Exam 3 research methods

Different Methods

Connectional methods- function of a neuron depends on its input and output, tracing these connections can tell neuroscientists what the cell does

Correlational methods- observe brain activity while subject performs a particular behavior, observing how brain activity changes as behavior changes provides information about brain regions that are important for that behavior

Causal methods- systematically changing the brain in order to test the resulting change in function

Levels of analysis

Social level

Organ level

Neural system levels

Brain region level

Circuit level

Cellular level

Synaptic level

Molecular level

Reductionism: idea that mind is reducible to brain activity, brain reduced to circuits, then reduced to cellular, molecular, atomic

Techniques

Invasive- technique requires you to enters the body, greater precision, limited to animal models or medical need

Noninvasive- technique does not enter the body, ideal for routine human research, less side effects

In vivo- performing experiment in an intact, living organism

In vitro- experiment on cultured cells or isolated molecules of DNA, RNA, protein

Ex vivo- section of living organism is taken

Brain imaging

Structural imaging- looking at fixed anatomy of brain/cells

Functional imaging- looking at dynamics of the brain in action

Types of resolution

Spatial resolution- how precisely can you measure something in space, distinguish 2 points from each other

Temporal resolution- how precisely can you measures something in time, distinguish events happening in time

Histology

The study of the structure of tissue

Nissl stain- stain that outlines all cell bodies, dyes attach to RNA which is centered on nucleus

Golgi stain- only a small set of cells are stained but the full cell is outlined

Tracer

Chemical that emits light so that you can take a picture and see it

Tract tracers- while animal is still alive, give part of brain “tracer” and then it will transported between neurons

Genetic engineering

Viral infection- viruses highjack the protein creating system of the cell, rabies and herpes viruses modified to express certain proteins of interest, can be designed to target specific neurons

Gene editing-CRISPR-Cas9 technique to insert DNA into DNA sequence, add or subtract some part of animal’s DNA and let them grow up

Brainbow- insert genes that make neurons express many different fluorescent proteins

Tract tracer and gene editing

Target specific neurons with a “viral vector”, change that neuron’s protein expression to create tracer

Tracer spreads to its connected neurons, also make this forward (antegrade trace), across post-synapse or backward (retrograde trace) across pre-synapse

Figure out what types of neurons are connected to each other

2 different colors with 2 different traces see where 2 colors co-expressed

Red+green=yellow

Imaging proteins in neurons

Autoradiography- technique to image spread of drug through brain, put a radioactive tracer on drug, sacrifice and look at which neurons are emitting radiation those are the neurons that got the drug

Immunohistochemistry- create an antibody that targets a particular protein. Inject into brain, sacrifice, look at what neurons show antibody

In situ hybridization- radioactive labeled RNA will bind to RNA that is produced by the neuron that is produced by the neuron, then you see where this gene is being expressed

X-ray based imaging techniques

Contrast x-rays- inject radio-opaque material into structure of interest

Computed tomography (CT) - 3-dimensional, but not high resolution, identify brain bleeding, tumors, traumatic injury

Magnetic resonance imaging (MRI)

Utilizes hydrogen atom -human body has a lot

Magnet strengths measured in teslas 1.5, 3.0, 4.0, 7.0 3T=3 Tesla

Voxel-based morphometry (VBM)- higher resolution than CT, maps shape and thickness of brain regions, measures waves emitted by hydrogen atoms

Diffusion tensor imaging (DTI)- images axonal tracts, identifies connections between different regions, based on rapid diffusion of water molecules

Functional magnetic resonance imaging (fMRI) maps blood flow and oxygenation (blood-oxygen level dependent; BOLD signals) to identify parts of brain active during particular tasks, too slow to catch some neural activity

Positron emission topography (PET)

Radioactivity-based techniques: tag a molecule with a radioactive tracer, intravenous injection while in scanner, radioactive tracer enters brain and processed by certain neurons, tracer undergoes radioactive decay where position released and annihilated with electron, measure the gamma rays at a detector and localize when in brain they originated

Tag specific molecules such as beta amyloid plaques in Alzheimer’s disease and dopamine production in striatum with substance use disorder

Electrophysiology

Recording electrical activity in neurons and brains

Patch clamp- suction cup to one neuron and record electricity

Microelectrode(array) -one or many electrical recording sensory, population of neurons

Electocorticography(ECoG) - sensors placed directly on or in the brain, specific area of brain

