FINAL EXAM

maximising

choosing alternative with highest expected value

• brain wants to maximise ventral striatum and medial frontal cortex activation

  • VS: codes for expected value of upcoming reward, if it fires more you feel pleasure

  • fMRI: neurons fire in caudate, nAcc, putamen (ventral striatum) in expecting reward

expected value

reflected in ventral striatum

• bulimic higher activity in VS for food

• addicts higher nAcc activity for drugs

neural predictors of purchases

preference and price weighed —> price differential

• preference pathway: more preferred products → more striatum activity → higher EV → more often purchased

high striatum activity predicts purchase

costs in the brain

ACC

insula: processes negative bodily feedback, creates disgust

• pain of price: purchased somtihing —> lower insula activity

cost and value integration, making a choice

vmPFC integrates gains and losses

gains: striatum (nAcc)

losses: ACC, insula

choice:

• mPFC activity when item is most preffered

• striatum activity when most preferred

  • mPFC and nAcc track subjective value

brain scan predicting relapse

addict brains:

• mPFC: drugs more activity than food or neutral

• nAcc: drugs same as food (normal: the same)

nAcc responses to cues response relapse

• most response —> soonest relapse

predicting behaviour change

self-reports not significant

mPFC activity is significant

• predicts persuasiveness of advertisements

  • represents recipient resonation

neuroforecasting

neural effect measurements of a small group likely has similar effects on population level

• individual preferences scale to the population level

• mPFC activity is better than effectivity ranking

auditory analysis of sound

• pattern recognition

• comparison to templates: auditory cortex

• entrainment (MNS)

• prediction of ensuing music

• prediction of reward/how nice the next music is

  • assessment of those predictions with reality → contribute to emotional experience (amygdla) 

music and language similarities

sound patterns that unfold over time

• have melody and rhythm

• 250-500 ms time to decide if music is familiar/emotional

• decoded by brain to get meaning

• music: can happen with multiple people participating at once, language only makes sense one at a time

mechanisms sound —> meaning

hardwired responses, extramusical associations, anticipation

BRECVEMA

• brain stem reflex

• rhythmic entrainment

• evaluative conditioning

• contagion (emotion)

• visual imagery

• episodic memory

• musical expectance

• aesthetic judgement

lower=more complex and individual

brain stem reflex music types

• sad music → decreased heart rate and skin conductance, higher blood pressure

• scary music: increased pulse, decreased pulse amplitude

• happy music → decrease depth of respiration

• hippocampal activity: associated w/ music-evoked emotion

auditory processing stream organisation

dorsal: spatial processing, tracks time-varying events

ventral: time-independent sound properties

• melody and lyrics are processed separately

• hierarchical (simple/complex

• hemispheric (left:spectral, right:sequencing)

• dorsal/ventral (where/what)

auditory processing streams

pitch processing

STC (superior temporal cortex), A1, A2: processes pitch, loudness, tonal relationships + templates

• different aspects of a tune are processed in different streams

• melodies engage neurons in anterior and posterior pathways

rhythmic entrainment

motor regions: interact to percept and product rhythm

premotor regions: track rhythms spontaneously

cortico-cerebellar circuits: subserve differential aspects of rhythmic synchronisation

• cerebellar deficit → fast rhythm tracking impaired

• rhythm and pitch are separate, but interact

• auditory-motor co-activity when sound/movement is congruent

musical expectancy

• anticipation depends on the organisation of sounds into a meaningful succession of events (predictive coding)

• constant prediction means that music listening is active listening

• predictions depend on 

  • learning, familiarity with genre, short-term memory

• music has many layers to predict → prediction will be right in one part (minimal prediction error)

PCM

predictive coding model: music perception is a bayesion process

• goal : minimise prediction error

• aspects of music experienceweighed to predict, weights are constantly updated

uncertainty and pleasure scanning (music)

predictable music: unpredictable parts are pleasurable and vice versa

• amygdala, hippocampus, auditory cortex: reflects pleasure and surprise/uncertainty

• nAcc: predicts the outcomes and reflects amount of uncertainty only

• caudate: firing in anticipation (decides number of chills)

• nAcc: firing in anticipation payoof (amount of chilsl)

social brain and music

1. superficial amygdala: processes stimuli with socio-affective significance (like music)

2. music-evoked pleasure: activity of the dopaminergic mesolimbic reward pathway

3. hippocampal formation : emotion related to social attachments

drug

chemical substance of known structure which produced a biological effect when administered

