Overview and IntegrationBehavioral, Cognitive, and Clinical Neuroscience

Normal Brain AD Brain

Place Cells

PET Techniques

Neuroscience from Historical and Biographical Perspectives

Brain Hypothesis Neuron Hypothesis

For a history of neuroscienece timeline: neurolab.jsc.nasa.gov/timeline.htm

Site of Thinking: Heart, Ventricles, Brain

Phrenology and Localization of Function

Neurons as Units or a Neural Net

Jan PurkinjePurkinje cell – first viewed in 1837

Cajal and Golgi – 1906 Nobel Prize in Physiology

Santiago Ramon y CajalCamillo Golgi

Sherrington and the “Synapse”

1932 Nobel Prize in Physiology

Lashley’s Search for the Engram in the 1920s

Rats are trained to run through a maze without entering blind alleys.

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.

Donald Hebb and the Cell Assembly 1949

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

Comparative Neuroscience: Parallels in Brain-Behavior Relationships Across Species

Spatial Location

Activation maps of 2 CA1 hippocampal place cells

Fear Conditioning

Associative LearningEyeblink Classical Conditioning: Behavioral Parallels Eyeblink Classical Conditioning: Behavioral Parallels

in All Mammals Including Humansin All Mammals Including Humans

Conditioned Stimulus (CS)–Unconditioned Stimulus (US) Pairings = Conditioned Stimulus (CS)–Unconditioned Stimulus (US) Pairings = Conditioned Response (CR)Conditioned Response (CR)

Genetics, Neurobiology, and Behavior

Spatial and Temporal Control of Transgene Expression

Doubly Transgenic Mice

Region Specific Promoter tTA-Gene

tTA responsive Promoter Effector Gene

_+

Microarrays Method of examining changes in gene expression associated with event, drug, or disease

Polymerase Chain Reaction

Human Genotyping: Alipoprotein E

Anatomical and Functional NeuroanatomyTutorial: www.neuropat.dote.hu

Sulci and Gyri in the Human Brain

Ventral View of MTL

Human Limbic System

Individual Differences in Brains

Neurons, Membranes, and Electrical Potentials

Neuronal Membrane

Ion Concentration Gradients

Summation of EPSPs and IPSPs

Ion Flow in 5 Phases of the Action Potential

Synaptic Transmission and Brain Neurochemistry

Transmission at the Synapse

Brain Neurotransmitter Pathways

Drug Effects on Neurotransmission

Consciousness and Sleep

EEG Stages in Wakefulness and Sleep

Cortical Functions and Their Measurement: Vision as a Prototype

Receptive Fields

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).

Visual Attention:Color, 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).

Developmental Neuroscience

Halo response of an embryonic chick ganglion after incubation with nerve growth factor. (Courtesy of Rita Levi-Montalcini)

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.

Photographs of Human Fetal Brain Development

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

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.

Behavioral Remediation for Dyslexia: Imaging Brain Outcomes

Temple et al. (2003) PNAS, 100, 2860-2865.

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.

Emotion: Normal and Abnormal

Papez Circuit (1937)

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.

Hypofunctionality and/or Lesions of Orbitofrontal Cortex Affect Emotion

Fear Conditioning: Parallel Circuits in Humans and Rodents

Neurobiology of Memory, Memory

Impairment, and Dementia

Normal Brain AD Brain

Long Term Potentiation

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).

Synaptic Changes that Could Support Memory

Forms of Long Term Memory

Declarative Nondeclarative

•Semantic

•Episodic

•Nonassociative (sensitization and habituation)

•Procedural (Skill learning)

•Priming

•Simple Classical Conditioning

Language and Executive Function

Executive Function: Eclectic or Unified?

•Generating Ideas

•Initiating

•Inhibiting

•Planning

•Setting Goals

•Regulating and Verifying

•Temporally Ordering

In addition to Attention and Working Memory

Pseudodepression•Outward apathy and indifference

•Loss of initiative

•Reduced sexual interest

•Little overt emotion

•Little or no verbal output

Dysfunction in Orbitofrontal Cortex

Pseudopsychopathy•Immature behavior

•Lack of tact and restraint

•Coarse language

•Promiscuous sexual behavior

•Increased motor activity

•General lack of social graces

Movement and Movement Selection

Speech as an Example of Movement Selection

PET Image of Speaking a Heard Word

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

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.

Individual Variation in Lesion Sites of Broca’s, Wernicke’s, 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.

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.

Plasticity in Dyslexia as Well as Stroke

Rosen et al. (2000) Neurology, 55,1883-1894.

Temple et al. (2003) PNAS, 100, 2860-2865.