2503.
Editorial. "Brain Scam?" Nature Neuroscience 7 (2004): 683.
Thompson, Clive. "There's a Sucker Born in Every Medial Prefrontal Cortex." New York Times Magazine, October 26, 2003, 54-57.
Brammer, Michael. "Brain Scam?" Nature Neuroscience 7 (2004): 1015.

Optional Reading

Mobbs, Dean, Michael D. Greicius, Eiman Abdel-Azim, Vinod Menon, and Allen L. Reiss. "Humor Modulates the Mesolimbic Reward Centers." Neuron 40 (2003): 1041-1048.
Greene, Joshua D., R. Brian Sommerville, Leigh E. Nystrom, John M. Darley, and Jonathan D. Cohen. "An fMRI Investigation of Emotional Engagement in Moral Judgment."  Science 293, no. 5537 (2001): 2105-2108.
Amazon logo Damasio, Antonio. Looking for Spinoza: Joy, Sorrow, and the Feeling Brain. Orlando, FL: Harcourt Brace, 2003. ISBN: 9780156028714 .
21Learning and Memory: The Case of HM

Required Reading

Purves, Dale, et al. Neuroscience. pp. 733-753.
Corkin, Suzanne, David G. Amaral, R. Gilberto Gonzales, Keith A. Johnson, and Bradley T. Hyman. "H.M.'s Medial Temporal Lobe Lesion: Findings from Magnetic Resonance Imaging." Journal of Neuroscience 17, no. 10 (1997): 3964-3979.
Wagner, Ullrich, Steffen Gais, Hilde Haider, Rolf Verleger, and Jan Born. "Sleep Inspires Insight." Nature 427 (2004): 352-355.

Optional Reading

Ellenbogen, Jeffrey M., et al. "Interfering with Theories of Sleep and Memory: Sleep, Declarative Memory, and Associative Interference." Current Biology 16, no. 13 (2006): 1290-1294.
Cabeza, R., and L. Nyberg. "Imaging Cognition II: An Empirical Review of 275 PET and FMRI Studies." Journal of Cognitive Neuroscience 12 (2000): 1-47.
Kandell, Eric, et al. Principles of Neural Science. pp. 122-146.
Siegel, Jerome M. "Why We Sleep." Scientific American 289 (2003): 92.
22Structure and Function of Brains with Superior Memory

Required Reading

Maguire, Eleanor A., Elizabeth R. Valentine, John M. Wilding, and Narinder Kapur. "Routes to Remembering: The Brains behind Superior Memory." Nature Neuroscience 6 (2002): 90-95.
Maguire, Eleanor A., et al. "Navigation-related Structural Change in the Hippocampi of Taxi Drivers." Proceedings of the National Academy of Sciences 97, no. 8 (2000): 4398-4403.
Dehaene, S., E. Spelke, P. Pinel, R. Stanescu, and S. Tsivkin. "Sources of Mathematical Thinking: Behavioral and Brain-imaging Evidence." Science 284, no. 5416 (1999): 970-974.

Optional Reading

Johannes, Laura. "Finding Alzheimer's Early; Doctors Divided over the Need for an Expensive PET Scan in Diagnosis of Brain Disease." Wall Street Journal, October 16, 2003, B1.
Kandell, Eric, et al. Principles of Neural Science. pp. 122-146.
McMahon, Pamela M., Sally S. Araki, Eileen A. Sandberg, Peter J. Neumann, and G. Scott Gazelle. "Cost Effectiveness of PET in the Diagnosis of Alzheimer Disease." Radiology 228 (2003): 515-522.
Rundle, Rhonda L. "MRI Is Used to Predict Memory Loss." Wall Street Journal, November 25, 2003, D4.
Rusinek, Henry, et al. "Regional Brain Atrophy Rate Predicts Future Cognitive Decline: 6-year Longitudinal MR Imaging Study of Normal Aging." Radiology 229 (2003): 691-696.
Petrella, Jeffrey R., R. Edward Coleman, and P. Murali Doraiswamy. "Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future." Radiology 226 (2003): 315-336.
Rosen, Allyson C., Arun L. W. Bokde, Allison Pearl, and Jerome A. Yesavage. "Ethical and Practical Issues in Applying Functional Imaging to the Clinical Management of Alzheimer's Disease." Brain and Cognition 50, no. 3 (2002): 498-519.
23How Emotion and Antidepressants Affect Memory

Required Reading

Van Stegeren, Anda H., et al. "Noradrenaline Mediates Amygdala Activation in Men and Women during Encoding of Emotional Material." NeuroImage 24, no. 3 (2005): 898-909.
Pesenti, Mauro, et al. "Mental Calculation in a Prodigy Is Sustained by Right Prefrontal and Medial Temporal Areas." Nature Neuroscience 4 (2001): 103-107.
Harmer, Catherine J., Nicholas C. Shelley, Philip J. Cowen, and Guy M. Goodwin. "Increased Positive versus Negative Affective Perception and Memory in Healthy Volunteers Following Selective Serotonin and Norepinephrine Reuptake Inhibition." American Journal of Psychiatry 161 (2004): 1256-1263.
24Depression, Anxiety and Psychosis

Required Reading

Purves, Dale, et al. Neuroscience, pp. 704-705 (Box E), p. 148 (Box C), p. 625 (Box B).
Bejjani, Boulos-Paul, et al. "Transient Acute Depression Induced by High-frequency Deep-brain Stimulation." New England Journal of Medicine 340, no. 19 (1999): 1476-1470.
Begley, Sharon. "New Hope for Battling Depression Relapses: Study Illuminates Why the Benefits of Therapy Are More Lasting Than Medication." Wall Street Journal, January 6, 2004, D1.
Santarelli, Luca, et al. "Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants." Science 301 (2003): 805-809.