Electroencephalography (EEG) - sensors placed on scalp, limited spatial resolution, event-related potentials (ERPS) , sensory invoked potentials, signal averaging

Intracellular unit recording- records the membrane potential of neuron as it fires

Multiple-unit recording- record action potentials of many nearby neurons

Extracellular unit recording- records the electrical disturbance that is created each time an adjacent neuron fires

Invasive EEG recording- large implanted electrode picks up general changes in electrical brain activity

Magnetoencephalography (MEG) measures magnetic fields in brain instead of electricity

Why study humans

1. Higher-order cognition: language, decision-making, emotion/ social processes

2. Different brains might be different across species

3. Measure the whole brain with MRI/EEG, might miss something if focused on region

Experimental design

Variable-some measurement we’re making

Correlation - looking for relationship between 2 things

Confounding variable- third variable that is better explanation for relationship

Contrast- subtracting one condition from another to isolate a single variable

Experiment - administering an intervention that changes something

Independent variable- the variable that experimenter changes to see what happens

Dependent variable-measure what happens when you changed something

Controlled setting- limited amount of confounding variables

Control group- another group that receives a placebo or fake intervention just to make totally sure experiment itself doesn’t change dependent variable

Blinding- intentionally design experiment so participants don’t know what group they’re in

Double-blinding- make sure experimenters don’t know either

Blinded analysis- analyst doesn’t know what group was which till end

Placebo effect- think they have the treatment, drugs need to outperform placebo effect to be effective

Nocebo effect- make yourself worse

Between-participants- one group gets real intervention and other gets fake intervention (aka parallel arms)

Within-participant-each persons gets real and fake intervention (crossover study)

Randomized clinical trial- intervention in which participants are randomized into one arm

Screening- recruit participants see if eligible

Enrollment- participants sign informed consent

Randomized- randomly assigned

Preregistration- write down predictions

Somatic intervention- change their body see if behavior changes

Behavior intervention- change behavior see if body changes

Correlation to causation

1. Identity correlation between 2 variables

2. Design experiment to see if there’s a causal relationship between variables by delivering intervention to change one of them

3. Check that intervention engaged the target

4. See if dependent variable changed as a result

5. Process builds causal evidence

Lesions

Areas of brain damaged by disease and injury

Ablation studies- destroy part of brain that’s was found to be important for particular behavior

Muscimol inactivation- inject compound into region of brain and shut it down temporarily

Stereotactic surgery- employs stereotactic atlas and instrument, allows accurate placement of lesions, probes, electrodes, and other instruments, reference point is bregma

Gene techniques

Gene knockout- remove particular gene from genetic code and grow up without gene

Wild-types control group that have no genetic manipulation

Gene knock-in : transgenic mice, genetic information from different species implanted

Gene editing: CRISPR/Cas9

Brain stimulation

Electrical stimulation- stimulate electrically at different levels

Transcranial electrical stimulation- noninvasive stimulation through pads on scalp

Deep brain stimulation- implanted electrodes

Electrical micro stimulation- stimulation at microscopic level of populations of neurons

Transcranial magnetic stimulation (TMS) uses electromagnetic coils to activate neurons in particular region of brain

Transcranial focused ultrasound stimulation delivers mechanical vibrations to brain and activates the targeted area, sound waves measure changes in blood volume

Optogenetics

Insert light-sensitive ion channels into neurons, then shine laser on ion channels to open them, one ion channel activates cell and another inhibits the cell

Behavioral paradigms

Paradigms for assessment of species-common behaviors: open field test, tests of aggressive and defensive behaviors, tests of sexual behaviors

Traditional conditioning paradigms- Pavlovian conditioning

Radial arm maze, morris water maze- study rat spatial ability

Neuropsych assessments- intelligence, memory, language tests

Biases

Anchoring bias- tendency to be overly influenced by single observation, typically first observation

Confirmation bias- tendency to seek out and emphasize information matching existing beliefs

Critical thinking

Scientific method provides systematic way to study a process and avoid biases and heuristics

Make observations about world

Develop hypothesis

Generate testable predictions

Perform experiments

Payoffs of cognitive neuroscience

Healing disordered brain- rTMS and deep brain stimulation help depression, Parkinson’s, OCD

Enhancing human abilities- understand how humans make decisions and how to make better ones, brain interface devices can restore lost functions to individuals

Blueprints for artificial cognition- improve abilities of technology

Brain-compatible social policies- cognitive neuroscience help understand and explain factors influencing memory of eyewitnesses, medical practices