Bio psych Flashcards

Question

What is the functional unit for an EEG?

Answer 1

• Functional unit is >10 000 simultaneously activated neurons ○ Meaning if you get more than 10 000 neurons in one place with the same orientation, then you can pick up signal with EEG

Answer 2

○ EEG is biased to signals generated in superficial layers of cerebral cortex on the gyri (ridges/peaks in brain formation) directly bordering skull ○ Signals from sulci (dips in brain formation) are harder to detect than from gyri and may additionally be masked by signals from the gyri ○ Meninges, cerebrospinal fluid (CSF) and skull smear EEG signal making it difficult to localise source - Known as the inverse problem □ If sources are known, resulting scalp reconfiguration of signals can be reconstructed, but reverse is not true - one scalp configuration of signals can have multiple dipole solutions

Answer 3

-From scalp in relation to reference electrode - To do this, can take average of all electrodes as reference □ However because brain has many dips and isn't perfectly round, so bit noisy to use average of everything ○ Reference should be a neutral point (eg tip of nose/behind ear) but some people reference to the average of all scalp electrodes

Answer 4

10-100 microvolts - Tiny signals so need to be amplified typically by a factor of 1 000 to 100 000 - Signal then digitalised (sample frequency is typically 256-1024 Hz but can be >4000Hz)

Answer 5

○ Signal is band-pass filtered to remove the low (<0.5-1Hz) and high (>35-70 Hz) because cannot reflect brain activity ○ Signal is notch-filtered (at 50-60Hz) to remove line noise which is also not brain activity - Attempting to remove those signals that are not from the brain

Answer 6

- Signals that are not brain signals ○ Eye blinks and movements have a strong impact on EEG signal because eye can be regarded as a dipole itself ○ Signals originating from the eye will contaminate the signal of interest - will be much larger ○ These signals can be recorded by placing electrodes next to and under the eye to capture vertical and horizontal eye movements ○ Eye-related signals can then be removed by excluding contaminated trials, or mathematical algorithms, such as independent component analysis (ICA)

Answer 7

-Not likely to be very good and are very noisy - not very useful when you need to find brain activity that is reliably related to cognitive processes of interest ○ Need to collect a large number of trials (eg 20) and average all of them to get a clearer pattern • There Is a lot of variance between sessions from same participants and between participants - even with averaging

Answer 8

• Average across all like events in the trials (eg in this example there were expected events and unexpected events - so need to average cognitive brain activity across all expected events and then separately average the activity in the unexpected events -- now you can compare the two) ○ Isolate where modulation of your brain activity occurs when comparing expected vs unexpected events

Answer 9

There are different aspects of the ERP component of interest that can be analysed - Peak amplitude (used in 70% of studies) - Area under the curve (because sometimes it is of interest that although a peak may be higher, it is also much narrower) (used in 20%) □ Narrow peak could represent that cognitive process finishes very fast, and wider represents a more ongoing process - Peak-to-peak (distance between negative and positive peaks) (used in 10%) □ The significance is in the rise of the peak, not the highest height ○ No clear rule - results may differ between measures ○ Another option is to determine the onset of a component - Looking at when a component starts to rise -Difficult to determine exactly when it is rising and when it is fluctuating

Answer 10

○ One reason is that many components are very well studied - Finding that a specific component is modulated by the experimental task might shed light on what cognitive process is involved

Answer 11

- Used N2pc component - known to index attention: strongest over the posterior cortex contralateral (opposite side) to where observer is attending (shifting attention without moving eyes) - Found that if you are attending to the left hemisphere/field, there will be a stronger (more negative) N2pc component in right hemisphere - Interested in difference between N2pc for right and left - Experiment: □ Asked participants to search for a target (coloured square open to the left) □ Need to ignore all distractors □ Can you do this by taking in an entire scene at once and finding it (parallel search - don't have to shift attention around) or do you need to shift attention around (serial search) □ Theory using N2pc - attention should only shift if need to serial search - If search is parallel nothing should change □ To get people to attend to one hemifield first - manipulated probability that a specific colour was the target - One had 75% one had 25% □ Prompted participants to quickly attend to the most likely colour first and researchers could monitor attention while participants were scanning field □ Tested what happened on trials where there was no target □ Found: - When no targets: found that when the two colours where in different hemifields of the screen, N2pc shifted - attention shifted to field with more likely colour then to less likely colour ◊ Serial search - Not much shift was shown when there were no targets and stimuli in same hemifield - When more likely stimulus was target and in different hemifield as other stimulus - no attention shift - When less likely stimulus was target and stimuli in different hemifields - attention shift □ Therefore attention only shifts when serial searching is used

Answer 12

□ Asked whether there is a cognitive mechanism for detection of and compensation for errors □ Asked participants to emphasise either accuracy or speed in a Flanker-task □ Incongruent displays should lead to more errors and error detection should only matter in accuracy condition □ Found: - ERN was strongest when emphasising accuracy, weakest for speed □ Is ERN indicative for compensating for errors? - It it did we would expect that ERN should also reflect attempt to break the error - Greater ERN lower response force (force at which they press button) - trying to correct error - Greater ERN, higher probability to get it right on next trial ◊ Successful learning from errors - Greater ERN, slower response on next trial

Answer 13

* Functional Magnetic Resonance Imaging * Creates an image - EEG and TMS don't * Good spatial resolution * Measure signal - BOLD signal * Use reverse inference to draw conclusions about cognitive processes from the presence of activation * We usually want to know something about cognitve processes * Know cognition happens in the brain * How much can we really learn about it? * Temporal resolution of fMRI is poor - takes a long time to record whole brain

Answer 14

• One method used to scan the brain was Positron Emission Tomography (PET) - involves administering a radioactive isotope to the patient ○ Exposes patient to significant amount of ionising radiation • fMRI - do not work with radioactive substances - super harmless

Answer 15

• Creates a magnetic field ○ 1.5-9 Tesla (usually 3T for most functional imaging) ○ Earth magnetic field is 65microT - fMRI is a very strong magnetic field ○ Cannot feel magnetic field - harmless • Patient placed on the bed and moved to centre of magnetic field • Head coil - like a helmet • Experiments can be controlled from outside scanner room - tests can be given to patients while in the fMRI machine • Can really investigate cognitive processes as you would in a lab • Cannot have any metal in the lab • Patient has a maximum of 1 mm movement - cannot move • Participants can see a projection (usually computer-controlled experiment) via mirrors mounted on the head coil • Responses can be given via scanner-compatible keys, joysticks, or a touchpad • Head position is fixed to avoid any movement

Answer 16

○ Human brain is 70% water ○ Hydrogen atoms can be thought of as small bar magnets "processing" (rotating) like a spinning top about an axis ○ Random spin directions of protons can be aligned parallel or anti-parallel to an externally applied very strong magnetic field in the MRI scanner - because they are a little bit like magnets ○ Align with the magnetic fields of the MRI but still processing about an axis - instead of doing it in random direction, now do it in systematic direction ○ Not perfectly aligned - also not static - keep processing in a random fashion ○ Some align with the field and some against, but most of them align with the field ○ Precession frequency of protons depends on strength of magnetic field ○ Axis along which the magnetisation is built up in the scanner = z-axis Magnetisation along z-axis cannot be measured A radiation frequency pulse (RF) is applied perpendicular to the magnetic field (delivered through head coil) Also harmless Frequency of the RF matches the precession frequency (frequency at which the protons 'process' about their axis) ○ Matching the frequency will cause the protons to absorb energy - has two additional effects - It tilts the magnetisation vector into the traversal plane (x-y plane) - Aligns precession of the spins - protons' rotations are in phase ○ The transversely rotating magnetisation vector can then be recorded as a signal - The head coil is used to send the RF pulses but it is also the receiver ○ Trick is to now switch off the RF pulse - After switching it off, transversal magnetisation decays - protons emit excess energy - Lose phase coherence - every proton does their own thing - still aligned with magnetic field by processing at different stages - Magnetisation along z-axis returns and transversal magnetisation disappears - processes are called relaxation - signal goes away - Independent ○ We are interested in how fast the signal goes away during relaxation - Summed effect of many protons undergoing relaxation is measured ○ Transversal magnetisation decays at different rates depending on the brain tissue (ie where in the brain) - One reason is because of proton density - lose coherence because they will be influenced by other protons in their environment - Different tissues have different number of protons ○ The signals from different protons will get out of phase with each other and begin cancelling each other out - Structural brain image depends on when signal is recorded during this process

Answer 17

• First step: divide brain into slices ○ Can now vary the gradient field along the z-axis and know that the different slices were exposed to different field strengths ○ Slice-selecting gradient ○ Thus if different protons are in different magnetic fields, precession frequencies will be different ○ Only one slice of the brain will be excited at a time using specific RF pulse because the precession frequency will not be matched for the others ○ By exciting one slice at a time we get the z- coordinate of all resulting signals • Now can use second gradient to change magnetic field within this slice - vary along the y-axis ○ Protons in each slice also have different precession frequencies ○ Gradient is called frequency encoding gradient ○ Gives us the x-coordinate of the measured signal • Finally, very briefly using a gradient along the y-axis causes protons to speed up their precession according to the strength of the magnetic field for a short time ○ When switching off this gradient, all protons are back to the same precessing frequency but are out of phase with each other ○ Phase encoding gradient • Allows you to specify the exact place within the brain after all three gradients because there is only one spatial position that could have a particular position/frequency • Now we know precisely what we have done to the protons at each location in space - can use technique called Fourier transformation to reconstruct entire space • Can measure slices in ascending, descending, or interleaved order to get 3D image of brain

Answer 18

- This whole process takes a lot of time to measure the brain just once • Usually measuring one full 3D image takes 1-3 seconds (1.5-2s is standard)