Optional Reading

Purves, Dale, et al. Neuroscience, pp. 403 (Box B).
Kandell, Eric, et al. Principles of Neural Science, pp. 982-997.
D'Sa, Carroll, and Ronald S. Duman. "Antidepressants and Neuroplasticity." Bipolar Disorders 4, no. 3 (2002): 183-194.
Amaral, David G. "The Primate Amygdala and the Neurobiology of Social Behavior Implications for Understanding Social Anxiety." Biological Psychiatry 51 (2002): 11-17.
25Vision, Memory and Feelings: Binding them Together

Required Reading

Purves, Dale, et al. Neuroscience. pp. 613-618, 623-636.
Nitschke, Jack B., et al. "Orbitofrontal Cortex Tracks Positive Mood in Mothers Viewing Pictures of Their Newborn Infants." NeuroImage 21, no. 2 (2004): 583-592.
Santarelli, Luca, et al. "Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants." Science 301 (2003): 805-809.

Optional Reading

Morris, J., et al. "A Different Neural Response in the Human Amygdala in Fearful and Happy Facial Expressions." Nature 383, no. 81 (1996): 812-815.
Sacks, Oliver. "A Walking Grove," and "Rebecca." In The Man Who Mistook His Wife for a Hat. pp. 187-194, 178-186.
26Music, Math and the Brain

Optional Reading

Pascual-Leone, Alvaro. "The Brain that Plays Music and Is Changed by It." Annals of the New York Academy of Sciences 930, no. 1 (2001): 315-329.
Gaser, Christian, and Gottfried Schlaug. "Gray Matter Differences between Musicians and Nonmusicians." Annals of the New York Academy of Sciences 999, no. 1 (2003): 514-517.
Zatorre, Robert J. "Music and the Brain." Annals of the New York Academy of Sciences 999, no. 1 (2003): 4-14.
Schlaug, Gottfried. "The Brain of Musicians: A Model for Functional and Structural Adaptation." Annals of the New York Academy of Sciences 930, no. 1 (2001): 281-299.
Annals of the New York Academy of Sciences 930, June 2001. Issue devoted to this subject.
 Consciousness / NeuroeconomicsConsciousness, The Permanent Vegetative State, and Public Policy

Required Reading

Purves, Dale, et al. Neuroscience. pp. 603-622.

Optional Reading

Kandell, Eric, et al. Principles of Neural Science. pp. 1316-1319.
Charatan, Fred. "Governor Jeb Bush Intervenes in 'Right to Die' Case." British Medical Journal 327 (2003): 949.
Zimmer, Carl. "What If There Is Something Going On in There?" New York Times Magazine, September 28, 2003, 52-56.
Schiff, Nicholas D., et al. "Residual Cerebral Activity and Behavioural Fragments Can Remain in the Persistently Vegetative Brain." Brain 125, no. 6 (2002): 1210-1234.
Giacino, J. T., et al. "The Minimally Conscious State: Definition and Diagnostic Criteria." Neurology 58, no. 3 (2002): 349-353.
Illes, Judy, and Thomas A. Raffin. "Neuroethics: An Emerging New Discipline in the Study of Brain and Cognition." Brain and Cognition 50 (2002): 341-344.
Council on Ethical and Judicial Affairs, American Medical Associaton. "Medical Futility in End-of-life Care." Journal of the American Medical Association 281, no. 10 (1999): 937-941.
Cantor, Michael D., et al. "Do-not-resuscitate Orders and Medical Futility." Archives of Internal Medicine 163 (2003): 2689-2694.
Report of the Quality Standards Subcommittee of the American Academy of Neurology. "Practice Parameters: Assessment and Management of Patients in the Persistent Vegetative State." Neurology 45, no. 5 (1995): 1015-1018.
Report of the Quality Standards Subcommittee of the American Academy of Neurology. "Practice Parameters for Determining Brain Death in Adults." Neurology 45, no. 5 (1995): 1012-1014.
The Multi-Society Task Force on PVS. "Medical Aspects of the Persistent Vegetative State (First of Two Parts)." New England Journal of Medicine 330, no. 21 (1994): 1499-1508.
———. "Medical Aspects of the Persistent Vegetative State (Second of Two Parts)." New England Journal of Medicine 330, no. 21 (1994): 1572-1579.
Neuroethics: Mapping the Field. 2002 Conference Proceedings, Dana Foundation.
Neuroeconomics

Required Reading

Camerer, Colin, George Lowenstein, and Drazen Prelec. "Neuroeconomics: How Neuroscience Can Inform Economics." Journal of Economic Literature 43, no. 1 (2005): 9-64.
Adolphs, Ralph. "Neural Systems for Recognizing Emotion." Current Opinion in Neurobiology 12, no. 2 (2002): 169-177.
Sanfey, Alan G., James K. Rilling, Jessica A. Aronson, Leigh E. Nystrom, and Jonathan D. Cohen. "The Neural Basis of Economic Decision-making in the Ultimatum Game." Science 300, no. 5626 (2003): 1765-1758.

