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What are the two main types of techniques used to study the brain?
Manipulation techniques and measurement techniques
Manipulation Techniques
A technique that alters the structure or function of the brain; the resulting effects are observed
Measurement Techniques
Brain activity is measured during a task with an aim to identify the brain areas involved in performing that task
What are some brain manipulation techniques?
Lesions, brain stimulation (DBS and TMS), optogenetics
Lesions
Destroy a part of the brain; assumes that the function of a specific brain area is the behaviors lost after damaging that part of the brain area
What do you need to make a causal claim?
You need a proper control group
Sham-lesions
"Placebo" procedure that replicates the lesion preparation process, but without taking out the lesion so this make include anesthesia and surgery
What are the issues of lesions?
-No control group for humans; only for animals (sham lesions) -Diffused damage; not localized (hits a bunch of brain regions, not sure what causes what) -Cortical reorganization; Brain can reorganize to account for damage -Hard to know if behavior was even localized
Deep Brain Stimulation (DBS)
Electrodes implanted into a brain region and emits pulses of electrical current; used to treat Parkinson's and Obsessive-Compulsive Disorder
What are the problems with DBS?
Surgery Risks (very invasive); incorrect placement of this can cause potential harm
Transcranial Magnetic Stimulation (TMS)
A noninvasive technique that sends magnetic pulse through the cranium that depolarizes the cortical cells; useful for depression
What are the problems with TMS?
-Localizing issues and difficult to make interpretations -Reproducibility issues -Safety issues if used by a non-expert
Optogenetics
Technique that uses genetic engineering to express membrane channels to be light sensitive; insert proteins into particular areas and apply light; great to understand neural circuity
What are the problems with Optogenetics?
-Identify how cells respond with the light stimulation, but not how the cells respond normally -Want to be more precise with neuron subtypes -Only on animal scale level
What are some measurement techniques?
-Electrical activity (single/multicellular recordings, EEG/ERP, MEG) -Functional Brain Imaging (fMRI and PET) -Structural Methods (CT and MRI)
Cellular Recordings Types
-Intracellular recordings places electrodes directly into a neuron -Extracellular recording places electrodes in fluids surrounding the neurons to record electrical activity -Single Cellular uses one electrode; multicellular uses multiple (typically in extracellular)
EEG
-Put electrodes on scalp to measure "brain waves" -Average out summed graded potential of many neurons to cancel out noise -Sometimes has rhythmic waves
ERP (Event Related Potential)
-Uses EEG and synchronizes it with a task -has great temporal resolution -bad spatial resolution! -Need to show same stimulus a lot and average out trials to get a distinct wave -Can have positive and negative waves
What does P300 mean in ERP?
Positive Wave 300 ms
What are the problems with ERP?
-Difficult to figure out where the electrical signals originate from -Skull distorts signals
electrocorticography (ECoG)
-Intercranial EEG -Usually paired with a form of stimulation
MEG
-Uses magnetic waves so waves not distorted by skull -Better spatial resolution than EEG -super duper mega expensive because you need mega strong magnet + bunker to shield out earth's magnetic field
PET
-Uses a radioactive tracer injected into the bloodstream and tracer binds to something -Used with biomarkers of disorders and pathologies -Has a lack of structure with its imaging -Helpful for task related activation and metabolism/neurochemistry
What are the cons of PET imaging?
-Lower spatial resolution -Slower temporal resolution -Doesn't image brain structure -Uses radioactive substances
MRI
-Amazing spatial resolution; shows brain structure (white/gray matter, CSF, bone) -Uses extremely strong magnets -Noninvasive -invented at washu lol
fMRI
BOLD
Blood Oxygenation Level Dependent
What are the traits of a oxy-hemoglobin?
-Diamagnetic (repelled by magnet), normal BOLD signal
What are the traits of a deoxy-hemoglobin?
-Paramagnetic (attracted to magnet), low BOLD signal
What cause higher BOLD signals?
A surplus of oxygenated blood; this can be a result of brain needing more oxygen so there's increased blood flow to brain with blood that has oxygen
What causes the initial dip in the BOLD graph of fMRI?
This is when a neuron consumes oxygen and that causes us to have more deoxygenated hemoglobin than oxygenated hemoglobin causing the BOLD signal to decrease.
