CHAPTER 4 (YES, WE SKIPPED- WE WILL BE BACK!)

Methods in Neuroscience

Research, Theory and Science

Relies on EMPIRICAL DATA as its means of acquiring knowledge

Relies on SCIENTIFIC METHOD hypothesis testing and theories operational definitions systematic observations

Common sense and folklore may or may not be “true”

Science differs from folklore and tradition because it uses empirical method

Science (and thus neuroscience) is Tentative

Conclusions based on current information New information always being acquired This creates a problem: what was true yesterday is probably not

true today, and what is true today is probably not true tomorrow!

Science is evolving, rapidly changing, and ambiguous

Relies on theories: Integrative interpretation of diverse observations Attempt to explain some phenomenon Based on evidence Conclusions pulled together logically Explains current facts Suggests new hypotheses and experiments to constantly test

and refine the theory

Methods of Research

Rules for conducting research Scientific Ethical Many techniques

Two main methods: correlational experimental method sub-areas of these, as well

Correlational method

NON experimental

looking at relation between two variables effect of X on Y

Correlation DOES NOT IMPLY CAUSATION

values of -1.0 to 0 to +1.0 closer to 1.0 is stronger relationship if value is close to 0, little relationship

Two types of correlations

Positive correlation: 0 to 1.0 as X goes up so does Y rate of waterskiing and outside temperature

Negative correlation: 0 to -1.0 as X goes up, Y goes down rate of hot chocolate intake and outside temperature

Examples of correlations

Experimental Method

Allows us to conclude causation

Uses general experimental method hypothesis to test uses INDEPENDENT and DEPENDENT variables

Conducting an Experiment

Need independent and dependent variables Variable = any characteristic or condition which is

subject to change Independent variable: what the experimenter

manipulates or changes Dependent variable: what the experimenter measures,

what was changed by the I.V. Experimenter manipulates IV, measures DV

WAY that the IV is manipulated is important: assumes using a random sample control for extraneous (extra or outside) variables use systematic observations

Types of Groups of IV

Experimental group: gets the treatmentControl group:

does not get the “treatment”, but otherwise equal to the experimental group

Placebo Group: a control group “thinks” they got the treatment

Many Research Techniques in Neuroscience

Which are correlational? No random assignment to groups Linking or relating A to B

Which are causal? Random assignment Researcher manipulates independent variable

Does it make a difference?

Techniques include

Cell work: study brain cells or slices

Measuring brain activity in live organisms: Scans of functioning brains Implanting measurement tools and measuring

Animal models

Post-mortem examination

Research techniques in neuroscience:Staining and imaging neurons

Golgi stain method: randomly stains about 5%

of neurons in slice Places them in relief

against background Can see patterns

Myelin stains: Stain taken up by fatty

myelin that insulates axon Stain helps identify neural

pathways

Nissl stains: Stain taken up by

neurons Identify cell bodies of

neurons

Research techniques in neuroscience:Staining and imaging neurons

Autoradiography Use fluorescent dye:

flurogold Make neurons stand out Importantly: tells which

neurons are active Can correlate with

behavior

Also use radioactive tracers: 2-DG (2-deoxyglucose) Make this sugar

radioactive Is taken up by neuron Can trace where it went

Can also stain for neurotransmitters or other brain chemicals

Light and Electron Microscopy

Electron microscope: Passes beam of electrons through

thin slice of brain tissue onto photo plate

Different parts of tissue block or pass electrons at different degrees

Electrons produce image based on this variance

Scanning electron microscope: Beam of electrons causes specimen

to emit electrons itself These are captured by photo plate Not as great of magnification, but

image is 3-D

Measuring Brain Activity

Electroencephalography or EEG Hans Berger, 1929 Recorded from two electrodes on

scalp over area of interest Electronic amplifier detects

combined electrical activity of all neurons between these two neurons

Can graph activity Terrific temporal resolution: 1

millisecond recording Spatial resolution is poor

Why use? Detecting changes in brain patterns

or arousal Can average several readings to

obtain evoked potential Signal – background noise Gives better estimation of patterns

Often used for detecting epilepsy and other brain disorders, sleep disorders

Stereotaxic techniques:

Stereotaxic device: Allows precise

positioning in brain of electrode or other device

Holds head in position 3-D: height x depth x

width Use stereotaxic atlas to

find locations Brain atlas!

Several kinds of things might be put into brain Cannula Electrode

Stereotaxic techniques:

Allows one to ablate or lesion precise areas of brain Alter specific area to

determine function Examine pathways

Several kinds of measures Electrophysiology Electrodialysis Fast scan cyclic

voltammetry

All allow measurement of brain electrical and chemical changes

Brain Imaging

CT or CAT scan: Computed tomography X ray scanning Produces series of x

rays taken from different angles

Combined using computer to create series of 2-d horizontal cross sessions or slices

Presented as series to make 3-D

Brain Scanning: MRI

Magnetic Resonance Imaging or MRI Measures radio-

frequency waves emitted by hydrogen atoms when they are subjected to strong magnetic field

Extremely fast Can scan very small

areas clearly

Brain Scanning: PET

PET: positron emission tomography Involves injecting radioactive

substance into bloodstream Is taken up by parts of brain

according to how active each area is

Often radioactive 2-DG Use other radioactive tracers

to mark bloodflow, oxygen uptake

Requires lots of training and access to cyclotron Cyclotron supplies radioactive

substances

Provides estimates of brain activity and changes in brain activity

Brain Scanning: fMRI

fMRI: functional magnetic resonance imaging

Measures brain activation by detecting increase in oxygen levels in active neural structures

Can be used as individual is engaging in a behavior or cognitive task

Can see changes as behavior changes Important: don’t have to

ablate or lesion to determine function

Allows use of human subjects

Studying heritability and genetics

Family studies: Determine how strongly a

characteristic is shared across family members

Quantify Correlate degree of heritability

Adoption studies Compare adopted and biological

children Compare behavior in adoptive vs

biological family

Twin studies Identical vs. fraternal twins

Concordance rate: frequency with which relatives are alike in characteristics

Genetic Engineering

Genetic engineering: Manipulation of organism’s

genes or their functioning

Knockout technique: Nonfunctioning mutation is

introduced into isolated gene

Altered gene is transferred into embryo

Antisense RNA procedure: Blocks participation of

messenger RNA in protein construction

Genetic Engineering

Gene Transfer: Gene is inserted into an

animal’s cells

Transgenic animal: Gene is inserted into

animal embryo Embryo now has that

trait

Genetic Engineering Manipulate genes to turn

on/off different traits Goal is to be of

therapeutic use

Research Ethics

Regulatory Animal research:

IACUC: Institutional animal care and use committee 5 federal agencies have federal guidelines

NIH human subjects use

Problems: Plagiarism Fabrication of data

Ethical dilemmas Gene therapy Stem cell therapy