Optional Reading

Wagner, Ullrich, Steffen Gais, Hilde Haider, Rolf Verleger, and Jan Born. "Sleep Inspires Insight." Nature 427 (2004): 352-355.
Adolphs, Ralph, Hanna Damasio, Daniel Tranel, Greg Cooper, and Antonio R. Damasio. "A Role for Somatosensory Cortices in the Visual Recognition of Emotion as Revealed by Three-dimensional Lesion Mapping." Journal of Neuroscience 20, no. 7 (2000): 2683-2690.
Iacoboni, Marco, Roger P. Woods, Marcel Brass, Harold Bekkering, John C. Mazziotta, and Giacomo Rizzolatti. "Cortical Mechanisms of Human Imitation." Science 286, no. 5449 (1999): 2526-2528.
Stickgold, R., J. A. Hobson, R. Fosse, and M. Fosse. "Sleep, Learning and Dreams: Off-line Memory Reprocessing." Science 294, no. 5544 (2001): 1052-1057.
Bartels, Andreas, and Semir Zeki. "The Neural Basis of Romantic Love." NeuroReport 11, no. 17 (2000): 3829-3834.
Holden, Constance. "Imaging Studies Show How Brain Thinks about Pain." Science 303, no. 5661 (2004): 1121.
Santarelli, Luca, et al. "Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants." Science 301 (2003): 805-809.
Simos, P. G., et al. "Dyslexia-specific Brain Activation Profile Becomes Normal Following Successful Remedial Training." Neurology 58 (2002): 1203-1213.
Semir, Zeki. Inner Vision: An Exploration of Art and the Brain.
 Can Thinking Prevent Dementia?

Required Reading

Wilson, Robert S., et al. "Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease." Journal of the American Medical Association 287, no. 6 (2002): 742-748.
Verghese, Joe, et al. "Leisure Activities and the Risk of Dementia in the Elderly." New England Journal of Medicine 348, no. 25 (2003): 2508-2516.
Ball, Karlene. "Effects of Cognitive Training Interventions with Older Adults: A Randomized Controlled Trial." Journal of the American Medical Association 288, no. 18 (2002): 2271-2281.
Coyle, Joseph T. "Use It or Lose It - Do Effortful Mental Activities Protect against Dementia?" New England Journal of Medicine 348, no. 25 (2003): 2489-2490.

Optional Reading

Cabeza, R., and L. Nyberg. "Imaging Cognition II: An Empirical Review of 275 PET and FMRI Studies." Journal of Cognitive Neuroscience 12 (2000): 1-47.
Churchill, James D., et al. "Exercise, Experience and the Aging Brain." Neurobiology of Aging 23 (2002): 941-955.
 
 

Lecture Notes

SES #TOPICSLECTURE SUMMARIES
1Brain Anatomy and ImagingBrain as seat of consciousness: Historical introduction - Greeks, Descartes, 19th Century phrenology; British neurologist Hughlings Jackson and the modern era.
Overview of the regional anatomy of the brain and spinal cord:
The regions of the human brain that serve motor and sensory functions, vision, hearing, smell, coordination, language, memory and emotion
Cerebral cortex and white matter
Brain stem and cerebellum
Thalamus and Hypothalamus
Basal ganglia
Ventricles
Cranial nerves
A quick tour of the regional anatomy of the brain is introduced using figures, computerized axial tomography (CT) images, and magnetic resonance images (MRI) from normal subjects and individuals with strokes and other diseases to illustrate brain function.
2Cells and Brain Imaging 
3Synaptic PotentialsA general knowledge of the cellular basis of brain function is essential to understanding how drugs such as antidepressants, memory enhancing drugs, or stimulants such as Ritalin work. We will review:
Neurons and supporting glia
Axons: How neurons carry information from one part of the nervous system to another
Axons and their surrounding insulation: The myelin sheath
Synapses: How neurons communicate with one another
Resting membrane potential: How neuronal membranes maintain a charge with the outside positive relative to the inside
Action potential: How depolarization of the resting membrane potential results in a reversal in the charge of the membrane with the exterior becoming negative relative to the interior. How the action potential is propagated along the axon and how information is communicated along the axon up to 2 meters in length. How does synaptic transmission occur?
The following will be discussed:
Excitatory and inhibitory synapse
Release of neurotransmitters and neuromodulators from presynaptic neurons
Re-uptake of neurotransmitters
The neuromuscular junction
Classes of neurotransmitters and neuromodulators:
Acetylcholine, amino acids, monoamines and peptides