What causes the overshoot of the BOLD graph?
In response to the undershoot, there is increased bloodflow to that region of the brain which drastically increasing the BOLD signal.
What causes the undershoot of the BOLD graph?
Relaxation of the venous system
Voxel
3D Pixel
How do we get from BOLD graph to imaging?
-We average out voxels of a region to get a color -Map that onto the brain
Pros of fMRI
-Fine spatial resolution -Fine temporal resolution -Noninvasive
Problems of fMRI
-Indirect measure of neural activity -temporal and spatial res have their limits -Activated areas may be associated but not necessary for tasks
Structural Methods
Method focuses more on taking snapshots rather linking to behavior due to behaviors being more dynamic; often combined with another method
Computerized Tomography
-3D X-ray -Cheap and fast -Bad spatial resolution but identifies major structural problems; shows bone better than MRI -Used when magnets cannot
Problems of MRI
-Movement matters (have to stay still!) -Expensive -Statistical issues
What are the traits of a deoxy-hemoglobin?
-Paramagnetic (attracted to magnet), low BOLD signal
Psychopharmocology
The study of drugs that affect the nervous system and behavior
Drug
Exogenous chemical not needed for normal cellular functioning and it significantly alters functions of the cells in the body when taken at low doses
Are neurotransmitters drugs?
No, they are endogenous and produced by us naturally
How does drugs affect people?
-They can change physiological processes and behaviors -They have sites of actions in which they can bind onto the cells of the body and affect the biochemical processes
Pharmacokinetics
What the body does with the drug; movement of the drug ex. Absorption, Distribution, Metabolism, Excretion
Pharmacodynamics
What the drug does to the body ex. Action mechanisms, adverse effects
Absorption
How we administer the drug into our body; first step of pharmacokinetics ex. oral, IV injection, inhalation
Routes of Administration
Ways to insert drug into body/Absorption
Cyclobenzaprine
A drug that is a muscle relaxant
Distribution
Where the drug goes after it's absorbed in us; second step of pharmacokinetics
Blood-Brain Barrier
-Barrier that restricts the indiscriminate access of certain substances in the bloodstream to CNS -layers of cells that prevents substances in the circulating blood from freely entering the extracellular fluid of the brain
What is the blood-brain barrier made of?
Astrocytes
What part of our body receives most of the drug?
Liver, kidney, and other well-irrigated organs
How is the drug distribution towards muscles, most viscera, and adipose (fatty) tissues?
It is slower because they are less well-irrigated
Placental Transfer of Drugs
Some drugs can make it through while some cannot
What parts of us do we lack Blood Brain Barrier in?
-Pituitary Gland -Pineal Gland (day/night cycle) -Area Postrema (vomit toxic substances)
Metabolism
Set of reactions and transformations that drug undergoes in the body; third step of pharmacokinetics
Oral Intake of Drug Pathway
Goes to our stomach -> Small Intestine -> Gut Wall -> Liver -> Brain
Excretion
Elimination by body of residues of drug metabolism; last step of Pharmacokinetics
What body part is most important for excretion?
KIDNEY!!
Name some of the excretion pathways
Renal (kidney), Breastmilk, Biliary (bile) and fecal, sweat saliva tears, and pulmonary (lungs)
What happens if we keep taking very high doses of a drug?
At a certain dose, the effect of the drug starts to level off where having higher doses of a drug does not increase the effect of the drug.
Margin of Safety
A dosage range where the drug is still effective while minimizing the side effects/negative effects of the drug
Tolerance
Decrease in effectiveness of a drug that has been administered repeatedly -decrease in effectiveness of binding -less sensitive receptor or number of receptors decreases -coupling less effective
Withdrawal Symptoms
Symptoms that occur after chronic use of a drug is reduced or stopped
Sensitization
Increase in effectiveness of a drug that is administered repeatedly -less common than tolerance
Can you get both sensitization and tolerance?