• synthetic chemical, chemical obtained from plants, biotechnology products

toxicology

study of toxic effects of chemical substances

pharmacology

study of the effects of drugs

pharmacokinetics

what de body does to a drug

pharmacodynamics

what a drug does to the body

drug disposition

ADME: absorbtion, distribution, metabolism, elimination

• speed of onset

• intensity of effect

• duration of action

pharmacokinetic parameters

aspects of the drug that help decide

• route of administration

• amount and frequency of dose

• duration of treatment

ro

routes of administration

enteral, parenteral

enteral administration

by mouth (safest and most convenient

1. swallowed —> oral delivery

   1. enteric-coated preparations: chemical envelope resisting stomach enzymes, opening in upper intestine

   2. extended-rekease preparations: special coatings control how fast the drug is released from teh pill

2. sublingual: under the tongue —> direct bloodstream absorbtion

parenteral administation

any route that doesnt absorb in GI tract (IV, intramuscular, subcutaneous and transdermal routes)

• most control over the dose

• irreversable, pain, local tissue damage

• oral and nasal inhalation —> across mucous membranes

• intrathecal/ventricular —> into CSF

• topical application: local effect of drug

• transdermal: to skin

• rectal (no liver effect to the drug)

drug absorbtion

passage of a drug from administration site into plasma

• moving across cell barriers/membranes

• passive diffusion, facilitated diffusion, active transport, endocytosis (into vesicles)

membrane permeation / factors affecting absorbtion

• pH

  • drug can only pass through membranes if uncharged

  • acidic drugs: release proton and form charged anion (AH ←→ A- + H+)

  • weak bases: lose proton —> uncharged (BH+ ←-> B + H+)

  • distribution b/w ionised and non-ionised forms depends on pH and pK of the drug (decides absorbtion rates

• bloodflow to absorbtion site

• total absorbtion area

• contact time at surface

• expression of P-glycoprotein (transmembrane transporter

bioavailability

fraction of drug that reaches systemic circulation

• need to calculate dosage

• route and chemical physical properties affect this

factors affecting bioavailability

fist-pass hepatic metabolism: how much goes to the site of effect before being exposed to the liver and being metabolised

solubility of drug

chemical instability

nature of drug formulation

bioequivalence

when 2 related preparations show comparable bioavailability and similar time to peak blood concentrations

drug distribution

process where a drug reversibly leaves bloodstream and enters interstitium (extracellular fluid) and tissue

volume of distribution

how widely the drug is distributed in the body

Vd = amt of drug in body / C0 (plasma concentration at t0)

blood-brain barrier

levodopa crosses BBB through aminoacid transport mechanism —> conversion to active dopamine in basal ganglia

drug half-life

time for the concentration of a drug to reduce by 50%

• large Vd (volume of distribution) —> influences halflife (depende on amt of drug delivered to liver or kidneys at a time

drug elimination

1. hepatic metabolism

2. elimination in bile

3. elimination in urine

• cause exponential decrease of plasma concentration

• clearance: amount of drug cleared from body per unit of time

• CL = 0.693*Vd (volume of distribution) / t1/2 (half-life)

  • pulmonary and hepatic clearance most important

types of drug actions on the body

1. receptors: agonist (stimulates receptor) / antagonist (blocks receptor)

2. ion channels: blockers or modulators of opening probability

3. enzymes: inhibitor, false substrate for breaking down, prodrug (the real drug is produced with the enzyme

4. transporters: inhibitor, false substrate

types of receptors

• ligand-gated ion receptors (milliseconds)

• G-protein coupled receptors (seconds

• kinase-linked receptors (hours)

• nuclear receptors (in nucleus, hours)

affinity: how mucha. drug is attracted to the receptor

signal transductionel

when a drug-receptor complex alters biochemical/molecular activity of a cell

dose-response relationships (potency and efficacy)

increase in drug concentration —> its effect also increases

potency: amount of drug necessary to produce an effect of a given magnitude (potenct: EC50 == 50% of maximum

efficacy: ability of drug to elicit a response when binding to a receptor

• greater efficacy > more potent

  

agonists

full: drug binds to receptor and produces maximal response, mimicking the normal response

partial: less than full response

inverse:binds to receptor as agonist but induces opposite response

antagonist

decrease/oppose the actions of another drug/endogenous ligand (has no effect if the agonist is not present

competitive: if antagonist and agonist bind to same site

irreversible: maximum downwards shift

therapeutic index

ratio of the dose that produces toxicity to the dose/dose that produces a desired effect