Clinical Correlation

Have you wondered what happens when you hit your "funny bone" or why your leg gets numb from crossing your legs? A common cause of fish poisoning in the tropics is due to a neurotoxin: Ciguatera poisoning from fish consumption. Seizures are caused by abnormally excitable nerve cell membranes. Some anti-seizure medications block membrane sodium channels and stabilize membranes. Seizures may cause involuntary movements or experiences e.g., olfactory and auditory hallucinations, deja vu, and other complex behaviors. See: Singing Seizure Video Neurotransmitters are chemicals which are released by one neuron, the presynaptic neuron, and pass across the synaptic cleft to stimulate the post-synaptic neuron. The post-synaptic neuron can be stimulated (depolarized) or inhibited (hyperpolarized) by the neurotransmitter. Increasing or decreasing the concentration of the neurotransmitter, therefore, can increase or decrease its effect on the post-synaptic neuron.
Some diseases have a deficiency of a specific neurotransmitter. For example, in Parkinson's disease there is a deficiency of dopamine in a specific pathway in the brain. In Alzheimer's disease there is a deficiency of acetylcholine. In these two cases drugs are administered to patients to increase the concentration of these deficient neurotransmitters. In the case of depression, there is a deficiency of serotonin and norepinephrine. Antidepressants have been developed which will increase the concentration of these neurotransmitters. Early antidepressants, such as tricyclic antidepressants, increase the concentration of both of these neurotransmitters. In the past decade serotonin reuptake inhibitors (SSRI) such as Prozac have dominated the antidepressant market. As the article from the WSJ above indicates there is again a debate over the relative importance of these two neurotransmitters in depression.
Readings from Oliver Sacks illustrate "how we know our bodies in space" and how we compensate when we lose one or more of our senses. In order to have an image of "where we are in space" our brain integrates information from our visual system, vestibular system (labyrinth of inner ear), and position sense of musculoskeletal system (proprioception). Information from each of these is integrated which leads to a "map of space" and where our bodies are in that space. Aberration of one of these inputs creates a disorienting experience. For example, alcohol impairs the vestibular system causing incoordination, staggering and falling. In diseases of the eyes, inner ear or nervous system there may be impairment of one of these inputs which leads to spatial disorientation. Some of Dr. Sacks's cases illustrate how brain plasticity permits one to overcome loss of function of one of these sensory inputs.
4fMRI of the Human Brain
Prof. John Gabrieli, MIT
 
5Seeing and Reading OthersThe capacity to "read" another person's emotional status, predict what they will do next or recognize what they think that you are thinking represent among the most important talents of the human brain. In a society where human interaction often determines success such abilities are highly valued. How does the human brain recognize the facial emotions of others or the sarcasm of a voice? It turns out that the neural systems responsible for recognizing facial and aural emotional content relies on the right cerebral hemisphere to a greater extent than the left where grammar and semantic meaning of words are stored.
6Cognitive Enhancement through Neuropharmacology