Yes! ex. repeated use of cocaine increases the effects of the jerkiness/movement disorder but euphoric effect might even show some tolerance
Agonists
A drug that mimics or facilitates the effects of a neurotransmitter on the postsynaptic; helps the system and the NT's goal ex. precursors
Antagonists
A drug that opposes or inhibits the effects of a neurotransmitter on the postsynaptic cell; hurt's the NT's goal ex. prevent synthesis of the NT
Direct Agonist
A drug that binds with and activates a receptor; membrane channel opens -competitive
Direct Antagonist
A drug that binds with a receptor but does not activate it; prevents the natural NT from binding to the receptor and does not open the membrane channel -competitive
Indirect Agonist
a drug that binds to a different site from the NT but facilitates the NT's function -noncompetitive
Indirect Antagonist
a drug that binds to a different site from the NT but inhibits the NT's function -noncompetitive
How many types of psychotropic medications are there?
5 types:
Antidepressants
Mood stabilizers
Anti-anxiety medications
Stimulants
Anti-psychotics *drug that falls into these categorically aren't necessarily used to treat those specific disorders
Antidepressants
Used to lift mood out of a depressive episode -many are reuptake inhibitors ex. SSRI, SNRIs, etc. -MAOI (MAO Inhibitor) - MAO typically breaks down some of the NTs so MAOI serves to prevent MAO from functioning to allow the NT last longer -Tricyclics
What do antidepressants treat?
Depression... anxiety, phobias, PTSD, etc.
Manic Episode
mood disorder where mood is abnormally high
Depression
your low point
Hypomania
elevated mood but not as high as an manic episode
What does dopamine do?
involved with movement, pleasure, reward, and more
What is norepinephrine involved with?
regulates mood, wakefulness, cognition, and other functions
What is epinephrine involved with?
regulates mood, anxiety, sleep, and other
Reduced Positive Affect
Going from high to low; lots of interest/pleasures, loss of energy/enthusiasm -DA and NE dysfunction
Increased Negative Affect
Lows become even lower -ex. negative feelings become worse; more disgust, more guilt and anxiety -5HT and NE dysfunction
Mood Stabilizers
-Stabilizes mood -REGULATES mood so it doesn't get too low or too high (prevents depression or mania) -ex. Lithium, anticonvulsants
Mood Disorder
all forms of depression and bipolar disorder
Anti-Anxiety Medication
-AKA Anxiolytic -types of medication include: SSRIs and SNRI (anti-depressant too!) -Anticonvulsants -Benzodiazepenes
How much overlap does depression and anxiety have?
A LOTTT!! They also have genetic overlap
Benzodiazepene
-Depressants/sedatives; feeling of calmness, drowsiness -GABA agonists (GABA is inhibitory) -inhibits arousal system -lots of potential for withdrawal system and dependence -ex. Xanax
Should you take alcohol and benzodiazepene together?
Alcohol is also a GABA agonist by maximizing time that GABA channel stayas open. Benzodiazepene increases frequency that GABA channels stay open. These summed effects can have detrimental effects such as depressing your respiratory system
Stimulants
-drugs that bring you up as opposed to anxiolytics bringing you down ex. Amphetamines (Adderral and Ritalin)
Why is taking adderall (a stimulant) and alcohol potentially bad for you?
Adderall is a stimulant which gets cancels by the effects of alcohol which is a depressant. This causes people to intake more alcohol to feels the effect of the alcohol which can lead to alcohol poisoning
Anti-Psychotics
-AKA Neuroleptics -Two types: Typical and Atypical
Psychosis
Condition where people lose touch with reality; hard to tell what's real and what's not real
Typical Antipsychotics
Drug that blocks dopamine at the D2 Receptor; tight binding (really blocking); high risks of side effects
Atypical Antipsychotics
Drug that blocks dopamine at D2 Receptor loosely; less risks of side effects compared to its counterpart, useful!
Order of Operations
Antipsychotic related issue
Substance Abuse
Mood Disorders
Anxiety Disorders
ADHD Treatment
Nicotine Dependence
TRUE OR FALSE: Not all drugs lead to substance abuse disorder
FALSE!!! Any drugs can lead to a substance abuse disorder
Substance Use Disorder
Complex Brain Disorder characterized by: -Compulsion to seek and take drug -Impaired control in limiting drug -Progressive neglect of alternative pleasures or interests -Persistent to take the drug despite the consequences -Relapse
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