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METHODS TO STUDY THE NERVOUS SYSTEM
Brain Imaging & Brain Stimulation
Techniques in Living Humans
Psychophysiological Techniques
Invasive Physiological Methods
Neuropharmacological Methods
Genetic Engineering
BEHAVIORAL METHODS IN BIOPSYCHOLOGY
Neuropsychological Testing
Behavioral Methods in Cognitive
Neuroscience
Animal Behavior Paradigms
IMAGING & STIMULATING THE LIVING BRAIN
Contrast X-rays
– cerebral angiography
Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
Positron Emission Tomography (PET)
Functional MRI (fMRI)
Magnetoencephalography (MEG)
Transcranial Magnetic Stimulation (TMS)
CT SCANS
A computer assisted X-ray procedure
An X-ray scanner is rotated 1o at a time over 180 o
Computer reconstruction
Horizontal sections
Reveal structural abnormalities, such as cortical atrophy or lesions caused by a stroke or trauma.
MRI SCANS
A strong magnetic field causes
hydrogen atoms to align in the
same orientation.
When a radio frequency wave
is passed through the head,
atomic nuclei emit
electromagnetic energy.
The MRI scanner is tuned to
detect radiation emitted from
the hydrogen molecules.
Computer reconstructs image.
MRI VS. CT SCANS
Advantages of MRI
– No ionizing radiation exposure
– Better spatial resolution
– Horizontal, Frontal or Sagittal planes
Disadvantages
– Cost
– No ferrous metal!
PET SCANS
A positron emitting radionuclide is
injected (e.g., 2-deoxyglucose).
Positrons interact with electrons
which produce photons (gamma rays)
traveling in opposite directions.
PET scanner detects the photons.
Computer determines how many
gamma rays from a particular region
and a map is made showing areas of
high to low activity.
PET Versus CAT
CAT scans show brain structures.
PET scans reveal brain activity.
CAT involves absorption of X-rays.
PET involves emission of radiation
by an injected or inhaled isotope.
FUNCTIONAL MRI
Images brain hemodynamics.
Advantages over PET:
– No injections need to be given
– Structure and Function
– Shorter imaging time
– Better spatial resolution
– 3-D images
Check out this website for more info on fMRI
methods: http://www.fmri.org/fmri.htm
Magnetoencephalography (MEG)
MEG measures changes in magnetic fields on the scalp surface that are produced by changes in patterns of neural activity.
Advantage over fMRI– faster temporal resolution
Advantage over EEG– greater accuracy and more reliable localization due to
minimal distortion of the signal
Clinical Uses– Evaluation of epilepsy: to localize the source of epileptiform
brain activity, usually performed with simultaneous EEG
Transcranial Magnetic Stimulation
TMS disrupts neural activity by creating a
magnetic field under a coil positioned near
the skull.
– Disruption of specific cortical locations are
produced while participants engage in cognitive
and/or behavioral tasks.
– This allows researchers to assess functions of
specific cortical areas.
PSYCHOPHYSIOLOGY
Electroencephalography (EEG)
Electromyography (EMG)
Electrooculography (EOG)
Electrodermal activity (Skin Conductance)
Cardiovascular activity – Heart rate (EKG)
– Blood Pressure
– Plethysmography
INVASIVE PHYSIOLOGICAL METHODS IN NONHUMANS
Stereotaxic Surgery
Lesion Methods
Electrical Stimulation
Electrophysiological Recording
LESIONING TECHNIQUES
Aspiration lesions
Radio-frequency lesions
Knife cuts
Cryogenic blockade
Chemical Lesions
NEUROHISTOLOGY TECHNIQUES
Fixation, preservation of tissue,
sectioning and staining of tissue
Uses of histological techniques
– Confirming lesion sites or electrode
locations
– In combination with neural tracing
techniques (anterograde,
retrograde labeling)
– In combination with
autoradiography or
immunohistochemistry techniques
NEUROHISTOLOGICAL STAINING TECHNIQUES
Nissl Stains – e.g., cresyl violet
– stains mainly cell bodies
Golgi Silver Stain– stains whole neurons
Myelin Stains (Fiber stains)– e.g., Weigert stain
– stains mainly myelinFor more information on neurohistological stains, visit:
http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab9/Lab9.htm
Brain images obtained from
http://www.brainmuseum.org
ELECTROPHYSIOLOGY TECHNIQUES
Intracellular unit
recording
Extracellular unit
recording
Multiple-unit recording
– See page 114 in Pinel
NEUROPHARMACOLOGICAL METHODSMeasuring Chemical Activity in the Brain
2-DG Autoradiography– Radioactive 2-deoxyglucose is injected
– Animal engages in behavior of interest
– Animal is euthanized, brain tissue is removed and sliced
– Tissue slices are coated with photographic emulsion and stored in the dark (much like film processing)
– Areas that absorbed high levels of radioactive substance will appear darker
– Using computer imaging, differences in density can be color coded.
e.g., see page 115 in Pinel
Cerebral Dialysis (in vivo microdialysis)
– Under anesthesia and stereotaxic guidance, a cannula is
inserted into a specific brain site.
– Following recovery, a small probe with a semipermeable
membrane is inserted into the cannula.
– Fluid is perfused through the probe and chemicals in the
extracellular fluid diffuse across the membrane and are
collected into a sample vial.
– The samples are then analyzed using a chromatography
methods. (e.g. HPLC)
NEUROPHARMACOLOGICAL METHODS
NEUROPHARMACOLOGICAL METHODSLocalizing Neurotransmitters and Receptors
Immunocytochemistry
– Makes use of antibodies for specific proteins, such as receptors or enzymes.
– The antibody is labeled with a fluorescent die or a radioactive element (commercially available).
– Brain tissue is sliced and exposed to a solution containing the labeled antibody.
– Brain slices are viewed under microscope to identify the regions where protein of interest is distributed.
In situ hybridization
– Also used to locate peptides or proteins in tissue
– Hybrid strands of mRNA are artificially created and labeled with a dye or radioactive element
– Brain tissue slices are exposed to solution containing the labeled mRNA
– Brain slices are viewed under microscope to identify regions where the mRNA expression is highest
e.g., see page 117 in Pinel
GENETIC ENGINEERING
Gene Knockout Techniques
– Creating organisms lacking certain genes
– Limitations regarding interpretation of knockout effects
Most behavioral traits are influenced by the activities of multiple genes
Elimination of a gene may modify the expression of other genes
– Effects of gene knockout may be masked by compensatory changes to other genes
Experience influences gene expression, so effects of knockout may interact with experience in complex ways
Gene Replacement Techniques
– Creating transgenic organisms
e.g. inserting human genetic material into mice
ANIMAL BEHAVIOR PARADIGMS
Species-common behaviors
– Aggressive Behaviors
– Defensive Behaviors (e.g., anxiety paradigms)
– Reproductive Behaviors
– Locomotor Activity
Traditional Conditioning Paradigms
– Pavlovian (Classical) Conditioning
– Operant Conditioning
ANIMAL BEHAVIOR PARADIGMS
Common Learning Paradigms
– Conditioned Taste Aversion
– Conditioned Escape/Avoidance
– Conditioned Place Preference
– Radial Arm Maze
– Morris Water Maze