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The Human Brain
HOW DO WE LEARN ABOUT THE HUMAN BRAIN?
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Methods of Studying the Human Brain
Courtesy of University of Oregon Child and Family Center.
Courtesy of Marcus E. Raichle. Used with permission.
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• Lesions • Stimulation• Recording
Methods of Studying the Human Brain
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
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STROKE
© California Medical Publications. All rights reserved. This content is excluded fromour Creative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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LESIONSCauses of Brain Injury
stroke (CVA) : blood flow is disrupted
hypoxia : lack of oxygen
epilepsy : resection
degenerative disorders : Alzheimer's, Huntington’s, Parkinson’s, Korsakoff’s
tumors : abnormal cell growth
NEURONAL DEATH
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LESIONSStrengths
• Causal - brain area necessary
• Dramatic deficits: Phineas Gage, Tan, H.M., prosopagnosia
• Counterintuitive deficits: Blindsight, Category-Specific Deficits
• Dissociations
declarative memory (knowing that) & hippocampus procedural memory (knowing how) & basal ganglia
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LESIONSLimitations
• damage extensive, hard to localize, not systematic
• individual variability:
- case v.s. groups studies
• nearby systems likely to get injured together
• degeneration, recovery, compensation
• may offer limited views of normal brain functions
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Paul Broca(1824-1880)
Reprinted by permission from Macmillan Publishers Ltd:Nature Reviews Neuroscience. Source: Rorden, Chrisand Hans-Otto Karnath. "Using Human Brain Lesions toInfer Function: A Relic from a Past Era in the fMRI Age?"Nature Reviews Neuroscience 5 (2004): 812-19. © 2004.
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“Broca’s Area”: Left Precentral Gyrus of Insula
Reprinted by permission from Macmillan Publishers Ltd: Nature. Source:Dronkers, N. F. "A New Brain Region for Speech: The Insula andArticulatory Planning." Nature 384 (1996): 159-61. © 1996.
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High-Resolution MRI ofLeborgne/Tan reveals extensive medial damageincluding arcuate/superior longitudinalfasciculus
© Oxford University Press. All rights reserved. This contentis excluded from our Creative Commons license. For moreinformation, see http://ocw.mit.edu/fairuse. Source:Dronkers, N. F., et al. Brain 130 (2007): 1432-41.
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
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Stimulation
Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Source: Dalal, S. S., et al. J Neurosci Methods 174, no. 1 (2008): 106-15.
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Electrical stimulation
Pioneered by Penfield (1940s) while treating epilepsy patients
- Limited use
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STIMULATION Transcranial Magnetic Stimulation - TMS
- disrupts neural function- figure-8 wire coil- generation of magnetic field- passes through skull; induces current; neurons fire
- spatial resolution: 1.0-1.5 cm2
- sensation of scalp being withdrawn up, loud click, muscle twitches
- interferes with sensations
© IEEE. All rights reserved. This content is excluded from our Creative Commons license. For moreinformation, see http://ocw.mit.edu/fairuse. Source: Ettinger, G., et al. "Non-Invasive FunctionalBrain Mapping Using Registered Transcranial Magnetic Stimulation." Proceedings of MMBIA '96.
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STIMULATIONUses of TMS
- Motor Mapping
- Suppress neural activity
- Low-frequency stim (<1 Hz)
- Possible TX of neuropsychiatric disorders
- low-freq stim in auditory cortex of SZs decreases auditory hallucinations
- Enhance neural activity
- High-frequency stim (>1 Hz)
- i.e., faster picture naming with temporal lobe stimulation
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STIMULATIONTMS - strengths & limitations
Strengths- non-invasive
- directly assesses ± critical regions (causal)
Limitations- spread of activation- mild headache- can only go 2cm below the scalp (due to weakening of magnetic field)
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
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Structure (anatomy)
- only images anatomy
- angiography, CT, MR
- diffusion tensor imaging (DTI)
Function (physiology)
- investigates brain activity during cognitive processes
- electrical: single-cell, multi-electrode, EEG, MEG
- metabolic: PET, fMRI
RECORDINGStructure vs. Function
Public domain images.
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Anatomical Images
© source unknown. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/fairuse.
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RECORDINGStructure - MRI
Magnetic Resonance Imaging
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RECORDINGStructure - MRI resolution
- clear distinction btw white and gray matter; great spatial resolution
CT MRI© source unknown. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/fairuse.
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MRI – Lateral Views
Courtesy of Christina Triantafyllou. Used with permission.
