Overview and Integration

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Overview and Integration
Behavioral, Cognitive, and Clinical Neuroscience
Place Cells
PET Techniques
Normal Brain AD Brain
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Neuroscience from Historical and Biographical
Perspectives
Brain Hypothesis Neuron Hypothesis
For a history of neuroscienece timeline
neurolab.jsc.nasa.gov/timeline.htm
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Site of Thinking Heart, Ventricles, Brain
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Phrenology and Localization of Function
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Neurons as Units or a Neural Net
Jan Purkinje
Purkinje cell first viewed in 1837
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Cajal and Golgi 1906 Nobel Prize in Physiology
Santiago Ramon y Cajal
Camillo Golgi
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Sherrington and the Synapse
1932 Nobel Prize in Physiology
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Lashleys Search for the Engram in the 1920s
After training, cortical lesions are made. Three
different lesion locations are shown in red,
blue, and yellow
Errors are associated with the size rather than
the locus of the lesion.
Rats are trained to run through a maze without
entering blind alleys.
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Donald Hebb and the Cell Assembly 1949
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20th and 21st Century Advances
Electrophysiology Imaging
Genetics
EEG ERPs Multiple Unit Recording Single Unit
Recording Tetrode Recording
CT Scan MRI PET SPECT fMRI
Human genome Mouse genome Clinical
genotyping Transgenic animals Knock-out animals
MEG
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Comparative Neuroscience Parallels in
Brain-Behavior Relationships Across Species
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Spatial Location
Activation maps of 2 CA1 hippocampal place cells
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Fear Conditioning
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Associative Learning
Eyeblink Classical Conditioning Behavioral
Parallels in All Mammals Including
Humans
Conditioned Stimulus (CS)Unconditioned Stimulus
(US) Pairings Conditioned Response (CR)
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Genetics, Neurobiology, and Behavior
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Spatial and Temporal Control of Transgene
Expression
Doubly Transgenic Mice
tTA-Gene
Region Specific Promoter
tTA
_
Doxycycline

Effector Gene
tTA responsive Promoter
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Microarrays Method of examining changes in gene
expression associated with event, drug, or disease
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Polymerase Chain Reaction
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Human Genotyping Alipoprotein E
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Anatomical and Functional Neuroanatomy
Tutorial www.neuropat.dote.hu
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Sulci and Gyri in the Human Brain
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Ventral View of MTL
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Human Limbic System
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Individual Differences in Brains
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Neurons, Membranes, and Electrical Potentials
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Neuronal Membrane
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Ion Concentration Gradients
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Summation of EPSPs and IPSPs
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Ion Flow in 5 Phases of the Action Potential
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Synaptic Transmission and Brain Neurochemistry
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Transmission at the Synapse
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Brain Neurotransmitter Pathways
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Drug Effects on Neurotransmission
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Consciousness and Sleep
EEG Stages in Wakefulness and Sleep
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Cortical Functions and Their Measurement Vision
as a Prototype
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Receptive Fields
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Dorsal (Where) and Ventral (What) Visual
Streams in Human (PET)
Dorsal (where) pathway shown in green and blue
and Ventral (what) pathway shown in yellow and
red serve different functions. (Courtesy of
Leslie Ungerleider).
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Visual AttentionColor, Form, and Movement
Activation remaining after divided condition
subtracted from each of 3 focal attention
conditions. Red boxes color activation. Yellow
boxes motion activation. (Courtesy of Posner
and Raichle).
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Developmental Neuroscience
Halo response of an embryonic chick ganglion
after incubation with nerve growth factor.
(Courtesy of Rita Levi-Montalcini)
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Photographs of Human Fetal Brain Development
Lateral view of the human brain shown at
one-third size at several stages of fetal
development. Note the gradual emergence of gyri
and sulci.
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Eight Phases in Embryonic and Fetal Development
at a Cellular Level

1. Mitosis/Proliferation
2. Migration
3. Differentiation
4. Aggregation
5. Synaptogenesis
6. Neuron Death
7. Synapse Rearrangement
8. Myelination