TD50: dose that produces toxic effect in half of population

ED50: dose that produces desired response in 50% of population

TI = TD50 / ED50

autonomic nervous system

sympathetic and parasympathetic divisions have antagonistic functions

• sympathetic: arousal, energy

  • parasympathetic: oposite, calming

ACh and noradrenaline

drugs affecting autonomic nervous system

cholinergic: acts on ACh receptors

adrenergic: acts on norepinephrine/epinephrine receptors

cholinergic agonist action sites

muscarinic receptors: PNS ganglia, autonomic effector organs. Ach and muscarine binding (low nicotine)

nicotinic receptors: CNS, adrenal medulla, autonomic ganglia, neuromuscular junction. ACh and nicotine (low muscarine

pilocarpine

cholinergic agonist

• less potent than Ach, but penetrates CNS

• glaucome use

• applied to cornea

• used with atropine to counteract toxicity

major catecholamines

norepinephrine, adrenaline, dopamine, isoprenaline (synthetic norepinephrine)

types of adrenergic receptors

adrenergic agonists

direct-acting: direct of alpha or beta receptors —> stimulates sympathetic nerves

indirect-acting: block norepinephrine uptake

mixed-action agonist

pharmacological effect of epinephrine

1. cardiovascular system (contractility of myocardium, rate of contraction, renin release, dilate vessels, constricts arterioles

2. respiratory ystem: bronchodilation

3. hyperglycemia: decreased insulin, increased glucagon

4. lipolysis

uses: anesthetics, cardiac arrest, anaphylactic shock, bronchospasm

amphetamines

effect: locomotor stimulation, euphoria, insomnia, stamina, anorexia

side effects: anxiety, irritability, paranoia, psychosis

pharmacokintetics: absorbed from GI tract, penetrates BBB, half-life from 5 to 20/30h

parkinson’s medication

levodopa (dopamine prescursor) and carbidope (dopa decarboxylase inhibitor

DA receptors (G-protein-coupled) expressed in CNS and periphery

schizophrenia and drugs

symptoms: delusions, hallucinations

strongly genetic, probably DA pathway disturbance

reduced synaptic nerve ending density

1. 1st gen: competitive inhibitors: bind (block) to DA neuroreceptors

2. 2nd gen: clozazepine: less extrapyramidal symptoms (diskinesia, parkinsonism

harmful effects of drugs

paracetamol: liver cell death resultingfrom its metabolism

thalomide: teratogenesis (structural malformations in fetus)

why merge autism diagnosis? pros cons

+ easier funding, less stigma for more severe patients, more people in GWAS study, easier insurance, uniform diagnosis across countries

- studies might study different groups, high variance of symptoms makes sudying it harder, more stigma for aspergers

autism epidemic

more autism, less intellectual disability

risk factors autism

• autistic family

• cerebellar injury at birth

• romanian orphanage

• >9 weeks premature (skip out on gliogenesis)

• <1 birth interval

• hurrican strike zone

• marent wth mental illness

• father >40

• mother >35

genetics autism

very polygenic

• deletion and duplication de novo

network of genes related to synapse development, axon targeting, neuronal signalling

gender bias autism

• females have stronger average connections with other genes from identified network

• females have a protective effects needs higher genetic differences to trigger ASD phenotype

A: multiple threshold model: higher predispostion needed for females to reach threshold of symptoms

B: multifactorial liability model: female-specific factors shift female’s autism liability distribution away from the universal threshold

neuropathology ASD

amygdala: 13-16% bigger in young children, abnormal growth trajectory in puberty

disorganisation of neocortex in children

cerebellum: smaller, loss of purkinje cells, hypoplasia of vemris

eary autism diagnosis (lecture)

• cognitive and adaptive rates are better when getting intensive behavioural intervention young

• access more intervention, better verbal and overall cognition, more likely to attend mainstream school, required less ongoing support

basis of autism 2 hypotheses

cerebellum and autism

cerebellar damage: ASD symptoms

developmental perturbation → long lasting perseveration and deficits in social preference

acute cerebellar perturbation → increased cerebellar perturbation and decreased cognitive flexibility

ASD in mice

count behaviours in standard and enriched housing

negatives: hard to assess mood changes, tests not specific enough, medication reaction different, cannot use transgenic approach bc of polygenicity.