Answer 19

fMRI goes beyond MRI - measures brain activity | Images of the functioning brain

Answer 20

• Oxygenated blood, oxyhaemoglobin, is diamagnetic, enhancing the signal (signal gets better) • Deoxygenated blood, deoxyhaemoglobin, is paramagnetic - introduces field distortions (susceptibility artefacts) decreasing signal • Neural activity is accompanied by a local increase in blood oxygenation - brlood is pumped to that region ○ Oxygenated blood is needed for glucose metabolism • Neural activity is also accompanied by local oversupply in oxygenated blood and therefore gives a better Blood Oxygen-Level Dependent (BOLD) signal - large blood vessels cause 'brighter areas' (better signals) in the scans • This technique makes use of the fact that all neurons need oxygen supplied from the blood Means we can see local activity directly in the scans because the signal is slightly better • In a typical fMRI experiment, BOLD signal within a region is measured while participants engage in a cognitive task • Need to compare the activity against a control • Differences in BOLD signals tell us about whether a brain region is involved in a task

Answer 21

No: | measures BOLD signals - an indirect consequence of neural activity

Answer 22

The analysis of fMRI results: • Areas of enhanced activity can be mapped onto structural image of the brain ○ For the analysis, a General Linear Model is usually fitted to brain activity at each measurement point (voxel): significantly stronger activation in region X for task A compared to task B is interpreted as involvement of the region in task A

Answer 23

• Repeated measurement of brain activity is required for the whole brain while performing experimental tasks because signal is very noisy ○ Like EEG - need to average the activity after all the trials to get an accurate view of what brain regions are active

Answer 24

○ we have to be careful when interpreting differences in BOLD signal - If all these complex processes are driving the signal, it's not a one-to-one mapping onto neural activity ○ There is a substantial temporal lag between neural activity and the peak of the BOLD response - in the order of 8 seconds (signal reaches peak about 8 seconds after neural activity) ○ BOLD signal further needs up to 16 seconds before returning to baseline again • Not valid to compare signals between different regions of the brain because the signal change is different ○ Can only compare the BOLD signal in one region and then the BOLD signal in the same region for a different tasks

Answer 25

HRF is the measured response of different regions during fMRI (which look very similar in terms of shape)

Answer 26

• BOLD signal does not represent 'neurons firing' • Logothetis describes local cortical excitation-inhibition networks (EIN), small and highly interconnected functional microunits, which show massive recurrent feedback ○ Like when you and your group of friends are talking about going to the movie - lots of excitement with some very keen to, others not so keen to - doesn't matter if you reach consensus so long as there was excitement in your group ○ Not neurons firing or causing anything to happen, you can only see the interactions/excitement in the brain • Feedback processing within EINs (which determine what the output of the microunit will be) might account for most activity measured by the BOLD fMRI

Answer 27

• Problem 1: ○ Because we see blobs in the brain, the organisation of the brain's architecture must be 'modular' (brain has one functional unit in charge of each activity)? - This is not true - often we do not see the full networks involved - fMRI only shows 'tip of the iceberg' - Can never conclude that nothing else is going on than shown by BOLD signals - fMRI might not always map the functional units that matter - Just because it's what we see in our scans does not mean it is exclusively what is happening • Problem 2: ○ fMRI has poor temporal resolution (takes time) - Given that HRF is slow, very fast processes are very difficult to image - Because it takes about 2 seconds to measure the brain at once this does not allow exploring any processes that take place within these 2 seconds - We need to use some tricks in our experimental designs to separate events of interest if we don't wait for HRF to reach baseline every time • Problem 3: ○ Spatial resolution for fMRI is good but - It's also not great - smallest measurement unit is a voxel - a 3D pixel - Standard voxel size is 3x3x3 mm and we do not learn anything that happens within a voxel - But one voxel still contains >100 000 neurons • Problem 4: ○ Multiple comparisons problem - For such a complicated method only run a t- test for every voxel in the brain for comparison of condition A vs B □ Two values per voxel - However we have more than 50 000 voxels in the brain and we somehow need to correct for false positive findings (if it was caused by chance even if there is only 5% that it was) which are very likely to occur with so many tests □ 5% risk of making a false judgement with every voxel - this really sums up if we do it 50 000 times - Would expect 5000 false positives - Strictest correction of this is Bonferroni-correction - divide significance level by number of tests (eg voxels) and use this new significance level for each test - therefore overall risk of false positive will be 5 (or whatever the normal value is for p)

Answer 28

○ Presented participants with images of faces and contrasted BOLD signals to when participants saw objects (some faces some not faces) ○ Why is the brain so good at processing faces? ○ Found that a region located in the fusiform gyrus (in temporal lobe) responds more strongly to faces than to objects ○ They could show this result reliably in most of their participants, and could replicate it with different participants ○ Does that mean this area is specialised in the processing of faces? ○ To rule out this result being imply due to using objects as a control category, they replicated the study with a different control category: faces vs scrambled faces - Taking elements from the face and rearranging them so they no longer look like a face ○ The same brain area was strongly activated for faces but not for scrambled faces ○ Maybe it's the same for other body parts, not just faces - Contrasted faces with hands - Same brain region was activated with faces rather than hands ○ Led researchers to name the region 'fusiform face area (FFA)' - so sure this is the brain's module for face processing

Answer 29

○ Fusiform Face Area (FFA) ○ Parahippocampal Place Area (PPA) - houses and places ○ Extrastriate Body Part Area (EBPA)

Answer 30

○ 1: If our brain has one are specifically designated just to faces or places, what does that mean about other millions of objects we recognise? Not enough brain space - Could it be that it only looks like this region is specialised in faces - Gauthier et al. Greeble study: □ Asked participants to distinguish between different 'Greebles' - made up faceless figures which no participant had ever seen before □ During the experiment, participants learned the family structures and became experts for Greebles □ First, when they did not know much about Greebles, FFA responded strongly to faces, but not to Greebles as predicted □ However, after learning to distinguish really well between individual Greeble families, the FFA also responded for Greebles □ Therefore FFA is not a face area, it is an expertise area ○ 2: visual system might not be organised by specific object categories, but by where in our visual field objects are usually encountered - Organisation in ventral visual cortex might follow cortical topography (eccentricity mapping) - where do you usually encounter things - Coding is driven my resolution needs - FFA is good for everything that usually requires 'high' resolution, faces just happen to be centre of our vision - Face area corresponds to brain regions that would also activate when you focus on a very specific point - We encounter faces in the centre of our vision not the periphery - We usually need a high resolution to recognise faces, simply because we need to see the details - Might not be a matter of what it is but where it is - The module for places/houses is in reality better suited for processing the periphery - that's where house are usually encountered

Answer 31

• Researchers have found evidence for all three theories - suggested all might be true to some extent • The fMRI signal might therefore reflect a mixture of all three coding schemes ○ Can't tell from the BOLD signal that it's all true § Might be overlooking evidence that is equally likely to produce the results - 'tip of the iceberg' - does not represent the only thing that is going on

Answer 32

○ Argued that in order to represent all possible objects we know, objects must be represented in a distributed fashion - meaning all objects are represented in the entire 'object region' in the brain ○ In their study, they showed participants many exemplars for different objects - including objects - while fMRI was recorded - Ran correlations between distributed activation patterns for exemplars within object categories and between object categories - If the entire pattern codes for an object, then there should be high correlations for objects within categories as opposed with between categories - Found that correlations were higher within categories than between categories - This was still true when most responsive voxels for each category were excluded - eg FFA for faces (so basically when you don't consider the FFA, the correlations were still stronger when comparing face-face response as opposed to face-object response and the same for all of the objects) - Therefore throw away the brain area for faces and the brain still recognises faces - The distributed patterns of large and small responses, not just modules, were associated with the object categories

Answer 33

○ Usually apply following logic: - In this study, when task A is done, then region Z is active - In other studies, when cognitive process X happens, then brain region Z is active - Therefore, in this study, activity in Z --> engagement of cognitive process X ○ One problem is that the second point is not exclusive - brain region Z could be active for many tasks - Brain regions are very flexible ○ Problem is if we find activation in a region which is part of this multiple-demand network we still don't really know what the region is doing ○ If a brain region is activated by many cognitive functions, we learn very little from observing activation in those areas ○ How good is task A at manipulating the cognitive process X? - If the task measures more than one cognitive function, we also don't learn much ○ The probability of that we really learn from fMRI results that cognitive process X is involved depends on: - The quality of the task to measure the cognitive process - The specificity of region for this cognitive process

Answer 34

- Some researchers have concluded from looking at results from many studies that many anterior regions (towards front of brain) represent more abstract information, and more posterior regions represent more specific information - Others concluded that most regions in the frontal cortex can actually be found to be activated in many different tasks - Duncan argued that the frontal cortex shows relative, but not absolute specialisation □ Means prefrontal regions might just be recruited 'more strongly' if the task at hand becomes more difficult □ True for other regions too

Answer 35

○ What does it mean if you find that no region was significantly stronger activated for task A vs task B? - We don't really know ○ Our statistical tests are designed to make it difficult for the H1, not the H0, meaning we can't really interpret null results ○ Also don't know whether method might just not be sensitive enough to detect small differences (if just some neurons within each voxel might show differences, but not many, or there are neurons coding for both/many conditions within a voxel) - Should always avoid concluding that brain regions are not involved in a cognitive process

Answer 36

The building blocks of the genetic code

Answer 37

§ Adenine (A) § Cytosine ( c) § Guanine (G) § Thymine (T)

Answer 38

the building blocks of proteins - A specific sequence of three bases constitutes genetic code for a particular amino acid

Answer 39

○ 3 billion bases in the whole human genome | ○ 20-25 thousand genes that code for proteins

Answer 40

○ DNA helix is double stranded - Two strands carry redundant information - Each base pair has a partner on the other side □ C-G □ A-T - So if you know the base on one side you automatically know the base on the other ○ DNA bundled in chromosomes - Human karyotype comprises 46 chromosomes □ 22 pairs of autosomal chromosomes (1-22) □ Two sex chromosomes (XX/XY)

Answer 41

Sequence of 3 bases representing an amino acid

Answer 42

○ Function of a protein is determined by its structure ○ Structure of a protein is determined by its sequence of amino acids ○ A change to a single base can change the amino acid (not always) - Changing the amino acid can change the structure and function of the protein ○ A single-nucleotide polymorphism (SNP) is a position on the genome at which the base (nucleotide) differs between individuals - EG some may have a G where others have a T - The two alleles of a SNP are the alternative bases □ In this example, T is the major (most common) allele, and G is the minor - An individuals genotype at a SNP is determined by the two alleles on the copies of the chromosome - An individuals phenotype is the presence, absence or value of a trait of interest □ Psychological diagnosis (binary phenotype) □ Parenting style (categorical phenotype) □ IQ (quantitative phenotype)

