1. CHAPTER 4 (YES, WE SKIPPED- WE WILL BE BACK!) Methods in Neuroscience

2. 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

3. 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

4. Methods of Research Rules for conducting research  Scientific  Ethical  Many techniques Two main methods:  correlational  experimental method  sub-areas of these, as well

5. 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

6. 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

7. Examples of correlations

8. Experimental Method Allows us to conclude causation Uses general experimental method  hypothesis to test  uses INDEPENDENT and DEPENDENT variables

9. 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

10. Types of Groups of IV Experimental group: gets the treatment Control group:  does not get the “treatment”, but otherwise equal to the experimental group Placebo Group:  a control group  “thinks” they got the treatment

11. 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?

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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