8 stages are sequential for a given neuron, but
all are occurring simultaneously throughout fetal
development
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Recovery from Aphasia Imaging Neural Correlates
Metabolic correlates of recovery in 2 patients.
Perilesional regions near damaged left inferior
frontal gyrus identified by single subject fMRI
analysis.
Rosen et al. (2000) Neurology, 55,1883-1894.
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Behavioral Remediation for Dyslexia Imaging
Brain Outcomes
Phonological training in dyslexics who have
little or no activation in left neocortical
regions activated during reading in normal
children results in increased activation in
critical regions on the left AND increased
activation in homologous right neocortex.
Temple et al. (2003) PNAS, 100, 2860-2865.
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Emotion Normal and Abnormal
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Papez Circuit (1937)
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Orbital Frontal Cortex and Impaired Social and
Sexual Behavior
After an on-the-job explosion blew a 13-pound
tamping rod straight through Gage's head, the
well-liked construction foreman remained
conscious. He was able to talk and even walked to
the cart that took him to Cavendish, Vermont
where he was treated by Dr. John Martyn Harlow.
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Hypofunctionality and/or Lesions of Orbitofrontal
Cortex Affect Emotion
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Fear Conditioning Parallel Circuits in Humans
and Rodents
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Neurobiology of Memory, Memory Impairment, and
Dementia
Normal Brain AD Brain
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Long Term Potentiation
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Formation of New Synapses Between Neurons Showing
LTP
Electron microscopic examination of synapses
before and after undergoing LTP. Hippocampal
neurons showing increases in Ca2 also showed
doubling of spines (From Toni et al., 1999).
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Synaptic Changes that Could Support Memory
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Forms of Long Term Memory
Declarative
Nondeclarative

• Semantic
• Episodic

• Nonassociative (sensitization and
  habituation)
• Procedural (Skill learning)
• Priming
• Simple Classical Conditioning

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Language and Executive Function
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Executive Function Eclectic or Unified?
In addition to Attention and Working Memory

• Generating Ideas
• Initiating
• Inhibiting
• Planning
• Setting Goals
• Regulating and Verifying
• Temporally Ordering

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Dysfunction in Orbitofrontal Cortex
Pseudodepression
Pseudopsychopathy

• Outward apathy and indifference
• Loss of initiative
• Reduced sexual interest
• Little overt emotion
• Little or no verbal output

• Immature behavior
• Lack of tact and restraint
• Coarse language
• Promiscuous sexual behavior
• Increased motor activity
• General lack of social graces

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Movement and Movement Selection
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Speech as an Example of Movement Selection
PET Image of Speaking a Heard Word
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The Wernicke-Geschwind Model
Norman Geschwind (1974) reintroduced Wernicke's
language circuit in the mid-twentieth century,
and the Wernicke-Geschwind model of brain and
language function is still the basis for
contemporary understanding
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The Wernicke-Geschwind Model is an
Oversimplification
Binder (2003) pointed out that the supramarginal
gyrus along with the posterior superior temporal
gyrus (including the planum temporale) and the
posterior insula play a critical role in the
selection and production of ordered phoneme
sequences.
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Individual Variation in Lesion Sites of Brocas,
Wernickes, Conduction, and Global Aphasia
Composite radioisotope brain scan for patients
with each type of aphasia. Darker regions
indicate areas where the lesions of many
individual patients overlap. The isotope scans
operate on the principle that the labeled
compound can cross the blood-brain barrier in
damaged tissue but not in healthy cortical
regions.
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Dyslexia Disruption in Posterior Brain Regions
Neural systems for reading that are disrupted in
dyslexic children.
Shaywitz et al. (2002) Biol. Psychiat., 52,
101-110.
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Plasticity in Dyslexia as Well as Stroke
Rosen et al. (2000) Neurology, 55,1883-1894.
Temple et al. (2003) PNAS, 100, 2860-2865.