Answer 43

○ Insertion-deletion variant - Bases added or missing (where one might have GCG, that is not in the other one) ○ Block-substitution variant - Multiple bases substituted ○ Inversion variant - Bases are replaced with reverse sequence of the other strand (so if the sequence on one is AATCG, the other one would have the backwards-version of the base pair: CGATT) ○ Copy-number variant - Sequence of bases repeated multiple times

Answer 44

§ Rare: <1% of alleles in population

Answer 45

Common: greater than or equal to 1% of alleles in population

Answer 46

one copy of the X chromosome in each cell is silenced or inactivated - This process is random in each cell ○ When there are two X chromosomes in one cell - XIST gene produces an RNA transcript (an intermediate step in the process of converting a gene encoded in DNA to a protein) that coats one chromosome, which is inactivated as a Barr body - TSIX gene on the other chromosome produces an RNA transcript that suppresses transcription of XIST - TSIX is antisense partner of XIST □ Both are encoded by the same stretch of DNA but are transcribed in opposite directions

Answer 47

○ Phenotypic variance (P) = variance from genes (G) + variance from environment (E) + variance from gene-environment interactions (GxE) + covariance between genes and environment (2covGE) ○ Heritability (h) is proportion of phenotypic variance due to genetic causes § H2=G/P § Local measurement: specific to a given population at a particular time § Varies with amount of variation there is in a population in genes and environment

Answer 48

§ Before advent of molecular genetics, used genetic epidemiology § Study designs in genetic epidemiology exploit the fact that related individuals share a predictable amount of genetic material § Eg twin studies: look at concordance in twins (if one twin has a trait or disorder does the other have it too?) □ Monozygotic (MZ) twins share 100% genetic material, dizygotic (DZ) twins share 50% genetic material □ Higher concordance in MZ pair than DZ pairs suggests genetic component ® Assumes they are equally similar environmentally

Answer 49

§ Dominant vs recessive: □ Dominant traits require mutation on one copy of the chromosome for expression of the phenotype □ Recessive traits require mutation on both copies (or only copy) of the chromosome § Autosomal vs x-linked □ Autosomal traits are carried on one of the first 22 chromosomes □ X-linked traits are carried on the x chromosome

Answer 50

- Dominant traits can't skip generations | - Two unaffected parents of a dominant trait cannot have affected offspring

Answer 51

Two affected parents cannot have unaffected offspring

Answer 52

Equally common in both sexes

Answer 53

- Cannot transfer father to son -If dominant: daughter of affected father must be affected - If recessive: Father of affected daughter must be affected ◊ More common in males

Answer 54

- Fragile X syndrome is monogenic disorder because we can tract its origins to a single gene -Can cause sever mental retardation - average IQ of 40 - Results from a copy-number variant of CGG sequence in the 5'-untranslated region (UTR - contains the promotor region where chemicals bind to start the process of transcribing a gene into a protein) of the gene FMR1 (fragile-X mental retardation protein) -FMR1 - critical to synaptic plasticity -Synapses to strengthen or weaken over time in response to increases/decreases in their activity - forms neural basis of learning - Expansion of the repeated CGG sequence of bases triggers methylation process (many repeated CGG sequences triggers methylation whereby chemical compound call methalyn binds to DNA) - Constricts the X chromosome and results in 'fragile' appearance ○ Methylated promotor region prevents transcription of the gene - promotor region also becomes bound by methalyn meaning it isn't there when it's required to allow synaptic plasticity

Answer 55

• Monogenic disorders ○ Can trace the origins to a single gene § Huntington's disease (HTT) § Fragile X syndrome (FMR1) • Polygenic disorder ○ Monogenic disorders are the exception to the rule in behavioural and psychiatric genetics § No single gene for schizophrenia, autism, bipolar disorder, depression or anxiety

Answer 56

• Examine the statistical association between a phenotype and many SNP markers throughout the genome ○ Typically 500 000 - 2 000 000 markers

Answer 57

• Can sample common variation sparsely (about 1 in every 1500-6000 bases is genotyped on average - median size of a human gene is 25000 bases) because linkage disequilibrium (LD) allows us to observe indirect observations ○ Chromosomes are mosaics and many variants are correlated • In a direct association the phenotype has a functional association association with a genotype (measured) SNP • In an indirect association, the phenotype has a functional association with a non-genotyped SNP that is in LD with a genotyped SNP Essentially: • We don't have to take huge samples, because even if the sample you take does not contain the SNP you are looking for, the linkage disequilibrium (LD) means the desired SNP can have indirect effects on the SNPs near it

Answer 58

-Used for quantitative traits ○ Categorise everyone according to whether they are a major homozygote, heterozygus, or minor homozygote - Plot phenotype score according to genotype - Is there a statistical association between the phenotypic measurement and the number of copies of the minor allele? - Could be used to determine frequency of alcohol use and IQ - (quantitative traits)

Answer 59

- used for categorical and binary (yes/no) traits -compare the case group with the control group ○ Is one of the two alternative alleles statistically overrepresented in a phenotypic group? ○ Could be used for diagnosing bipolar disorder (because it is a binary trait - you either have it or you don't)

Answer 60

- Graphically summarises reuslts of all individual tests of association - Each point represents outcome of a test for one SNP - Physical location of the genome and within a chromosome is on horizontal axis - Transformed p value is on vertical axis - Lower p values are higher on the axis - indicating strongest associations - Threshold for significance are stringent because multiple comparisons increase the likelihood of type 1 error - threshold is p=0.00000005 - Corresponds to Bonferroni correction for approx. 1 million independent uncorrelated tests

Answer 61

○ Predict genotypes at non-genotyped SNPs - Relies on data from a reference panel of individuals genotyped at high density § Applies patterns of LD discovered in the reference panel - use those to predict genotypes in non- genotyped SNPs independent of phenotype § Run those tests of statistical association as though though impudent SNPS were really genotyped

Answer 62

the frequency with which two markers are inherited together | ○ Helps define the region likely to contain the functional variant

Answer 63

the extent to which a sequence is maintained across species | High conservation suggests an important function preserved during evolution

Answer 64

○ Multiple SNP LD with a functional SNP | ○ Or multiple functional SNPs in the same gene

Answer 65

○ Meta-analysis of bipolar disorder GWAS found association with the ANK3 and CACNA1C genes § Proteins transcribed from both of these genes regulate the flow of ions in and out of neurons during an action potential § Both genes are down-regulated (much less of the protein is transcribed) by lithium § Lithium is an effective treatment for bipolar

Answer 66

○ Schizophrenia has previously been linked to abnormal dopamine signalling ○ Antipsychotic drugs block dopamine receptors - has been primary evidence in favour of the dopamine hypothesis ○ Find now from GWAS that DRD2 (a dopamine receptor gene) is associated with schizophrenia

Answer 67

○ In this case of schizophrenia, most significant association is the major histocompatibility complex (MHC) - MHC genes code for cell-surface proteins that allow the immune system to recognise foreign substances - Does acquired immunity play a role in the aetiology of schizophrenia?

Answer 68

○ Variants in the CHRNA5-A3-B4 gene cluster are known to be very strongly associated with heavy smoking § Encode subunits of nicotinic acetylcholine receptor, chlolinergic receptors that also respond to nicotine ○ Smoking has more than 80% prevalence in people with schizophrenia ○ Association of schizophrenia with CHRNA5-A3-B4 variants suggests heavy smoking may contribute to schizophrenia risk

Answer 69

○ Can result from complex interaction of genes and environment ○ Diagnostic categories § Individuals with similar symptomotologies may be given different diagnoses and individuals with the same diagnoses may share no symptoms ○ Interference of multiple deficits § Measuring any individual symptom is problematic when multiple deficits are present

Answer 70

- measure association between genotypes and quantitative endophenotypes (functional abnormalities associated with psychiatric disorder) ○ More immediate relationships with underlying genetic mechanism ○ Single quantitative traits § Relatively easy to measure reliably ○ Can use psychologically normal participants

Answer 71

○ Cognitive measures § Wisconsin card sorting test □ Given a set of cards with different coloured numbers of shapes on them, and need to sort the cards according to a number rule, a colour rule, a shape rule □ Then rule changes □ Interested to see how long it takes for participant to adapt to rule change ○ Neurophysiological measures § Pre-pulse inhibition of startle response ○ Psychomotor measures § Antisaccade oculomotor task □ Get participants to stare at a dot. The dot moves - but the task is to not follow the dot but move your eyes the same distance in the opposite direction □ Measurement of how well you can inhibit these very automatic movements ○ Anomalies of basic visual perception § Neural mechanisms particularly well characterised

Answer 72

○ Avoids difficulties assigning diagnostic categories ○ Allows testing of psychologically normal participants ○ Underlying biological mechanisms are likely to be simpler than for psychological disorders

Answer 73

• In a GWAS of visual sensitivity in a psychologically healthy population, the strongest association signal was at a marker on chromosome 1q21.1 ○ Known risk region for both schizophrenia and autism • The marker is situated in the 5'-untranslated region of the gene PDZK1 ○ If functional SNP is situation in the 5'-untranslated region, it likely effects protein trnascribtion rather than structure • PDZ proteins hold other proteins in appropriate configuration for localisation on the surface of cells ○ PDZK1 interacts with NMDA receptors § NMDA receptors play critical role in contrast gain control in the retina § Perceptual abnormalities in schizophrenia have been suggested to arise from NDMA receptor dysfunction ○ PDZK1 interacts with DLG4 § Disruption of DLG4 in mouse produces an ASD-related phenotype • Therefore, perceptual abnormalities observed in two different disorders may be linked by common genetic elements that affect synaptic function

Answer 74

○ Phenotype effect on genotype/mutation ○ Neural complexity and length of lifecycle are positively correlated ○ Techniques that rely on breeding multiple generations simply aren't feasible in more complex species