Clinical Correlation

The brains of patients with Alzheimer's disease have a reduced amount of neurotransmitter acetylcholine. With our understanding of synaptic transmission, scientists have been able to develop drugs which increase the amount of acetylcholine available and modestly improve memory in Alzheimer's patients. A recent study has shown that such drugs also work in normal individuals (Yesavage). Additionally, a race among several biotechnology companies now exists to develop memory enhancement drugs to improve normal human cognition (See "Quest for a Smart Pill"). It has been said that other drugs such as methylphenidate (Ritalin), which is prescribed for attention deficit disorder, have been used without a prescription as memory enhancing drugs. Such uses in normal individuals have unknown long term medical consequences and create ethical issues as do the use of steroids in athletes. (Possible final paper topic).
Other clinical examples of drugs which affect neurotransmitter function are serotonin reuptake inhibitors (e.g. Prozac) which increases serotonin and alleviates depression but also may act by inducing neurogenesis. Antidepressants are widely accepted and improve memory in depressed patients since impaired memory is a common feature of depression. Does the role that antidepressants play in the modification of the brain affect the debate in regard to the use of memory enhancing drugs?
7Oxytocin and Trust, Antidepressants and Neurogenesis 
8Neurogenesis: Teaching Old Dogs New TricksA surprising discovery in the last few years in neurobiology has been that neurons are born, neurogenesis, in the adult mammalian brain. Initially, this had been shown in animals and, more recently, in the humans hippocampus, the site of declarative memory formation. (See Greenough). Furthermore, the rate of neurogenesis in animals has been enhanced by experience, both physical activity and living in enriched environments (See Scientific American article by Gage). Provocative clinical human studies suggest that memory loss (dementia) can be forestalled by rich cognitive activities e.g. board games, crossword puzzles. These animal and clinical studies may lead to a strategy for preventing dementia in humans.
9Test 1 
10Critical Periods: Implications for EducationThe nervous system has a structural organization which is genetically determined to some degree but in order for the brain to develop normally, it requires experience. This is called experience-dependent brain development. An example is the child born with a cataract. If the cataract is not removed at an early age the person will never develop normal vision in the affected eye even if it is removed later. Alternatively, a person who acquires a cataract as an adult can have the cataract removed many years later and have normal vision after it is removed. The difference in outcome is due to the "critical period" of the visual system development in childhood. Neurobiological studies have shown that opportunities exist for brain development in childhood and that once the window of opportunity closes, it never reopens. The mechanism of this is being elucidated at a molecular level and is a major area of research. The implications for childhood development, public policy and educational programs are enormous; because, as outlined in subsequent classes, for many skills we seem to have an opportunity to learn at a young age which then closes later. For example, in the case of learning a foreign language with a native accent the window of opportunity closes at about puberty in most individuals.
The articles by Christakis and Penn and Schatz demonstrate that the consequences of early experience have long-lasting behavioral and structural consequences. Throughout early childhood a much larger number of synapses form than ultimately exist in the adult. This is because those synapses which are 'used' in childhood survive and are strengthened at the expense of unused synapses which are pruned and die back during later childhood and adolescence; The 'used', and retained, synapses follow the rule first enunciated by Hebb, "neurons that fire together wire together."
Critical periods of brain development provide opportunities to permanently alter the brain wiring. Furthermore, knowledge of brain development provides a basis upon which to define educational programs. For example, the acquisition of a second language before puberty generally results in a native accent, whereas, learning a foreign language after puberty usually results in a foreign accent. The article by Kim demonstrates that when a second language is learned during early childhood the same region in Broca's area (left frontal lobe) is used for both native and second language; alternatively, when the second language is learned later in life, the second language is located in a region adjacent but not superimposed to the native language. Accent may be one of the phenotypic expressions of this difference in localization.
11Neuroplasticity in the AdultPrimary motor cortex in the frontal lobe is organized in such a way that the left side of the brain controls the right body and that the foot neurons are near the crown of the head and the hand is midway between the crown and the ear and the mouth is just above the ear (Homunculus). These neurons control individual movements according to this motor map of the cerebral cortex. The map was first discovered by Dr. Wilder Penfield a neurosurgeon who stimulated the brain in awake patients undergoing epilepsy surgery. He was able to map different parts of the brain to different motor and sensory functions. The premotor cortex lies in front (anterior) to the motor cortex and its role is to plan voluntary movements. It is activated in mental rehearsing of a movement such as piano playing or pole vaulting before the actual execution.
Several studies have shown that even in adulthood the motor map of the brain can be modified. Studies in animals have shown that increased finger use enlarges the area of the "brain real estate" devoted to those fingers. In humans, Elbert has shown in string players that the size of the brain cortex, on the right side of the brain, devoted to the left hand is enlarged. Alternatively, if a finger or limb is amputated the adjacent functional areas "invade" the unused area and make use of it; another example of competition between neurons and the adage "use it or lose it". Recent studies using a technique called constraint behavior therapy actually limits the use of a good limb to increase the function of the impaired limb such as in cases of cerebral palsy with promising results. This is an example of basic science leading to important clinical discoveries and benefits to patients.
12Language, Dyslexia and Universal GrammarLanguage which includes both oral and written forms of communication is lateralized to the left cerebral hemisphere in nearly all right-handed individuals and in most left-handed individuals. Disturbance of language function is called aphasia. When reading alone is disturbed it is termed dyslexia. Recent fMRI studies show that in dyslexia both cerebral hemispheres are activated (Simos). When children undergo successful treatment, activation is normalized to the left cerebral hemisphere.
Functional imaging of the brain (fMRI) has permitted linguists to study the structure of language. Universal grammar has been proposed as an underlying structure of all languages. Recent studies have shown that if one learns a new foreign language with native grammar, Broca's area, the region of the brain needed to use grammar, is engaged. However, if the new foreign language is learned with an artificial grammar, Broca's area is not engaged to speak the new language; rather other areas of brain are used and the subjects have difficulty learning the new language. The findings of this study have been used as evidence to support the argument of universal grammar.