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Huntington’s disease – post mortem
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Huntington’s disease – in vivo
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Healthy Older Individual
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Individual with Alzheimer’s Disease
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RECORDINGStructure – Brain Changes in Development
Courtesy of National Academy of Sciences, U.S.A. Used with permission. Source: Gogtay, N., et al."Dynamic Mapping of Human Cortical Development during Childhood through Early Adulthood."PNAS 101, no. 21 (2004): 8174-79. Copyright © 2004 National Academy of Sciences, U.S.A.
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Cortical Brain Growth Ages 4-21
Courtesy of National Academy of Sciences, U.S.A. Used with permission. Source: Gogtay, N., et al."Dynamic Mapping of Human Cortical Development during Childhood through Early Adulthood."PNAS 101, no. 21 (2004): 8174-79. Copyright © 2004 National Academy of Sciences, U.S.A.
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Source: Stangor, C. Introduction to Psychology. Flatworld Knowledge, 2010. Courtesy of Flatworld Knowledge.
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Medical students taking the German preliminary medical exam
Hippocampus Voxel Based Morphometry
RECORDINGStructure – Brain Changes with Learning
Source: Draganski, B., et al. J Neurosci 26, no. 23 (2006): 6314-7. © Society for Neuroscience. All rights reserved.This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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Navigation-related structural change in the hippocampi of taxi
drivers
a.
b.
c.
y = -33
y = -27
y = -20
Courtesy of National Academy of Sciences, U.S.A. Used with permission. Source: Maguire, E. A., et al. "Navigation-related Structural Change in the Hippocampi of Taxi Drivers." Proceedings of the National Academy of Sciences of the United States of America 97, no. 8 (2000): 4398-403. Copyright © 2000 National Academy of Sciences, U.S.A.
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Three-ball juggling routine 3 monthhMT/V5
RECORDINGStructure – Brain Changes with Learning
Photo courtesy of madaboutasia on Flickr.Reprinted by permission from Macmillan Publishers Ltd: Nature.Source: Draganski, B., et al. "Neuroplasticity: Changes in GreyMatter Induced by Training." Nature 427 (2004): 311-2. © 2004.
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Diffusion Tensor Imaging (DTI)
• visualizes white matter connectivity in the brain
• measures movement of water at microstructural level (microns)
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Myelinated Nerve Fiber
© Trinity College Electron Microscopy Facility (Ann Hein Lehman). License CC BY-SA. This content isexcluded from our Creative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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Diffusion anisotropy:Effects of myelination
Weak/no myelin barrier Strong myelin barrier
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DIFFERENCE IN DTI (ANISOTROPY) BETWEEN DYSLEXIC AND CONTROL GROUPS
AC = Anterior Commissure PC = Posterior CommissureCourtesy of Elsevier, Inc., http://www.sciencedirect.com. Used withpermission. Source: Klingberg, T., et al. Neuron 25 (2000): 493-500.
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Anisotropy & Reading Skill In Adults With or Without Dyslexia
Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used withpermission. Source: Klingberg, T., et al. Neuron 25 (2000): 493-500.
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Diffusion Tensor Imaging (DTI) – Tractography
red = left-right; blue = up-down; green = front-backCourtesy of Satrjit Ghosh / McGovern Institute. Used with permission.
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
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Spatial resolution: how specific can the source of signal be localized
Temporal resolution: time scale of the particular measurement
RECORDINGFunction - resolution
FunctionalMRI
TMS
Opticalimaging
MEG & ERP PETNaturally occurring
lesions
Inducedlesions
Single unit
Light microscopy
Patch clamp
Multi-unit recording
76543210-1-2-3
3
2
1
0
-1
-2
-3
-4
Millisecond Second Minute Hour Day
Brain
Map
Column
LayerNeuron
Dendrite
Synapse
Log time (sec)
Log s
ize
(mm
)
Image by MIT OpenCourseWare.
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- Electroencephalogram
RECORDINGEEG - Principles
- measures changes in electrical activity
- uses surface electrodes placed on the scalp (16-256)
- signal requires a few hundred thousandneurons to fire synchronously
Courtesy of University of Oregon Child and Family Center.
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RECORDINGEEG vs ERP
- EEG measures OVERALL brain activity - not related to stimulus presentation
- Event-related Potentials (ERP)
- averaged over trials
- time-locked to stimulus
Images of EEG and ERP waveforms removed due to copyright restrictions. See lecture video and Figures 4.24 and 4.25 in Gazzaniga, M., R. Ivry, and G. Mangun. Cognitive Neuroscience. 2nd ed. W. W. Norton & Co., 2002.
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ERPs & Language
N400 – semantic deviance; P560 – physical deviance © W. W. Norton. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/fairuse.