Answer 75

- Mutagenesis - introduces random mutations into genome of model organism - Mutagenised animal is then crosses (process of 'crossing') with a strand without mutations (wild-type strain) across several generations - Get offspring - look for the phenotype of interest - Take the offspring that exhibit the phenotype of interest and genotype them - So forward genetic is going from the phenotype and genotyping them to determine how they are genetically different from those not displaying the phenotype of interest ○ Advantages of using model organism: - Might have phenotypes available to use that aren't available in humans □ Eg anatomical phenotypes □ Learning phenotypes - Social behaviour

Answer 76

○ Targeted mutations are introduced and the effect of the phenotype is measured - Going from genotype to phenotype ○ CRISPR-Cas9 system is a natural part of a bacterium's defence against invading viruses - Can be used to create targeted genetic mutations in model organisms - Cas9 is a nuclease protein (a nuclease is an enzyme that can cut chains of nucleotides) - Guide RNA directs Cas9 protein to the desired DNA sequence, where the Cas9 cuts the DNA - The random repair process can disable the gene, or targeted sequences can be introduced to be inserted during repair

Answer 77

○ Not necessarily interested in determining the genetic causes of the behaviour, rather manipulating things at a genetic level so that we can better understand the links between brain and behaviour

Answer 78

○ Several types of microbial opsins that have been identified as suitable for optogenetic control - each type responds differently to light stimulation of particular wavelengths - ChR2 (channelrhodopsin-2 pump) □ After it's illuminated by blue light, lets positive ions (mostly sodium) into the cell □ Rapidly depolarises the cell and leads to excitation □ More likely to fire with blue light - NpHR (halorhodopsin) pump □ Activated by yellow light □ Lets negative chloride ions into the cell □ Leads to hyperpolarisation and neuronal inhibition □ Cell become less likely to fire with yellow light - They can be introduced into neural tissue by a viral vector □ Adeno-associated virus (AAV) is commonly used to introduce the required genetic material □ Using a virus to deliver material into cells to introduce new genetic material into cells by including the genetic code for the opsin genes with the virus □ By fusing these genes with the promotor sequences, get restricted opsin expression to particular cell types - Physically introduce the light into the brain to activate the rhodopsin pumps □ Delivered through implanted optic fibre □ When the pumps are activated, brings cells closer to action potentials - more likely to fire □ What behaviours are evoked or suppressed when particular cells are excited or inhibited?

Answer 79

• Combination of optogenetic system and CRISPR-Cas9 allows: ○ Light-controlled protein transcription - Can switch on or off activity of certain activities of certain cells using lights ○ Light-controlled genome editing - In animals DNA can be altered in cells using this combo

Answer 80

• Animal models ○ Genetic associations with ehaviour can only hint at the biological pathways involved ○ Using bioinformatics, can translate a human genetic mutation to target a homologous gene in a model organism ○ Model organisms allow more direct measurement at multiple levels - Structure - Function - Behaviour

Answer 81

○ Epileptic seizures arise from sudden excitation in groups of neurons with a loss of inhibitory potential - Reduction in amount of inhibition that is coming in to a particular neuron, which means that there is no limit to the excitatory input for the neuron, meaning the cell becomes overly excited - seizure ensues ○ Every neuron receives excitatory input and inhibitory input from other neurons - Information is added together and determines how excited a neuron is - In most normally functioning neurons there is a balance - With excitatory synapses, the most common excitatory neurotransmitter is glutamate - expelled from one neuron, crosses synaptic gap, and excites another neuron □ Role is to increase the spread of excitation with network of neurons - Most common inhibitory neuron = GABA □ Purpose is to increase nervous stability - reduces/impairs excitatory processes - With seizures - lack of normal balance between glutamate and GABA □ Insufficient GABA causes heightened excitability - seizures

Answer 82

○ Informed us more than any other condition about memory function ○ Definition - Recurrent, unprovoked seizures originating from medial or lateral temporal lobe ○ Simple partial seizures (without loss of awareness, originates in one part of brain) and complex partial seizures (with loss of awareness)

Answer 83

- Originate in one part of the brain, not the whole brain | - Not associated with loss of awareness

Answer 84

Associated with loss of awareness

Answer 85

○ Most common is hippocampal sclerosis (HS) - Neuronal loss and increase in gliosis (excess growth of glial cells (support cells that support surrounding neurons), after neuronal cell loss occurs in a region - take up space created by the death of neurons) - results in scar tissue (sclerosis) in hippocampus - Often occurs early in life - Other aetiologies include past infections, tumours, and vascular malformations (abnormally formed blood vessels in brain) - Form many people, medication is not enough for people to continue functioning in every day life - Surgical removal of the lesioned (damaged) hippocampus can cure or reduce the number of seizure

Answer 86

-HM was 27 and had severe temporal lobe epilepsy ○ Underwent bilateral resection (tissue was taken out of both sides of brain) of extensive amount of mesial temporal tissue - Included amygdala, most of hippocampi, part of parahippocampal gyrus ○ Memory post-op - Seizures were reduced - Tested before and after surgery - Normal attention span, preserved intelligence - Retrograde memory was largely recovered over time - only couldn't remember 6 months before operation - Severe anterograde amnesia □ Declarative memory impaired - Had to be moved to a highly supported residential house - Even after 10 months of moving in, couldn't find new home - got lost - Unable to recall names and faces of new people (even when he saw them every day) - Language largely frozen in 1955 - didn't pick up modern words or concepts (eg computers) ◊ Some exceptions (remembered rock and roll and Ayotollah - 20 years after surgery) - Remembered that his mother died (which happened after surgery) □ Procedural memory was normal - Could learn new skills even when he didn't remember learning them - Star-mirror task