13Visual System IThe visual system is the most studied system in the cerebral hemispheres and information learned here is often used as a model for understanding other systems such as auditory, olfaction, limbic, motor, and sensory. Visual information is relayed from the retina to the primary visual cortex of the occipital lobe. However, visual images achieve meaning when they are then analyzed in the adjacent parietal and temporal lobes. Because it is in these areas that remembered patterns, engrams, are stored from prior experience. For example the left temporal lobe is the site of recognizing letter symbols as words in reading; the right temporal and parietal lobes "contain the maps" and injury to this area can lead to topographic agnosia, such as the inability to find one's way in one's own house; injury to the undersurface of the temporal lobe can lead to inability to recognize faces, prosopagnosia. While we were able to localize these functional regions of the brain because patients with injuries to certain areas would manifest specific deficits (see Bisiach and Luzzatti above), we can now use functional imaging to study normal brain physiology in healthy individuals.
Injury to the right side of the brain can result in neglect of the left side of the body or the entire left side of internal and external space. The case of the man who mistook his wife for a hat, which illustrates this phenomenon, will be discussed.
14Visual Neglect and ProsopagnosiaThe left temporal lobe is the site of recognizing letter symbols as words in reading; the right temporal and parietal lobes "contain the maps" and injury to this area can lead to topographic agnosia, such as the inability to find one's way in one's own house; injury to the undersurface of the temporal lobe can lead to inability to recognize faces, prosopagnosia. While we were able to localize these functional regions of the brain because patients with injuries to certain areas would manifest specific deficits (see Bisiach and Luzzatti above), we can now use functional imaging to study normal brain physiology in healthy individuals.
Injury to the right side of the brain can result in neglect of the left side of the body or the entire left side of internal and external space. The case of the man who mistook his wife for a hat, which illustrates this phenomenon, will be discussed.
15Rembrandt, Leonardo, Monet: How we See ThemThe most sophisticated image processor imaginable, the brain uses several techniques to see. Among those that have been best studied, the visual system can sharpen borders and localize objects in space. We are beginning to understand some of these mechanisms. For example, an on-off (on-center and off-surround) organization of neurons from the retina to the primary visual cortex causes light objects bordered by dark objects to appear brighter than when they are not bordered by dark objects. An illustration would be a Rembrandt etching where a window is surrounded by darkness appears whiter or brighter than the paper it is printed on. In this case, the center-surround organization of the retinal cells and the visual cortex cause the light-stimulated neurons to actually have more activity (action potentials) when the surrounding cells are inactive than when the surrounding cells are stimulated.
In the example of the "where pathway" in the parietal lobe, contrast in luminance (value in art parlance) is used to identify the location of things (Livingstone). When the contrast in luminosity of adjacent colors is low, the parietal lobe has difficulty in identifying where something is in relation to its surroundings. When the contrast in luminosity is high the parietal lobe can readily localize objects in relation to one another. Renaissance artists used high contrast in luminosity to create the appearance of mass and volume. In fact, Leonardo wrote about the importance in using paint with high contrast in order to create the appearance of volume. Michaelangelo used extreme contrasts in luminance to create massive figures. Alternatively, Impressionists such as Monet attempt to paint light and movement and avoid mass. They use subtle variation in luminance in order to achieve this effect. Modern artists use this knowledge to create visual illusions and "tricks." By studying different paintings we shall explore how differences in luminance are interpreted by the brain and thus how the brain works. (See Livingstone for discussion)
16Sensory System and PainSensations from different regions of the body travel to different regions of the brain. This brain map is called a homunculus since the cartoon of the cerebral cortex illustrating different body regions looks like a person; foot at the crown, hand in the middle and face at the bottom of the parietal lobe. The homunculus can be modified based upon experience in both the child and the adult. Practicing piano changes the homunculus hand region in the brain. Cortical mapping studies of the homunculus in humans with syndactyly (fused fingers at birth) and experimental cortical mapping studies in monkeys will be discussed. Phantom limb syndromes (sensations experienced in amputated limbs) demonstrate the effect of amputation on the cortical map. These studies demonstrate that the homunculus is "plastic" or modifiable and have profound implications for teaching us how the brain learns. These studies also reveal the opportunities to improve function in the healthy and the brain injured.
The sensation of pain includes both the sensory component as well as the emotional or suffering component. The sensory component is found in the thalamus and the parietal cortex, the somatosensory cortex. The emotional or suffering element of the experience has been reported to be in the anterior cingulate cortex, a region of brain within the limbic system. The limbic system is phylogenetically an old part of our brain and is concerned with emotions and feelings. Individuals who feel pain but do not experience the suffering or affective component of pain have been shown to have diminished activity in the anterior cingulate gyrus.
17Placebo, Empathy, and Theory of MindPlacebos are inert substances which have physiological consequences. It has been reported that the placebo response to pain remedies accounts for about 30% of the responses. Recent functional imaging studies have demonstrated that the placebo response is mediated by the frontal lobe which anticipates a pain stimulus; this activates the endogenous opiate pathway in the midbrain, the periaqueductal grey, which is known to send fibers to the spinal cord blocking (gate) the entrance of pain impulses into the spinal cord. This new imaging data explains why opiate antagonists block the placebo response. Thus the placebo response and the expectancy of pain response rests on a physiological mechanism. (Wager)
Empathy is the feeling we experience when we share in the feelings of others. fMRI studies show the regions of brain which are activated during the experience of empathy. In the study by Singer, women were put in an fMRI scanner and were studied when they or their significant others were administered a painful stimulus. When they realized that their friend was being stimulated they showed activation of the affective region, the limbic system but not the sensory region of their own brains.
18Test 2 
19Emotions and Feelings: Romantic and Maternal LoveEmotion-triggering sites of the brain are the limbic system - the amygdala, prefrontal cortex and the cingulate. Activation of these sites leads to activation of the hypothalamus which, in turn, causes visceral and musculoskeletal changes such as palpitations, goose bumps, sweaty palms, etc. Joy and sadness are associated with activation of different regions of the limbic system on fMRI. Painful stimuli also lead to activation of the limbic system. Placebos, pharmacologically inert substances, can alleviate pain in many individuals, which has been claimed to mean that the pain was imaginary. However, the placebo response is blocked by opiate antagonists revealing that the pain is not imagined. As discussed in the pain class, activation of the periaqueductal grey matter by placebos can block (gate) the entry of pain impulses in the spinal cord.
Bartels et al. report that they have found the regions of brain activated during the experience of recently realized romantic love. As discussed in a later class, this is different from the region of brain activated in maternal love.
20Neuroscience and Marketing: Hitting the "Sweet Spot"Why are emotionally charged experiences remembered so well? Why does one sometimes get an unconscious feeling that someone is staring? The answer may be that the amygdala which sits near the hippocampus is activated when we are confronted with frightening experiences such as threatening facial expressions. In addition, if threatening expressions are visually presented to us for a few milliseconds which is too short to consciously see the image, the amygdala is activated as well. There is a visual pathway to the amygdala from the thalamus which does not pass through the visual cortex and thus the image does not reach consciousness. Advertisers and other marketers can use this to influence people's emotions when presenting other information i.e., associating a product with the feeling of fear or joy at an unconscious level. Alternatively, the prefrontal cortex is reported to be the site stimulated when one feels the need to have an object. Advertisers are taking notice and a field of "neuroadvertising" is developing; see Thompson, NYT magazine.