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RECORDINGEEG/ERP – Strengths & Limitations
Limitations
- poor spatial resolution
- records large population of neurons
- “where is (are) the signal generators?”
- many trials needed for averaging
Strengths
- great temporal resolution (10ms)
- extremely non-invasive
- relatively inexpensive
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- Magnetoencephalography
RECORDINGMEG - Principles
- active neurons produce small magnetic fields
- uses Superconducting Quantum Interference Devices (SQUIDs) to detect magnetic changes
- signals are 100 million time smaller than the earth's magnetic field
Courtesy of STAR Cryoelectronics, Susumu Matsukura (YokogawaElectric Corporation) and Gen Uehara (Kanazawa Institute ofTechnology). Used with permission.
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Reading a wordDale & Halgren,Neuron, 2000
Courtesy of Anders M. Dale. Used with permission.
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Strengths
- great temporal resolution (10ms, exactly like ERP)
- non-invasiveLimitations
- okay spatial resolution (better than ERP b/c magnetic signal does not get distorted going through skull/scalp, unlike electrical signal)
- many trials needed for averaging
- can only measure neurons parallel to the skull
- expensive ( > $1 million)
RECORDINGMEG – Strength & Limitations
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
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- Neurons require energy (oxygen and glucose)
- brain area active, increased blood flow brings energy supplies
RECORDINGMetabolic Activity
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BRAIN FACTS
- 3 1/2 pounds
- 2% total body mass
- 20% of body’s oxygen
- loss of oxygen (10 min) causes irreversible brain damage
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Cerebral blood flow Angelo Mosso - late 1880s
Resting
A = forearm; C = head/brain
Noonbells
AvaMaria?
8 x 12?
Public domain image.
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RECORDINGPET
- Positron emission tomography
- measures local variation in cerebral blood flow (CBF) correlated with mental activity (thinking about a word)
Public domain image (Wikipedia).Courtesy of Marcus E. Raichle. Used with permission.
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TASKS
+ + + + +
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TASKS+ + + + +
rose cat apple pen plane
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TASKS+ + + + +Fixation/Restrose cat apple pen planeLooking at wordrose cat apple pen planeSaying the wordrose cat apple pen planeThinking about the word - verb generation
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RECORDINGPET - Experimental Design
rose cat apple pen
Verb Generation
How to isolate region specific for verb generation?
- Use Subtraction Method:
- Find control task that differs only in the process of interest (in this case verb generation)
- Subtract out irrelevant processes © source unknown. All rights reserved. This content
is excluded from our Creative Commons license. Formore information, see http://ocw.mit.edu/fairuse.
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Hierarchical Design of the Lexical Access Experiment
Control state Stimulated state Cognitive operations
Fixation point only Passive words Passive sensory processingWord-level coding
Passive words Repeat words Articulatory codingMotor programmingand output
Repeat words Generate uses Semantic associationSelection for action
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RECORDINGImaging - Experimental Design
generating verb
reading
speaking verb
TASK CONTROL
reading
speaking verb
generating verb
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© Dr. Steven E. Petersen. All rightsreserved. This content is excludedfrom our Creative Commons license.For more information, seehttp://ocw.mit.edu/fairuse.
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RECORDINGPET - Experimental Design
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“Seeing a word” = (BOARD) - (+)© Dr. Steven E. Petersen. All rights reserved. This content is excluded from ourCreative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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© Dr. Steven E. Petersen. All rights reserved. This content is excluded from ourCreative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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Reprinted by permission from Macmillan Publishers Ltd: Nature. Source: Fink, G. R., et al. "Where in the Braindoes Visual Attention Select the Forest and the Trees?” Nature 382 (August 15, 1996): 626-8. © 1996.
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Strengths
- good spatial resolution (5-10mm); better than ERP/MEG but worse than fMRI
Limitations
- poor temporal resolution
- extremely invasive (injection of radioactive tracer)
- rare & expensive ($3 million, $700K yearly maintenance)
- correlational (not causal)
RECORDINGPET – Strengths and Limitations
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Pathology photo © Edward C. Klatt MD (from WebPath®, http://library.med.utah.edu/WebPath/);labelled adaptation by J. Crimando PhD. All rights reserved. This content is excluded from ourCreative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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© McConnell Brain Imaging Centre. All rights reserved. This content is excluded fromour Creative Commons license. For more information, see http://ocw.mit.edu/fairuse.
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Parkinson's Disease© source unknown. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/fairuse.
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Video games & dopamine
Reprinted by permission from Macmillan Publishers Ltd: Nature. Source: Koepp, M. J., et al. "Evidencefor Striatal Dopamine Release during a Video Game." Nature 393 (1998): 266-8. © 1998.