—> diagnosed autistic mice can then be tested in different circumstances

EEG

• noninvasive

• measure of electrical brain activity for scalp surface

• generalised cortex activity

+ temporal precision, population-level neural activity

• low spatial resolution, inaccurate for asychronous/smallscale actitivty

how does EEG work?

neurons have to be parallel and synchronous

• negative voltage : excitatory synapse at dendrites

interpretation of EEG

• neural oscillations: perceptual, cognitive, motor, emotional processes

  • no real understanding

EEG vs EMG vs fMRI

EEG+EMG better time resolution than fMRI

EEG: clinical research but EMG only research

EEG: cheap, easy to carry and use

EMG: only measure outward direction of magnetic waves

EEG signals

• delta band (0.5/4 Hz)

  • predominant in babies

  • adults: sleep/hypoxia

  • frontal location (temporal and parietal lobe and thalamus)

• theta band (4/8 Hz)

  • drowsy, light sleep

  • memory encoding/retrieval

  • frontal midline theta level correlates with changes in anxiety levels (associated with hippocampal theta rhythms

• alpha band (8-14 Hz)

  • relax state, eyes closed

  • control inhibition

  • parieto-occipital brain areas

    • thalamus, pulvinar, lateral geniculate nucleus

• beta band (14/30 Hz)

  • cognitive processing and motor control

  • frontal and central brain areas

  • parietal and temporal lobes

• gamma band (>30 Hz)

  • sensory information, retrieval, episodic memory

  • hippocampus, sensory areas

  • premotor, parietal, temporal, frontal regions

ERP

event-related potential

• transient-average fluctuation in the brain-s field as response to stimulus

• probably reflects sum of postsynaptic potentials of synchronously active pyramidal neurons or cerebral cortex

mismatch negativity

diff b/w frequent stimulus and presentation of an oddball

100-250 ms

ERP’s: N400, P1-50, N1-100, P300

N400: semantic incongruence (negative 400)

P1-50: sensory gating (positive 1-50)

N1-100: change in auditory stimulus (can be positive or negative)

P300/P3: elicited by oddball experiment

selective attention

ERP shows that selective attention is just switching attention

SSVEP

steady state visual evoked potential

brain waves synchronise with flickering screen

• can study temporal attention

personality

stable behavioural traits

phineas gage

rod through head

• damaged frotnal lobas

• change in personality, not intelligence

• no impulse control, emotional cotnral, promiscuity

voles + vasopressin

administration

• male partner preference, selective aggression, paternal care

meadow vole: asocial + promiscuous

prairie vole: social monogamous

• praire vole had more oxytocin receptors and dense vasopressin strip

laws of gregor mendel

segregation: allele pairs segregate from each other during gamete formation

independent assortment: genes for different traits segregate independently

dominance: dominance decides expression of genotype

mice and burrow building

poliotonus: longer tunnels with escape routes (maniculatus)

• tunnel length is hereditary, monogenically (3 loci)

• escape tunnel is dominant trait (1 locus)

QTL

quantitative trait locus

• dna section that correlates with phenotype variation

foxes and tameness

heridty of tameness

• 103 loci were associated with tameness (qtl mapping

• SorCS1 gene: codes for synaptic plasticity and aids tameness

genetic archtiectures in humans

ACh system

inhibitory, fast, fast reuptake

norepinephrine system

fast acting and reuptake

dopamine system

hypothalamus and pituitary gland

serotonin system

5-HTTPLR

• variant associated with neuroticism

• account for 10% of phenotypic variance

• mutation: more amygdala activation

functions diffuse modulatory systems

regulate

• temperature (hypothalamus

• uterus contraction during labor and milk secretion (oxytocin

• blood pressure (vasopressin

• immune system (cortisol

• short-term feeding behaviour (dopamine, serotonin

• attention (norepinephrine

• sleep-wake cycles (serotonin

transgenerational epigenetic inheritance

new genetictheory

• unconventional

• there are heritable changes in gene activity without changes in DNA

• persistent over gneerations

  • depends on environment

histone marks

can modify histones at the tails

• chromatin state is dependent on the histone marks present

  • euchromatin (open) = transcription possibel

  • heterochromatin (closed) = no transcription

histone acetylation

acetylation —> dna around histone relaxes —> transcription

• inhibiting de-acetylation improves LTM

histone methylation

methylation marks affect chromatin state

• H3K9me3: open

• H3K9me2: closed

  • linked to contextual feal memory formation

CpG methylation

in CpG islands (areas with a lot of C ad G’s), a repressive mark can block transcription

• associated with contextual and auditory fear formation