Answer 87

Impairment of memories prior to injury

Answer 88

Impairment of memories after injury | Impairment in learning new information

Answer 89

Conscious access to previously-learned information

Answer 90

Remembering how to do something

Answer 91

``` ○ Mesial temporal lobe structures are essential for memory function - This surgery is no longer offered - only one side is removed now (and a smaller part) ○ Mesial temporal lobe structures more essential for anterograde memory ○ Distinction between Declarative and Procedural memory ```

Answer 92

○ Intact memory function does not solely rely on temporal lobes it relies on a neuroanatomical network involving many brain regions ○ Temporal Lobes are engine of memory - They are the primary key structures without which memory will not happen ○ Functional asymmetry - Left and right temporal lobes do somewhat different things

Answer 93

○ Patients have 'material-specific' memory deficits related to involved mesial temporal lobe (MTL) ○ Left MTL lesion results in verbal memory impairment ○ Right MTL results in non-verbal/visual memory impairment

Answer 94

* Located in mesial temporal lobe bilaterally | * Region of the brain first identified to support memory

Answer 95

○ Hippocampal formation and surrounding structures are essential for learning and consolidating novel information ○ Consolidation Theory: - After a period of consolidation, information can be retrieved independently of hippocampal formation involvement ○ Multiple Trace Theory (MTT): - Retrieval of autobiographical/episodic experiences always involves hippocampal formation ○ Particularly necessary for relational memory tasks ○ Paired associate Learning tasks - Required to remember an association between arbitrary (unrelated) pieces of information eg word and object

Answer 96

○ Information is integrated in sensory systems, sent to hippocampal formation for long-term storage ○ Memories can then be accessed by reciprocal connections between hippocampal formation and temporal neocortex

Answer 97

○ Papez's circuit ○ Frontal lobes (FL) Diencephalon

Answer 98

Papez circuit + Amygdala = Limbic system

Answer 99

Mammilliary bodies, fornix, anterior thalamic neuclei (ATN) (at the front end of thalamus), cingulate gyrus, and hippocampus

Answer 100

□ Lesions to components of the Papez circuit results in declarative memory impairment (poor relational memory/encoding) □ Declarative memory impairment more reliable when hippocampus or ATN are lesioned - it is fundamentally essential for memory function □ Difficult to be certain the extent to which reduced function to that particular area of the brain results in memory problems as opposed to the fact that making that area damaged also damages the connections that region has with other areas of the brain □ All parts of Papez's circuit are not equal - you are most reliably going to get damage to memory systems if one of two areas are damaged: hippocampus or ATN

Answer 101

- Motor programming □ Motor and premotor cortices (posterior FL) - Cognitive control processes eg problem solving, planning, reasoning, self-correction, and monitoring □ Prefrontal cortex (anterior FL)

Answer 102

□ Involved in developing and implementing strategies for appropriate memory encoding and retrieval □ In charge of the organisation of memory □ Impairment in remembering contextual details eg source of information, chronological order of memories (dosral lateral prefrontal cortex - DLPFC) □ Damage to orbito frontal prefrontal cortex (OFPFC), or ventromedial prefrontal cortex (VMPFC), results in confabulation - production of statements involving bizarre distortions of memory - May tell strangely bizarre stories that they tell as though it is a memory - they have no way of recognising what is a memory and what is not - the verification and filtering process is damaged

Answer 103

- 'interbrain' - At the back part of the forebrain - Made up of two structures - Thalamus - Hypothalamus

Answer 104

- Carefully structured so that different parts of thalamus connects with different parts of brain - Richly connected with all parts of the brain's cortex - Although thalamus is in the centre of the brain, it has strong connections with the outside cortical regions of the brain - Trying to understand its role in memory function is difficult - very few cases that have very discrete, specific, clean lesions to a very small focal area in 1 nucleus of the thalamus that does not affect surrounding nuclei - Anterior and medial lesions are likely to cause memory deficits than posterior or lateral lesions - Dense amnesic syndrome is associated with damage to the mammillo-thalamic tract (MMT connects anterior thalamus and hippocampus) - Cases with Dorsal Medial Nucleus, Midline and/or Internal Medullary Lamina damage but spared MMT show specific retrieval difficulties - similar to memory impairment after frontal damage - Damage to thalamic neuclei ◊ Dorsal medial nucleus: deficits in selecting the appropriate information to be retrieved ◊ Intralaminar/midline nuclei: deficits seen in memory retrieval and semantic memory

Answer 105

○ Plays key role in supporting memory for emotionally arousing/laden experiences - Classical fear conditioning - Facilitates rich representations of emotional experiences - Causes stress hormones (adrenaline and glucocorticoids) to be secreted from adrenal glands - cascading series of chemical changes occur - means that the amygdala uses these hormones to enhance the consolidation and storage of memory occurring in Mesial temporal lobes □ Increases ability to remember and learn in situations where there is a high degree of emotional richness in experience ○ Lesions result in - Loss of conditioned fear and impairment of new fear learning - Reduced memory for emotionally laden events

Answer 106

○ Electrical pulse sent down through a cell body's axon to the axon terminals ○ Allows communication with the cells it has synapses with ○ Action potential is generated in the Axon hillock (when the cursor is) - Propagates its way down the axon to the terminal projections by a series of jumps from node of Ranvier to Node of Ranvier - Each time it regenerates - it reaches the end of the axon with little loss of signal

Answer 107

- Nerve cells have resting electrical potential - they have the capacity to change their electrical voltage and at rest they have a particular potential - Resting membrane potential = -70mV - If the cell receieves excitatory input from other cells, then the electrical charge will go up (depolarising) - If it receives lots of inhibitory input it will hypopolarise - go down to less membrane potential than at rest - A cell always recieves both inputs □ It is added together and if excitatory input is greater than inhibitory input, and crosses over threshold of -55 mV, it sparks an action potential □ You don't need to have increasing excitatory input, you only need enough to push it over the threshol - The cell will fully depolarise - increase of voltage, it peaks and then drops away (and so too does the electrical potential - it will overshoot - be less than a rest, and then return to the resting potential) - The increase in excitation of the cell = excitatory post-synaptic potential (EPSP) - The result of the inhibitory input = inhibitory post-synaptic potential (IPSP)

Answer 108

- Inside each of the axon terminals are vesicles - When the electrical impulse arrives at axon terminals, it causes little gateways in the skin of the neuron to open □ Axon terminals are voltage gated - when they receive a certain amount of voltage, they will open and expel the vesicles into synaptic cleft (the gap between the axons and the dendrites □ The vesicles contain neurotransmitter, which crosses the synaptic cleft and bind with the receptors on the dendrites of the other cell □ The combining with the receptors results in EPSP or IPSP in the other cell

Answer 109

○ Learning involves synaptic plasticity (potential for synapse to change) - The biochemistry of synapses change to alter the effect on the post-synaptic neuron

Answer 110

- A long-term increase in the excitability of a neuron to a particular synaptic input caused by repeated high frequency activity of that input □ If cell A fires repeatedly and at very high frequency, the biochemistry of the connection with cell B will change - Seeing LTP: □ Measure baseline EPSP for a single electrical stimulus □ Then undertake process required for LTP - 100 electrical stimuli delivered rapidly □ The increased EPSP for subsequent single electrical stimulus - LTP

Answer 111

- LTP occurs when an axon of cell A excites cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells so that A's efficiency in firing cell B is increased

Answer 112

- Glutamate - excitatory neurotransmitter - Glutamate receptors are inserted in the post-synaptic membrane if LTP occurs - results in synaptic changes □ More glutamate receptors, so when glutamate is released across synaptic cleft, there are more receptors to receive it and add to EPSP - LTP causes a number of changes at the synapse that allows LTP to continue beyond a few hours, up to months □ Increased sensitivity of receptors to glutamate □ Increased amount of glutamate released by the pre-synaptic terminal button □ Protein synthesis in post-synaptic dendrites

Answer 113

- Occurs in hippocampus (particularly CA1 and dentate gyrus), also in entorhinal cortex □ Not just perforant pathway - Prefrontal cortex, thalamus, motor cortex, amygdala, visual cortex

Answer 114

- Long-term depression - opposite effect □ Low frequency stimulation at synapse can decrease synaptic strength - Habituation □ Repeated stimulation reduces the strength of synaptic response (reduced neurotransmitter released) - Sensitisation □ Single noxious stimulus causes a very exaggerated response in cell A in response to repeated presentation of noxious stimulus □ Results in exaggerated response to future presentations of noxious stimulus

Answer 115

○ Maintaining information over time ○ The mental processes of acquiring and retaining information for later retrieval ○ Timed component - can keep information and access it at a later time

Answer 116

○ Implicit/explicit memory - Nature of memory tasks define these terms □ Knowledge about the test which determines whether you are talking about someone's implicit or explicit memory - Do not measure cognitive theory or map onto neuroanatomy □ When you have damage on neuroanatomical structures, it doesn't discriminate clearly between implicit and explicit memory tasks ○ Procedural/declarative memory - Derived from dissociable cognitive theories □ We develop tests to test those theories - Measurement tools developed to test these theories - Map onto neuroanatomical systems ○ In studies of amnesia procedural/declarative distinction is more meaningful - because we are more interested in neuroanatomical structures and what damage to them means

Answer 117

○ Our ability to remember/store/learn skills and procedures ○ Important for motor performance ○ Supported by memory systems that are independent of hippocampal formation ○ Involves areas of brain like: - Cerebellum - Basal Ganglia -Does not involve medial temporal lobe, basal forebrain, or diencephalon

Answer 118

○ Accumulation of facts/data derived from learning experiences ○ Memory is outcome of processing by various higher-order systems, which feed into the hippocampal formation ○ Activation of declarative memory causes activation of related memories - Because of relational nature of hippocampal formation is so fundamental to declarative memory system, declarative memory is also in nature relational ○ Memory activation can be independent of environment - When you remember a particular experience, you have representational flexibility - can remember experience irrespective of whether you are in the same environment of when it happened the first time

Answer 119

○ Serial models - information is being process consecutively - Atkinson-Shiffrin model - Levels of Processing model - Tulving's model ○ Parallel model - memory processing is all happening at the same time in parallel with one another - Parallel Distributed Processing Model

Answer 120

○ Information fades very quickly ○ If it isn't tended to it is lost, if it is attended to it will move into working memory ○ Sensory memory: Iconic (visual) and Echoic (auditory) ○ Working memory is a capacity-limited system - Miller's notion that we have 7+/2 items of information that can be processed at any given moment ○ Sensory memory and working memory represent short- term memory ○ Long-term memory is much more stable - Where information from WM is encoded into long- term memory store - Doesn't create absolute truths of an event - Memories are based on your own personal perceptions and interpretations of what’s happening - not objective replay of what happened - Tend to encode this info based on schemata - notions of what you expect to be happening and why things are happening - When info is rehearsed, information will be added and that will affect memories being stored in long- term memory - Info is stored in long-term memory in a semantically meaningful way (in a way that makes sense to you)

Answer 121

○ Craik and Lockhart, 1972 - More interested in long-term memory - How likely was it that someone will remember something ○ Information retained according to level of processing it has undergone - Shallow-deep continuum □ Shallow memories are more fragile, can be more conceptualised like short-term memory (though not entirely) □ Deep memories are more durable memory traces □ Depends on how much processing that has occurred to that memory as to how durable/fragile it is - Maintenance vs elaborative rehearsal □ Maintenance rehearsal: - Repeating information to yourself in the same way it was presented - Results in shallower memory - less durable, more easily forgotten □ Elaborative rehearsal - Process information and try to integrate it with prior images and experiences, to understand the meaning/interpretation and incorporate it into existing semantic network - Deeper levels of processing - Analysing info based on meaning - will end up with more durable memory traces

Answer 122

``` ○ Came out of lesion studies - not based on normally functioning people as the previous studies were ○ STM - LTM (like Atkinson-Shifrin model) ○ LTM - Procedural □ Remember how to do something - Episodic □ Remember events - Semantic □ Knowledge of facts ```

Answer 123

○ Information is not sequentially processed ○ There is a distributed network of connections and activations happening simultaneously in parallel ○ A given memory is just the activation of the connection in different areas ○ A different pattern of activation with different strengths of some connections and less in others is what distinguishes one memory from another ○ Come out of computer modelling literature - Places emphasis on linkages and connections rather than the elements/nodes themselves ○ The pattern of activation that you see at a given time that results in that experience of memory or knowledge ○ Learning occurs by changing that pattern of activation - Strength of connections is changed between relevant sites

Answer 124

○ None of the models fully account for all the research data in isolation ○ All the models are true in different ways ○ Serial models are most useful for studying amnesia - Tulving's model is most useful because it has been most useful in understanding what is going on for individuals who have damage to memory systems

Answer 125

○ The knowledge of an event or fact, of which meantime we have not been thinking, with additional consciousness that we have thought of or experienced it before - Describes episodic memory - refers to ability to remember events as opposed to facts

Answer 126

○ A memory system that makes possible 'mental time travel' through subjective time, from the present to the past and the future, a feat that other memory systems cannot do ○ According to Tulving it works by - Allowing individuals to re-experience, through autonoetic awareness, previous experiences and to project similar experiences into the future □ Autonoetic awareness - highly personalised feeling of reexperiencing oneself in the autobiographical past or present □ Sense that this is your personal experience/memory that you are retrieving from memory banks - Allows people to have a conscious recollection of their own personal past ○ Episodic has developed more recently in terms of evolution ○ Develops late in childhood ○ Dependent on semantic and other forms of memory ○ Shares neural mechanisms and cognitive processes with other systems ○ Is additionally subserved by specific mechanisms and process that are not components of any other systems

Answer 127

○ Knowledge memory ○ Memory system that allows us to acquire and retain factual information ○ Not purely concerned with language or verbal information ○ No autonoetic awareness of personal past

Answer 128

- Declarative memory is reliant on the hippocampal network - Damage results in equal impairment to the episodic and semantic memory systems - They operate in parallel - neither is reliant on the other system, but they both depend on the hippocampal system - Amnesic patients have equal difficulties with event and fact memory

Answer 129

- Serial Parallel Independent hypothesis (SPI) □ Encoding is serial, retrieval is parallel □ Encoding into semantic memory depends on semantic system □ Encoding into episodic memory depends on semantic system □ Episodic memory is a unique extension of semantic memory □ Retrieval is independent, and can be supported by either system independently of the other □ PRS = perceptual Representation System - perceptual memory system □ Allows for some predictions for how some people will behave with different types of measures depending on what is damaged in the brain - allows us to predict and test whether model is accurate or not - By determining whether there are dissociations between different aspects of this model - You can have no dissociation, single dissociation or double dissociation - Can use this to determine what role a part of the brain is having in different processes/cognitive functions □ Encoding has a single dissociation, retireval has double dissociation