Emotionally-charged experiences are remembered more readily than others; consider 9/11. These memories are stored through both the hippocampus and limbic system. Drugs such as adrenergic blockers and benzodiazepines can block this effect. Some have tried to "unmake" emotionally charged memories through the use of drugs that block neurotransmitters in the limbic system. See Unmaking memories.
Why we sleep is unknown. But according to a report in Nature this year, it may pay to "sleep on it." Wagner et al. report that subjects who were presented a problem and then slept did better in solving the problem than if they did not sleep afterwards.
21Learning and Memory: The Case of HMMemory has been classified as explicit and implicit. Explicit memory is that for facts, dates, locations and the like. Examples of implicit memory are procedures and priming. Explicit memory requires the hippocampus for encoding new information. A tragic incident involving a man known as HM occurred when both his hippocampi were removed over 50 years ago in an effort to treat his epilepsy. It was not known that he would lose the ability to encode new memories. He thus can recall events in detail from before the surgery such as World War II but cannot recall people he has met repeatedly for the past 50 years. We shall discuss his findings including his MRI.
22Structure and Function of Brains with Superior MemoryExplicit memories are stored in multiple locations distributed throughout the cerebral cortex. For example, spatial memories localize to the right cerebrum. Furthermore, experienced taxi drivers are reported to have larger right hippocampi than controls (Maguire). Recall of words activates the left hippocampus (Maguire). Individuals with superior memories often use a technique known for over 2500 years as the "Method of Loci" whereupon facts are related to locations. When these superior memorizers demonstrate their skill and undergo fMRI studies, the right cerebral hemisphere which is associated with spatial localization is activated, thereby corroborating the technique they report that they use.
The hippocampus is needed to acquire new explicit memories, as shown with HM. Alzheimer's Disease affects the hippocampus early in the disease process and not unexpectedly, memory loss for recent events is a dominant symptom. Although treatment with drugs which increase the neurotransmitter acetylcholine provide modest symptom relief, there is no cure or way of stemming the disease progression. There are, however, new imaging techniques which claim to diagnose the disease through reduced metabolism in certain brain regions, parietal lobes, or showing progressive atrophy of the hippocampi. Currently Medicare will not pay for these procedures. These tests have a high incidence of false positive results as well as false negative results. We will discuss specificity, false positive rate, and sensitivity, false negative rate; an inherent problem in all diagnostic tests in medicine. The question "Should Medicare pay for imaging to diagnose Alzheimer's disease?" is a possible final paper topic.
23How Emotion and Antidepressants Affect MemoryAs common experience reveals, our recall for emotionally salient events is far superior to that of emotionally neutral experiences. The article by van Stegeren reveals that as in the case of blindsight the limbic system (amygdala in particular) is actively engaged in encoding emotionally charged experiences with both positive and negative valence. In addition, norepinephrine appears to be a major neurotransmitter necessary for this to occur. Administration of beta antagonists have been reported to mitigate the enhanced recall of emotionally charged experiences and are being investigated as a treatment to prevent post traumatic stress disorder. van stegeren and colleagues show through fMRI studies that activation of the amygdala occurs when emotionally charged material is presented to subjects. Moreover, the amygdala is attenuated with the administration of beta antagonists and the enhanced recall is diminished. Several corollary questions arise from these observations. Could memory be enhanced by stimulation of the norepinephrine system? It is known that tricyclic antidepressants which inhibit the reuptake of norepinephrine improve memory in depressed patients. Is this accomplished through this pathway or another pathway? Could other beta agonists be used in normal individuals as memory enhancing drugs? This article and the references cited emphasize the intimate interaction of the "rational" and "emotional" brain discussed in the neuroeconomics paper in the first classes.
24Depression, Anxiety and PsychosisNeuropsychiatric disorders such as anxiety and depression affect millions of Americans. Tens of billions of dollars are spent on the treatment of these disorders annually. Historically, psychoanalysis and behavioral therapies dominated the treatment milieu. In the past three decades, based upon our increased understanding of neurotransmitters, pharmacologic treatment has emerged as the dominant intervention in the medical community. However, pharmacologic and cognitive behavioral treatments are debated as to their relative efficacy. New imaging studies in the treatment of depression reveal that pharmacologic and cognitive behavioral therapies may work in different ways and have different durations of benefit. The study in Arch Psych 2004 above indicates that cognitive behavioral therapy has a more durable response. The debate is not showing any signs of resolution.
A case report by Bejjani of a patient undergoing brain surgery with deep brain stimulation resulted in a depressive manifestations and feelings reported by the awake patient. It is an interesting article because it demonstrates that electrical activity in the brain is the cause of depressive manifestations and not the effect.
Psychosis such as schizophrenia has been postulated in some cases to be due to an excess of monoamine neurotransmitters in selected pathways in the brain. This is based upon the observation that monoamines, such as dopamine, and drugs which cause an increase in monamines, such as LSD, cause psychosis. Alternatively, antidopaminergic drugs can effectively treat psychosis. Another example is in patients given the precursor to dopamine, L-DOPA, who can develop psychosis as seen in the movie, Awakenings, by Dr. Oliver Sacks.
25Vision, Memory and Feelings: Binding them TogetherWhen viewing a facial expression in a painting or a person, we often share a complex array of feelings and emotions. This is sometimes called "emotional contagion." While empathy for pain activates the cingulate gyrus, fMRI studies now show us that the perception of facial expression of disgust activates the insula, the site of disgust activation when we personally experience it. In addition, the amygdala, a portion of the limbic system anterior to the hippocampus in the temporal lobe, is activated when viewing fearful and happy faces although the two patterns are different. Finally, the overwhelming love that a mother feels when she is viewing a photo of her newborn baby has been found to be associated with activation of the orbitofrontal cortex. Of interest, this is a different activation region from that seen in couples who are recently romantically involved; which provides a basis for the argument that there are different forms of love.
26Music, Math and the BrainMusicians with perfect pitch show unique activation of the brain. We will see how fMRI has revealed how the organization of the brain is modified by training and rehearsal. For example, we will see that the area of brain which allows our fingers to move and feel is reorganized in musicians who rehearse intensively (Schlaug). Indeed even mental rehearsing has been shown to cause the brain circuits to reorganize while at the same time improving performance (Pascual-Leone). Math prodigies show unique activation of the brain when performing calculations (Presenti).
 Additional Topic: Consciousness / Neuroeconomics