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RECORDINGfMRI
VISUAL STIMULUS
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- like MRI, take advantage of magnetic properties of molecules
- HOWEVER, focus on hemoglobin- Hemoglobins are in the blood and carry O2
- Hemoglobins become deoxygenated when O2 is absorbed
- deoxygenated hemoglobin more sensitive to magnetic field than oxygenated hemoglobin
RECORDINGfMRI Principles
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RECORDINGfMRI Principles
- increased blood flow to active region
- hemoglobins become deoxygenated as neurons use up the supplies of O2
- fMRI measures ratio of Oxy:Deoxy
- Blood Oxygenation Level Dependent effect (BOLD effect)
? If neurons using up oxygen, why does BOLD signal increase?
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RECORDINGfMRI Principles
- initial dip DOES reflect use of oxygen
- but signal too small to detect
- later rush of blood to area; arteries overcompensates, providing more oxygen than needed - MUCH LARGER SIGNAL© source unknown. All rights reserved. This content
is excluded from our CreativeCommons license. Formore information, see http://ocw.mit.edu/fairuse.
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Strengths
- good spatial resolution (2-3mm)
- non-invasive (no injection)
- widely available
- can be used to assess many cognitive tasks
Limitations
- poor temporal resolution (6s, better than PET, worse than ERP/MEG)
- expensive ($4 million, $300-$1000 per scan)
- correlational, not causal
RECORDINGfMRI - issues
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High level social cognition -
Paradigm to study Empathy
Observation or imagination of another person in a particular emotional state automatically activates a representation of that state in the observer
(Preston & de-Waal, 2002)
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EmpathyPain-sensitive activation
Pain > No Pain "self" (Experiencing)
"other" (Observing one’s partner)
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Trust Games-cooperate or defect?Ultimatum GameTwo players – split a sum of moneyProposer & ResponderRejection – no money for anyoneModal offer – 50%Low offers (20%) have 50% chance of rejection (fairness)
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EmpathyPerceived Fairness of Others
Reprinted by permission from Macmillan Publishers Ltd: Nature. Source: Singer, T., et al. "Empathic NeuralResponses are Modulated by the Perceived Fairness of Others." Nature 439 (2006): 466-9. © 2006.
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Women
Men
Feeling: Pain > No PainConj.
Seeing other: Pain > No Pain
EmpathyPerceived Fairness of Others
insula
Reprinted by permission from Macmillan Publishers Ltd: Nature. Source: Singer, T., et al. "Empathic NeuralResponses Are Modulated by the Perceived Fairness of Others." Nature 439 (2006): 466-9. © 2006.
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Nucleus Accumbens
Seeing: Pain Unfair > Pain Fair
Increase in men but not women
Men indicate stronger feelings of desire for
revenge
EmpathyPerceived Fairness of Others – Gender Differences
Reprinted by permission from Macmillan Publishers Ltd: Nature. Source: Singer, T., et al. "Empathic NeuralResponses are Modulated by the Perceived Fairness of Others." Nature 439 (2006): 466-9. © 2006.
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Terry Schiavo
Cardiac arrest Feb 25, 1990; coma, vegetative state;1998, husband petitioned to remove feeding tube;parents opposed; April 24, 2001 tube removed, but reinserted several days later; many court decisions;President Bush signed legislation to keep her alive;disconnected March 18, 2005 and died March 31, 2005
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Vegetative State
• emerge from coma, appears to be awake, but no sign of awareness• 2005, 23 year-old woman, road traffic accident, severe traumatic
brain injury, 5 months later unresponsive but preservedsleep-wake cycles
• two mental imagery testsneuroimaging - imagery activates relevant and specificperceptual and memory systems
playing tennisvisit all rooms of your house, starting with front door
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Patient and group of 12 healthy volunteers imagined playing tennis or moving around a house
Imagery-Specific Activations
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Owen et al., Science, 2006
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OUTLINE
Goals: • introduce techniques• present strengths and limitations
1) Lesion2) Stimulation3) Recording a. Structure
b. Functioni. Electrical/Magnetic
- EEG- MEG
ii. Metabolic- PET- fMRI
![Page 84: HOW DO WE LEARN ABOUT THE HUMAN BRAIN? · Methods of Studying the Human Brain Courtesy of University of Oregon Child and Family Center. Courtesy of Marcus E. Raichle. Used with permission](https://reader036.vdocuments.site/reader036/viewer/2022070703/5e793c358085ef1b260e80c7/html5/thumbnails/84.jpg)
MIT OpenCourseWare http://ocw.mit.edu
9.00SC Introduction to PsychologyFall 2011
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