Answer 130

• You have system with X and Y parts - do they work in parallel to produce A and B outcomes, or can they dissociate (is there some degree of independence? ○ No dissociation: damage to X results in damage to A and B equally, and the same for damage to Y ○ Single dissociation: You damage X and it only affects A and not B, but damage to Y damages A and B equally ○ Double dissociation: You damage X and it only affects A, you damage Y and it only affects B

Answer 131

○ Television with X and Y components - Are both colour (A) and picture (B) equally dependent on X and Y components? □ If you lose X you can lose colour (A), but still have picture (B) □ If you lose Y you can lose colour (A) and picture (B) - Single dissociation - both A and B rely on Y, but A also relies on X

Answer 132

○ Television with transmission Y and Z componenets: are picture (B) and sound ( C) equally dependent on Y and Z? ○ You damage Y and lose picture (B), and still have sound (C ) ○ You can damage Z and losesound (C ), but keep picture (B) ○ Double dissociation - B independently relies on Y and C independently relies on Z

Answer 133

• Investigated 3 patients who suffered very early bilateral medial temporal lobe injury ○ Beth - 14 y.o. at assessment - Had heart attack at birth (heart stopped 7-8 minutes) - 2 hours after resuscitation had generalised seizures - Good recovery after 2 weeks - Memory difficulties noted when she was 5 and started school ○ Jon - 19 at assessment - Premature baby (26 weeks) - On incubator for 2 motnhs (tube fed and ventilated) - Afterwards developed normally - Age 4 - had 2 protracted, afebrile convulsions (2 long seizures without fever - 1.5-2 hours each) - About 1.5 years after that, parents noticed severe memory impairments (entering schooling) ○ Kate - 22 at assessment - Up until 9 she was an avergare student - At 9, she took a toxic dose of asthma medication - Number of seizures, was unconscious, and had respiratory arrest (stopped breathing) - Left her profoundly amnesic - Age 17 developed temporal lobe epilepsy, well controlled with medication • Neuropathology ○ They were assessed with MRI and spectroscopy ○ All have abnormally small bilateral hippocampi ○ All have intact extra-hippocampal temporal lobes • All 3 cases had very significant impaired memory capacity relative to intellectual capacity ○ Memory capacity is proportional to intellectual capacity • Memory assessed with standard clinical measures of memory (tests of episodic memory) • Memory was so impaired they could not function independently ○ Every day memory deficits include - Spatial memory □ Couldn't find their way around - Temporal memory □ Couldn't remember day/time - didn't know what class to go to - Episodic memory □ Didn't remember what they'd done during the day • Educational achievement ○ All faired relatively well in mainstream education ○ Educational achievement is consistent with IQ - Important because educational achievement essentially relies on factual knowledge - semantic memory system ○ All had factualy knowledge within the normal range • Conclusions ○ Intact semantic memory, impaired episodic memory - These systems must be functionally dissociable (single dissociation) ○ Episodic memory relies on hippocampal memory circuit

Answer 134

• V-K study findings fit with Tulving's SPI model ○ Episodic memory function relies on semantic memory ○ Semantic function does not rely on intact episodic memory • However, people with semantic dementia have impaired semantic memory but intact episodic memory ○ Means double dissociation is possible • It is meaningful to consider episodic and semantic functions as separate from each other, but need to use this as a heuristic guide rather than an absolute truth to understand patient populations who differ in semantic and episodic memory ability ○ Interaction between systems occurs, but it is not yet fully understood

Answer 135

○ Commonest primary dementing illness (where disease process itself operates directly on neuronal tissues) - Autopsy studies report approx 50% of all dimensias are AD ○ Very affected by age - Prevalence: approx 2% in age bracket of 65-70 □ 20% of people over the age of 80 have AD - Problem of ageing population □ Largest group of people is baby boomers □ Eventually become dependent and enter supported accomodation □ Will be very costly to look after them all

Answer 136

Diagnosing - Diagnosis can only be made through pathology □ Definitive diagnosis: if we have a bit of brain under microscope and find very specific features in brain tissue □ That happens through two mechanisms: - Biopsy living person's brain - Look at brain in autopsy after death □ What actually happens is we can only diagnose dimentia of the Alzheimer's type (DAT) - Syndrome that occurs in those people who are shown to have AD at death - Compilation of symptoms that people who are later found to have AD demonstrated

Answer 137

- Majority do not have family history - occurs sporadically: especially with late onset (AD after 60-65) □ Only genetic relationship that has been found is on the ApoE gene (epsilon 4 allele of apoliprotein E gene) - Shown to elevate risk of developing AD - Only gene that has been shown to have any relationship with late onset AD

Answer 138

- Rare, early onset AD (before 60-65) - autosomal dominant cases □ Where lots of people in the family across generations have early onset AD □ Mutations in 3 genes: - Amyloid precursor protein (APP) ◊ Important in development in amyloid ß peptide - Presenilin 1 (PSEN1) - Presenilin 2 (PRSEN2) ◊ Both PRSEN proteins are involved in converting APP into Aß peptide □ All alter production of amyloid ß (Aß) peptide - principle component of senile plaques

Answer 139

- Individuals with Down Syndrome □ Unusually prone to developing AD □ Develops very early - approx 40

Answer 140

□ No one particular thing that trigger onset of AD □ Some suggestion that head injury results in increased risk, but issue is that the science isn't great quality - Only for moderate to severe head injury in males

Answer 141

□ Many people who have a stroke, or brain infection, radio therapy in cancer treatment who seem to develop AD shortly after □ However, we know that with these people they already have subclinical disease going on - Not severe enough to bring it to medical attention - Have this experience of stroke (for eg), results in decompensation (brain doesn't recover as well as expected), and reveals subclinical AD that is going on in the background - Doesn't mean the stroke caused it, it just revealed the symptoms that have slowly been developing

Answer 142

○ Onset: insidious - Do not wake up suddenly with symptoms, they develop slowly in an increasing way over a number of years - Usually 1-2 years prior to diagnosis ○ Course: slow deterioration in function - Over a number of years - Occasionally see plateaus in deterioration □ Doesn't tend to lengthen period of disease process, just slows it down for a period of time before it speeds up again - Death: mean is 8.5 years after onset (range is 2-20)

Answer 143

- Phase 1:lasts 2-3 years □ Failing memory (amnestic presentation) □ Muddled inefficiency in Activities of Daily Living (ADL) □ Spatial disorientation - Particularly at night □ Mood disturbance can occur (agitated or apathetic)

Answer 144

- Phase 2: more rapid progress of deterioration □ Intellect and personality deterioration □ Focal symptoms appear - Dysphasia ◊ Anomia: word-finding difficulties - Dyspraxia ◊ Can do motor movements required for an activity, but have trouble sequencing their motor movements - Visual Agnosia ◊ Despite eyes functioning normally, unable to recognise what visual objects are - Acalculia ◊ Complete loss of function ◊ Cannot calculate because no longer understand arithmentic function in the same way - understand that 10 apples is more than 3 oranges, but do not know how to multiply, divide and then add and subtract - loss of arithmetic function) □ Disturbance of posture and gait - increased muscle tone - Look stiff when they move □ Delusions/hallucinations can occur

Answer 145

- Phase 3: terminal stage □ Profound apathy - become bed ridden □ Eventually lose neurological function □ Bodily wasting occurs - Because not eating □ Usually people will die from pneumonia because they're no doing anything or eating much

Answer 146

- Probable AD □ Deficits in 2 or more areas of cognition - Amnestic presentation: most common - Nonamnestic presentations: language, visuospatial, executive dysfunction □ Progressive worsening of memory and/or other cognitive functions - deteriorating process □ No disturbance of consciousness □ Onset between 40 and 90 □ No other reasons for deterioration □ Biomarkers are not required - Biological markers that are typically seen in blood, and it says in probably AD - if you have presence of certain biomarkers, it increases likelihood that you have probable AD, but not having them doesn't mean you don't have probable AD - Possible AD □ Made on the basis of dimentia syndrome if there are variations in the onset, presentation, or course - Like Probable AD but less certain - slight variations □ Can be made in presence of other disorder, which is not considered to be the cause of dimentia - Definite AD □ Need histopathological evidence of AD obtained from biopsy or autopsy - Need evidence of specific abnormality at level of the cell

Answer 147

○ Grossly atrophied brain (shrunken look because of death of neurons) - Affects frontal and temporal lobes, and less obvious is parieto-occipital regions ○ Extensive degeneration of neurons - Loss of cholinergic neurons, which introduce acetylcholine (neurotransmitter) into synapse) ○ Accompanying glial proliferation ○ Extensive amounts of senile plaques (contain Aß peptide) - Senile plaques - histological structure that contains Aß peptide, particularly present in hippocampi and amygdaloid nuclei ○ Extensive amounts of neurofibrillary tangles (NFT) - abnormal form of tau protein - NFT occur diffusely through grey matter particulalry in hippocampi - As a major component they have tau protein ○ Intensity of neuropathological features (esp tau protein) correlates closely with severity of dimentia

Answer 148

- Presence of senile plaques and NFTs commence in hippocampal formation and mesial temporal lobes - Particularly NFT - have predominance in this region Pathology spreads posteriorly towards parietal cortex Then spreads ultimately forwards to involve frontal cortex Spread of disease is different to the atrophy Also spreads to lateral and posterior temporal lobes Eventually the whole neocortex is affected Onset of neuropathological changes commence many years before symptoms are experienced (Preclinical stage) Tau pathology is most related to symptom expression of cognitive difficulties and dementia stage

Answer 149

○ Initially see MTL (mesial temporal lobe) memory impairment due to early predominance of hippocampal/MTL involvement (Tau pathology) - episodic memory impairment - Anterograde memory: □ Impaired new learning □ Impaired delayed recall □ Poor recognition memory (prompts do not assist recall) - Retrograde memory □ Intact for remote memories □ Reduced for recent retrograde memories - As memories get closer to where they currently are, they have more difficulty - temporal gradient - Develops as disease develops ○ Wernicke-type aphasia - Word-finding difficulties - Fluent (grammatically correct speech) ○ Visuospatial deficits and topographical disorientation due to spread into parietal lobes - Dyspraxia - Visual agnosia - Acalculia ○ See behaviour change due to spread of disease into frontal lobes - Apathy - Agitation ○ Eventually disease affects all of neocortex, see generalised impairments in all domains ○ Must see functional impacts for a diagnosis of dementia