Consciousness, The Permanent Vegetative State, and Public Policy

The "What if" and the "Governor Bush" articles (cited above) raise issues about consciousness and when patients should be allowed to die. Unlike brain death, the permanent vegetative state can last for years. The vegetative state has been a clinical diagnosis based upon the neurological examination (See Practice Parameter). However, functional imaging has suggested that there are "islands" of the cerebral cortex that are functioning at more than 50% of normal. However, 'binding' of multiple areas of brain (not just isolated islands) appears to be necessary for there to be consciousness. Nonetheless, these findings are generating a debate as to whether these patients should be permitted to die and whether there is more hope that they are conscious than had been thought. In addition, there is now a new diagnosis which has been proposed, "the minimally conscious state." These complex medical issues have enormous personal, ethical, societal and legal implications as we grapple with patient management decisions.

Neuroeconomics

The brain provides the means by which we have thoughts, memories, reason, feelings, emotions, motor and sensory skills and social interaction. Many fields are emerging which undertake the study of the brain in order to better understand their own discipline. Examples of these fields have been termed neuro-esthetics, neuro-linguistics, neuro-ethics and neuro-economics. Neuro-economics is a fascinating field because it endeavors to understand both the rational and emotional components of social interactions (economics) which take place among people through study of the brain. I have chosen to select a paper on neuro-economics in order to introduce the concept that the human brain has both rational and emotional components which affect one another. Through functional imaging of normal subjects and patients with specific brain lesions we can learn how the brain works as illustrated by economic or social consequences. The brain contains about 100 billion neurons (nerve cells). These neurons are connected to one another at microscopic sites called synapses to form circuits. Neurons work in groups so that many neurons and synapses will function together in a circuit when the brain is undertaking a certain task. In order for neurons to function a large amount of energy requiring oxygen and glucose is necessary to maintain electrical gradients across their membranes.
The brain is organized in such a way that different regions serve different functions. For example, there is a visual area that is used to see and a motor area which is used when executing a movement. There is even an area that plans the movement before it is actually executed. In the visual system there are associated areas which relate the visual information to previously learned information. When new information matches previous information it is recognized and recalled; sometimes with an emotional component, as when we see a loved one, which arises from a different part of the brain, the limbic system. Since this process requires abundant energy, there is an increase in blood flow, to carry oxygen and glucose, to the regions of brain that are doing the additional work. Since MRI can measure blood flow, we can map blood flow and thereby map the function of different regions of the brain when the subject is performing specific tasks. The technique called functional MRI (fMRI) has emerged in the past decade and has provided an enormous amount of new information about the functioning of the normal brain. Prior to this neurologists and other neuroscientists were dependent upon damage to the brain to determine its functional organization. Other techniques such as PET can be used to measure blood flow but require the administration of a radioactive isotope. However, one advantage of PET is that we can also measure transmitter function at synapses through the use of radio-isotopes. Another technique, magnetoencephalography (MEG) measures brain electrical activity directly and has also been used. Throughout the course we will read articles which use these new technologies to study how the brain is activated in several behaviors, both simple as well as complex. For example as subsequent class syllabi indicate we will look at learning and memory; language, both native and foreign; dyslexia; grammar; romantic love and maternal love; fear; empathy; the organization of musicians' brains, among others.
 Additional Topic: Can Thinking Prevent Dementia?There is considerable hope, and some limited evidence, that dementia can be avoided or delayed by engaging in cognitively stimulating activities (eg. crossword puzzles). This hope relies upon the 'mutability' or plasticity of the adult brain. If such a benefit occurs it may be based upon neurogenesis or plasticity of synapses. The clinical evidence is limited and based upon observational studies (See Verghese and Wilson) for the most part. The one prospective randomized trial (Ball) showed that engaging in cognitively stimulating activities improves testing results but does not change the performance of activities of daily living. The editorial by Coyle reviews the evidence. The major limitation of these studies is the question of whether it is the cognitive activities themselves which prevent dementia or whether individuals who at baseline perform more cognitive leisure activities do so because they have more cognitive reserves and, therefore, have a reduced risk of dementia. An oft-quoted retrospective study of nuns looked at the complexity of language structure which young nun novitiates had used to determine if it predicted later dementia; the authors found that those nuns which had used complex language structure had a lower late-life risk of dementia. The implication being that the ability to use complex language structure at a young age reflected increased cognitive reserves which somehow is associated with a reduced risk of late life dementia. Other studies have reported that there is a lower frequency of dementia in those with a higher level of education. Again, the mechanism of this is unknown but it is another incentive to study. For the athletes in the class, there may be an alternative; exercise has also been found in some animal studies to enhance neurogenesis. Recall that neurogenesis, which occurs in the hippocampus, may be associated with enhanced memory function. We will focus on the abstracts and the baseline characteristics of the clinical studies, including their limitations, and discuss the Coyle editorial. This clinical topic along with the animal studies from the neurogenesis literature is another suggestion for a final paper.

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