Answer 150

○ Some pharmacological treatment has been developed - Work by trying to rebalance the action of acetylcholine - Prevent the reuptake of acetylcholine from the synapse through deactivating the molecules that encourage the reuptake of it back into the cell ○ They are not particularly effective - work for a couple of years, and maintain the current quality of life for longer so they don't get worse, but they ultimately stop working and then the person's disease process speed up to where it otherwise would have been - life expectancy doesn't change ○ Considerable research is being done in this area ○ No clear evidence that anything we have or can do prevents AD - Diet and physical, social, and cognitive activity can help in reducing the risk of cognitive decline in AD

Answer 151

○ Changes that occur in AD also occur in normally ageing individuals - Pathological changes are much more severe in AD ○ Cognitive deterioration evident in normal ageing, but in DAT cognitive function is significantly impaired relative to same aged peers

Answer 152

0.15 quadrillion

Answer 153

○ Located on the outside of the cell membrane allow the released neurotransmitters to influence post-synaptic neurons ○ Each receptor can only be activated by one neurotransmitter (or a drug that is designed to mimic that neurotransmitter) ○ Have very specific function/action - When neurotransmitter binds to the receptor it will trigger the same event every time (either opening a channel or triggering a second messenger event) - Not simple 'open/shut' gates - have complex structures and it is often a small change in their shape that will 'open' their channel

Answer 154

- Ion channels | - G-protein coupled

Answer 155

□ Act like gates for ions □ When a neurotransmitter binds onto the ion channel, it will cause a change in receptor shape and will allow ions to flow through □ Normally selective and only allow one of a few types of ions to pass through when they are open (eg calcium channel)

Answer 156

□ Work through second messengers □ When neurotransmitter binds to receptor, it activates a second messenger system that can either open a channel or cause other things to change within the cell (eg DNA being transcribed and new proteins being made) □ Effectively gives energy to a second messenger system - allows attached enzyme to do its thing

Answer 157

○ Chemical substance released from neuron at an anatomically specialised junction (synapse), which diffuses across a narrow cleft to affect one or sometimes two postsynaptic neurons, a muscle cell, or another effector cell - Very direct communication between one neuron to the next - Directly impacts activity or subsequent cell ○ Either excitatory or inhibitory ○ Serves rapid (millisecond), precise, point to point communication

Answer 158

○ A chemical substance is released from the neuron in the central nervous system, or in the periphery, that affects groups of neurons, or effector cells with appropriate receptors - Doesn't have to be released at synaptic sites - Often acts through second messengers - Can produce long lasting effects - Doesn't have single impact on subsequent neurons - it's about modulation of neural activity ○ Slow (milliseconds to seconds) processes that alter the subsequent responsiveness of neurons • Presynaptic ○ Alters neurotransmitter release • Post synaptic ○ Alters neurotransmitter action (eg alters excitability/firing pattern) • Neuromodulation may cause changes in neural function or structure (ie sustained neuromodulator activity can drive changes in the brain related to synaptic plasticity

Answer 159

* Synthesis and transport to the synapse is relatively slow | * But the neurotransmitter action is extremely fast because it sits ready for release

Answer 160

○ Act by mimicking neurotransmitter/modulator ○ Can act as agonists - Activating the receptor like the natural compound ○ Or an antagonist - Blocks receptor and prevents natural compound from activating it

Answer 161

``` ○ 1: Synthesis ○ 2: Relase from synaptic vesicles ○ 3: Bind to receptors ○ 4: +/- influence on post synaptic neuron ○ 5: broken down by enzymes ○ 6: Re-uptake of transmitter ○ 7: Formation and storage in synaptic vesicles ○ *Drugs can affect all stages* ```

Answer 162

○ Neurotransmitter can be altered by increasing or decreasing synthesis of the neurotransmitter

Answer 163

* Signalling molecules produced by glands and transported through bloodto regulate physiology and behaviour * While they are chemical messengers, they are produced in glands rather than neurons, and circulated by the blood

Answer 164

• Do not satisfy all criteria for a neurotransmitter, which are: ○ Present in synaptic terminals ○ Released from presynaptic terminals after neuron fired ○ Existence of receptors on postsynaptic neurons

Answer 165

Peptides Nucleosides Lipids Gases

Answer 166

- Compounds that consist of 2 or more amino acids - Not synthesised from smaller compounds, but are a product of larger protein molecules (poly-peptides) being broken down into peptides within the neuron before release at the terminal button - Most peptides serve as modulators, however many peptides known to be hormones also act as neurotransmitters and are often co-released with other neurotransmitters - Same compound having different roles and functions in different contexts in brain regions - Best known family of peptides are endogenous opiods □ Highest density of opiate receptors are in areas involved in pain - Examples □ Heroin □ Morphine □ Opium

Answer 167

- Not neurotoxic - doesn't damage brain cells - Can cause death by respiratory failure - Destroys person's life, not brain - so addictive - Full agonist at opioid receptors - Pleasant effect - causes people to want it again - Types of treatment to heroin dependence or overdose ◊ Buprenorphine - Partial agonist - Treats dependency - Activates receptor to smaller degree - don't get same high - Still addicted but to buprenorphine not heroin ◊ Naloxone - Full antagonist - Works quickly - Can block effects of heroine - Used for overdose - Stops effects like a plug - Rapid withdrawal ◊ Methadone - Agonist - Used in treatment of dependency - Much slower time course than heroin - If someone had both heroin and methadone, it blocks heroin's ability to activate the receptors - Need to take it for years - allows them to live their lives

Answer 168

- Subunit of necleic acids □ Hereditary-controlling components of all living cells such as DNA and RNA - Usually obtained by chemical/enzymatic breakdown of nucleic acids - Often co-transmitters hat serve to modulate the release of other transmitters - modulating the modulators - Adenosine □ Forms from breakdown of adenosine triphosphate (ATP) - Primary energy source in cells for transport systems and many enzymes □ When you are awake levels gradually rise - part of energy biproduct - Body uses that biproduct of energy consumption to trigger sleep and suppress arousal - The more excersise and energy you burn triggers a sleep-promoting response □ At synapses where adenosine is the primary neurotransmitter, a high post-synaptic firing rate leads to sleepiness - Increased firing = reduction in arousal - Caffeine □ For plants, it acts as a pesticide that paralyses and kills insects that attempt to feed the plants □ Acts as adenosine receptor antagonist - Blocks natural action of adenosine □ Because adonsine increasing firing rate increases sleepiness, caffeine increases alertness by reducing the firing/activation of these neurons □ Different to other stimulant drugs - doesn't act as a stimulant, but blocks sedation effects

Answer 169

- Naturally occurring molecules that include fats, waxes and many others - Hydrophobic - repel water - Main biological function is energy storage, signalling, and provide the structural components of the cell membrane - Synthesis pathways remain unclear for many lipids that serve as neurotransmitters/modulators - Endocannabinoids □ Internal cannabis-like substances □ 2 known cannabinoid receptors: □ CB1 - Found in the brain - Responsible for the main psychological effects - Receptor activation: shortens the duration of action potentials in presynaptic neuron - decreases amount of neurotransmitter released □ CB2 - Found in peripheral tissue □ By regulating the activity of those neurons and release of neuromodulators, these receptors act to modulate the modulators - Cannabis □ Active component is tetrahydrocannabinol □ Dried and consumed by inhalation □ Effects range from change in appetite, time perception, arousal (relaxation/anxiety), and have been linked to states of apathy and underachievement □ Used to reduce nausea, relieves asthma attacks, decreases pressure within the eyes in glaucoma □ Multiple epilepsy trials are underway

Answer 170

- Air-like fluid substance which expands freely to fill any space available - Soluble gasses - dissolve in fluid (dependent on pressure and temperature) - Neurons use two gasses as neurotransmitters □ Nitric oxide - Produced from amino acid Arginine in subpopulation of 1-2% of neurons in cortex - Exact function and role in the brain is unclear ◊ Involved in learning and memory through effects on synaptic plasticity ◊ Dilates blood vessels in regions of the brain that become metabolically active - Very different to traditional neurotransmitters ◊ Not synthesised or stored in vesicles ◊ Produced throughout the cell including dendrites and defuses out of cell as soon as it is produced ◊ Does not activate receptors, simply enters neighbouring cell ◊ Very short lived and is degraded or reacted within a few seconds of being produced ◊ Can act on several nearby neurons ◊ Short half-life - doesn't flow around brain with huge effects □ Carbon monoxide

Answer 171

○ Main excitatory neurotransmitter in brain - When glutamate is released - increases chance of post-synaptic neuron firing ○ Released by all excitatory neurons ○ Estimated that over half of brain synapses release glutamate ○ Glutamic acid (one of the amino acids) ○ Synthesis: - Amino acid that acts as a neurotransmitter in its original form, but this amino acid does not pass through blood-brain barrier, so it still needs to be synthesised in the brain - Is synthesised from glutamine which is released by cells neighbouring the neurons

Answer 172

``` - 4 major types □ 3 of which are ion channels - NMDA receptor (only need to worry about this one) - AMPA receptor - Kainate receptor □ 1 is G-protein-coupled (metabotropic) - The metabotropic glutamate receptor ◊ Allows changes using secondary messengers ```

Answer 173

* Found in most long projection neurons throughout the cortex * Excitatory connections are 'point-to-point' * Many region-specific functions * Information flows through visual hierarchy

Answer 174

○ There is also a glycine molecule (another type of amino acid) ○ If magnesium ion is not bound to the inside

Answer 175

-NMDA is particularly complex -6 different binding sites so has lots of complex functions • Other binding sites modulate receptor function • NMDA receptor is critical for learning, memory, perception, and synaptic plasticity in general • Large genetic studies identify NMDA receptor as relevant for schizophrenia, but also to general function and IQ ○ Hard to tease things apart - can't block all NMDA receptor to see - end up comatosed

Answer 176

○ NMDA antagonist - Blocks NMDA receptor ○ Reduction in glutamate is believed to contribute both to the general sedative and memory effects of alcohol - Information is not coded as well as it could be ○ Also GABA agonist which further leads to brain inhibition - GABA is an inhibitory neurotransmitter ○ Drug is both blocking 'activation' neurons, and activating inhibition neurons

Answer 177

○ PCP - Phencyclidine 'angel dust' ○ Ketamine - 'special K', horse tranquilizer ○ Both are NMDA antagonist ○ Both cause dissociative hallucinations (people feel disconnected rather than perceiving visions) ○ Risk of suicidal behaviour ○ ketamine itself is remarkably safe on body - Often give ketamine to different sized animals, kids, or in war time (so can't always measure appropriate dosages according to body types) because it is very unlikely to experience overdose in terms of heart or breathing failure - can use it on different body sizes - Also anaesthetizes person/animal with eyes open - good for animal studies because you can check pupils etc - Not used heavily in usually hospital environments because causes unpleasant experiences - dissociations and risk of suicidal behaviour

Answer 178

* Psychosis - symptom cluster, not a diagnosis * Schizophrenia - ~1% population * Psychotic symptoms may effect 3% of population at some time in their life * Prominent feature of schizophrenia, but exists in other conditions * Can have drug-induced psychosis

Answer 179

``` ○ Delusions ○ Hallucinations ○ Depression ○ Anxiety ○ Suicidal thoughts or actions ○ Difficulty functioning ○ Disorganised speech - switching topics erratically ```

Answer 180

* Suggested link between Glutamate and psychosis, but it is contraversial and is likely to involve other neurotransmitters such as dopamine * Regardless of exact neurotransmitter involvement, the symptoms suggest widespread disruption and lack of coherent integration of sensory information * Genetic studies point to a large number of genes rhat all may contribute to a small amount of risk for psychosis * Very unclear, and may just reflect altered synaptic activity (communication between neurons) in psychosis

Answer 181

• No major structural differences in psychosis | ○ Illustrates the importance of chemical balance in healthy perception and cognition

Answer 182

○ Previously healthy female was hospitalised with acute psychosis ○ Treated her wth medication but found her state deteriorated ○ Scan of brain and spine showed no problems ○ Did have an autoimmune response to NMDA receptor - Body was fight NMDA receptors - Caused complete dysfunction of NMDA receptors - Ended up comatosed ○ About 75% of people in these cases (NMDA receptor encephalitis) recover completely - Rceovery occurs in step-like manner in reverse order □ In some cases experience intermediate bouts of psychosis as they improve until final recovery

Answer 183

• Gamma-amino butyric-acid • Primary inhibitory neurotransmitter ○ Decreases likelihood of post-synaptic neuron firing • Without inhibitory synapses, brain would cascade into endless firing ○ Uncontrollable state ○ This is what happens in seizures • Most short local neurons are inhibitory, so they form a dense web around and between excitatory neurons • In healthy brain, GABA helps delicate coordination of neurons to signal very specific information • Neurons are selective but not perfect ○ Inhibitory networks reduce likelihood that neurons will fire for their non-preferred stimulus • Doesn't determine what information is being passed on, but increases selectivity of glutamate signal being passed around brain • Produced from glutamic acid ○ Same amino acid as Glutamate • Glutamate is converted into GABA and GABA can be converted back into glutamate

Answer 184

○ GABAA receptors - ion channels | ○ GABAB receptors - G-protein-coupled

Answer 185

* Relatively common - 400 000 in AUS | * Seizure - sudden excessive activity in neurons (can cause muscle convulsions but not always)

Answer 186

• Epilepsy is a neurological disorder characterised by seizures ○ Believed to be caused by abnormality of GABA neurons and/or in GABA receptors

Answer 187

○ Generalised seizure - Widespread and involve most of the brain ○ Partial seizures - Definite focus and restricted to small part of the brain - Often a scarred region caused by injury or developmental abnormality - common after brain trauma - Simple □ Can cause changes in consciousness (altered sensory, autonomic responses etc) but not loss of consciousness - Complex □ Lead to loss of consciousness

Answer 188

○ 3% of children under 5 have seizures associated with high fevers - Most don't go on to have epilepsy ○ Genes have been linked to epilepsy - Those with the gene generally have first spileptic fit at ~2-3 years old when they get a fever - Majority of genes identified so far control ion channels (which control positive and negative charge of the neuron driving the action potential) - But most seizures are not genetic, and instead are due to abnormal brain tissue and require surgical treatments ○ Vaccination might trigger fever and seizure, but without vaccinations seizures arrive within months anyway

Answer 189

• All of dopamine synthesised in the brain originates either in ○ Substantial Nigra (SN) - In charge of motor control ○ Ventral Tegmental Area (VTA) - Motivation and emotion response - Reward, desire, goal-directed behaviour

Answer 190

• Starts from basic building block - Tyrosine (amino acid found in food) • Tyrosine is converted to DOPA • Dopa is translated into Dopamine • From there, this compound is broken down from dopamine and turned into noradrenaline • Possible to boost the synthesis and generation of Dopamine with drug L-DOPA (increase levels of Dopamine in brain) ○ Artificial synthetic version of DOPA ○ Treated exactly the same way by naturally occurring enzymes ○ Gets converted into Dopamine that is completely indistinguishable from the naturally occurring Dopamine

Answer 191

○ Caused by death and break down of dopamine cells in Substantia Nigra ○ Disease initially characterised by motor tremor, ○ Later sympoms include cognitive impairments and dementia ○ Sympoms often include reduced executive function ○ No cure but symptoms can be reduced through drugs and deep brain stimulation ○ Sometimes treatment of the disease can cause impulsivity, hypersexuality, gambling, addictive behaviours

Answer 192

• If an unexpected reward occurs DA (dopamine) neurons become more active and release a burst of DA • Receiving money is a positive experience (and losing it is negative), but it is jus paper ○ We like money because we associate it with items of activity or value ○ If the gain or loss is unexpected, the feelings associated with that are more intense

Answer 193

○ Monkeys would be given some juice as a 'reward' ○ When that happened - at that time there was a large spike in DA ○ Started to give a beep and then the juice reward ○ Found that after many trials (so that the animal was expecting the reward after the beep), the dopamine burst happened straight after beep, not when reward came ○ The dopamine release does not represent the actual signal (being presented with juice), but represents how good something is relative to what was expected - DA only peaks at the beep, when the actual reward comes the dopamine levels are no higher than usual - no addition dopamine released for the actual reward ○ If the beep is given with no reward - DA burst at the beep, and a few milliseconds later, when reward was expected to come, there is a suppression of neuron activity □ Reflects that outcome is worse than expected

Answer 194

○ Real (eg food and sex) ○ Symbolic (eg money) ○ Virtual (eg points in a game) • DA is involved in all cases

Answer 195

• It is currently unclear why attention and cognitive tasks are 'effortful' and why task engagement is aversive (our brains are also very active when we relax or watch TV) • The feeling of cognitive effort seems particularly linked to working memory and cognitive control • It is proposed that DA codes both goal reward and effort costs and that the aversive feeling of cognitive effort reflects 'opportunity cost' ○ If you're doing one thing, it is at the expense of doing something else • Task persistence is justifiable only while progress outpaces accruing costs • For an animal/human to be successful in life, they need to have balance of task persistence being maintained only while progress towards a positive outcome is being made • Dopamine is released as you make progress ○ The cost of engaging in a particular thing becomes greater the more time you spend on that thing - The longer you stay engaged in a particular task, the more opportunity lost doing other things ○ Make sure you have incentives along the way - increase dopamine, and reduce the likelihood of disengaging ○ As long as there is a signal of progress/incentive, It makes sense to keep going

Answer 196

○ Unpredictability adds to the boost of DA (reward prediction error) ○ If you predictably lose 70% of your money every bet, it would not be addictive ○ If you have unexpected large wins (but still losing an average of 70%), the wins are coded as extremely positive - Disproportionately good compared to boring losses

Answer 197

○ A chronic relapsing disorder which consists of a compulsive pattern f drug seeking and drug taking behaviour ○ Not about the volume of the drug being taken, but the extent to which the behaviour takes place at the expense of other activities and the behaviour persists despite the adverse consequences

Answer 198

§ Cocaine § Amphetamine § Methylphenidate (Ritalin)

Answer 199

□ Blocks reuptake of DA into presynaptic neuron - When normal DA is released, and you're taking cocaine, there's much more dopamine available in the synapse - whatever the downstream messages are that code for positive outcomes, that signal is much stronger - positivity is much higher

Answer 200

□ Ice (pure) and speed (less pure) □ Reverses uptake transporter actively expelling DA and NA (noradrenaline) out of the neuron - Prevents reuptake - Also adds additional dopamine into synapse - Boosts dopamine signal for postsynaptic neuron

Answer 201

□ Dopamine and noradrenaline reuptake inhibitory □ Treatment for ADHD □ Has much slower time course than amphetamines □ Pairing of tablet with change in brain-state don't get associated with one another - not addictive

Answer 202

□ Normal response - When reward is expected no additional dopamine is released (ie only when the beep occurs, not when the actual reward comes) □ Addictive drug response - Addictive DA drugs are always coded by the brain as better than expected ◊ DA reward response always follows the cue ◊ DA is released at the cue AND at the actual reward

Answer 203

○ In animals, if they push on a lever and it releases heroin/opioids, the animal will push the lever until it dies - Will consistently choose lever over food until it starves to death ○ If animals press a button and their dopaminergic reward system is electrically stimulated, they will self-administer this electric shock until they die

Answer 204

• While there is a strong link to DA function and addiction, some drugs cause addiction with relatively less involvement of DA ○ Possibly depending on opioid system • DA might be more important in the behaviour/habit and cognitive control aspects than the pleasant feeling

Answer 205

• 1st problem ○ Drugs initiate a 'wanting' in addicted people - Leads to drug urges or cravings • 2nd problem ○ Cognitive (top-down) control is reduced by impaired function of the prefrontal cortex (PFC) caused by excessive dopamine - Failure of top-down control and rational part of the brain - not failure of thought porcesses, but failure of logical brain having control over behaviours - Imagining studies show PFC abnormalities • Final result -addictive behaviour ○ Failures of top-down control would contribute to loss of control over the urge to take drugs

Answer 206

* Cases of addiction exist for most things that are rewarding (symbolic, real, and virtual) * More individual differences in susceptibility compared to drug addiction